The Influence of Psychological Intervention upon Psycho-Neuro ...

T h e In fl u en ce o f Psy ch o l og i ca l In t e r v e n t i o n u p o n
P s y c h o-Ne u r o-End o c r i o-Immu n n e N e t w o r k
A t h e s i s s u b m i t t e d f o r t h e a w a r d o f
D o c t o r o f P h i l o s o p h y ( P h . D . )
I m p e r i a l C o l l e g e , F a c u l t y o f M e d i c i n e , L o n d o
Aki r a NA ITO M.D.
A u g u s t 2 6 0 0
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F a c u l t y o f M e d i c i n e
D i v i s i o n o f N e u r o s c i e n c e a n d M e n t a l H e a l t h
Cha ri ng Cr oss C a mp u s
S t . D u n s t a n ’ s R o a d , L o n d o n W 6 8 R P
and
D e p a r t m e n t o f I m m u n o l o g y
C h e l s e a a n d W e s t m i n s t e r C a m p u s
3 6 9 F u l h a m R o a d , L o n d o n S W 1 0 9
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T h i s t h e s i s i s d e m d i y c f a th t e r d : t o
N a g a y o s h i N A I T O
1 9 4 0 - 2 0 0 6
M y r o l e m o d e l a n d m e n t o r
w h o t a u g h t m t h e i mp o rt a n c e o f b e i n g m y se l f
a n d p a s e d a w a y a t t h e e n d o P f h . m D y . c o u . r s e
I t han k hi m f o r h i ts rut hf uln e ss, wa rm un de rstan din g and sp i ri tu al sup po rt .
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- 2 -

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
P h . D . a t U n i v e r s i t y o f L o n d o n
A b s t r a c t
A gr owi n g b od y o f e vi d en ce s u gges ts th at th ere are cr os s regu lat or y in flu en ces b etween
t h e p s y c h o l o g i c a l , n e u r o l o g i c a l , e n d o c r i n o l o g i c a l a n d i m m u n o l o g i c a l d s to y s t e m s . T h i s h a s
t h e p r o p o s a l o f a -n e p u s r y o-e c h n o d o c r i o-i n mmu n e n et wo rk, in wh ich a ch an ge in o n e p art h as
con s eq u en t i al i n fl u en ces u p on oth er p arts of th e n etw or k. Th u s p s ych olo gical s tres s can als o
a f f e c t p h ys i c a l w e l l-b ei n g t h rou gh th e n et wor k.
T h i s t h e s i s i s ed b a on s th e h yp ot h es is th at th e d etrimen tal ef fects o f s tres s u p on th e
n etwork can b e al l evi at ed b y p s ych olo gic al in terven tion . Th e aim of th is p roject i s to ex amin e
wh eth er l earn i n g an d p ract i s in g s t r e s s-ma n agemen t s kills i mp ro ves p s yc h o l o g i c a l a n d p h ys i c a l
w e l l -b e i n g.
An i n v i sv tu o d y u s in g u n ivers it y s tu d en ts con firm ed th at e x a m i n a t i s tres o n s p ro vo kes
an xiet y an d in creas es s tres s , an d t h a t s tre s s p ercep tion was as s ociated with N K -c e l l f u n c t i . o n
Immu n e al t er at i on s w e re ob s er ved in vitr o wh en N K -cells an d lymp h o c ytes w ere e xp os ed to
s tres s h orm on es . A n o t h e r i n v i v s o t u d y -in u fect s i ed n p a g t i e n t s H n I o t V r e c e i v i n g a n t i-ret ro viral
t r e a t m e n t s c o n f i r m e d t h a t t h e -ly r m e p h i o c s y t e cou a n t s , t a ne d a th d at y th is d e c l i n e i n
d e c l i n e w a s a s s o c d i a w t i e t h l d i e n c e s in q u a l -o i t f -l y i f e s c s o . r e
T h e ps y c h o l o g i c a l i n t e s r u v s e n d t i n o n t h e p r o j e c t , s -h e l yp f n os is an d J oh rei , a i m e d t o
p r o v i d e a l t e r n a t i v e p e r s p e c t i v e s o f , a n d u n i q u e -h s elp e l f cop in g s trat e gi es f or, s t res s fu l life
even ts . Th es e, p art icu larl y J oh rei , w e r e n s t o h o a l w l e v i o a r t e v e n t o r e v th e r s e ffect e s of s tres s
u p o n t h e , i m n c m l u d n i a e n g d e c s r e y a s e N t -c K i e n l l s m i n u n i v e r s i t y s t u d e a n n t d s the
d e c l i n e o -l f y m p C h D o c 4 y t e T s i n -i H n I f e c V t e d p a t i e . n Ne t s i t h e r i n t e r v af e f n e c t e i d o sn tres s
p e r c e p t i o s n i g n i f i n c t a l , y alth ou gh J oh rei a p p e a r e d to i m p r o v e t h e q -o u a f -l l i t f e y s c s. o r e
T h e s e f i n d i n g s s u p p o r a t p r t i o h r e i h yp ot h es is th at p s ych ol o gical in ter ven tion ma y
cou n teract th e d et ri men tal e ffects of s t res s on h e a l t an h d p r o m o t e w e l l -b e i n g, an d s u gges t th is
v i e a n i n m g-f o c u s e d c o p i n g . T h e w s a e r r a n t t n e h e d f o r f u r t h e r r e s e a r c h t o e x p l o r e t h e i -n
t e r
d ep end en t rel at ion s h ip s a m o n g s t th e in tegrated p s y c h o-n e u r o-e n d o c r i o-i n m m u n e n e t w , o an r k d
t h e i n f l u e n c e o f J o h r e i u p o .
n t h e n e t w o r k
- 3 - I m p e r i a l C o l l e g e L o n d o n

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
C o n t e n t s P a g e
Ab s t r a c t 3
Lis t of F i g u r e s 6
Lis t of T a b l e s 9
Lis t of T e xt bo x e s 14
A b b r e v i a t i o n s
A c k n o w l e d g e m e n t s 16
C h ap ter I I n t r o d u c t i o n
Cont ent s o f c h apte r I 18
1.1 P r o j e c t o v e r v i e w
1.2 T h e o r e t i c a l f r a m e w o r k
1.3 A p p r o a c h t a k e n
C h ap ter II M a t e r i a l s a n d M e t h o d s
C h a p t e r I I I R e s u l t s
Contents o f c h apte r I I 51
2.1 Pa r t i c i ts p a w n i t h r e g a r d t o o u t c o m e s a n d m e a s u r e m e n t t i m e p o 53 i n t s
2.2 P s y c h o l o g i c a l i n t e r v e n t i o n
2.3 S e l f-r e p o r t u e s q t i o n n a i r e s
2.4 M a t e r i a l s a n d m e t h o i d n s v i t r o
2.5 S t a t i s t i c a l a n a l y s e s
C o n t e n t s o f c h apte r I I I 79
3.1 T h e i n f l u e n c e o f p s y c h o l o g i c a l i n t e r v e n t i o n u p -re o n la s te t d r e cs ha s nge s
i n u n i v e r s i t y s t u d e n t s f a c i n g a c a d e m i c e x a m i n a t i o n s
3.2 T he inf lu e nc e of p s y c h o l o g i c a l i n t e r v e n t per i o ce n ive u d p o s n t r e s s and
q u a l i -of-l t y i f and e various imm u n o l o g i c a l d i s -as e a s se oc ia t ed
p a r a m e t e -i r n f s e c t e d i n d i v i H d I u a l V s
3.3 I n v i t inve r o s t iga t io n int o the e ff e ct of e xp os ur e t o st re s s hor mo ne s
u p o n N a t u r a l K i l l e r c e l l s
3.4 I n v i t inve r o s t iga t io n int o the e ff e ct of e xp os ur e t o st re s s hor mo ne s
upon T-l y m p h o c y t e s 151
P h . D . a t U n i v e r s i t y o f L o n d o n
- 4 - I m p e r i a l C o l l e g e L o n d o n
15
19
22
49
60
63
65
77
83
102
128

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
C h a p t e D r i s c I u s V s i o n
Cont ent s o f c h apte r I V 171
4.1 T he in f lu e nc e of ps yc hologic a l in t e r ve n t io n up o n s us ta in e d s tr e ss a nd
s t r e s s-a s s oc ia te d c ha nge s in unive rs it y s t u de nt s f a c in g e x a ms a n d in
p a t i e n t -i s n f e w c i t i t o n h H I V
4.2 S t r e s s ho r mone as s oc ia te d c ha nge s i n v i t i n r o i m m u n e c e l l as n a s
e x e m p l a r of t he p s y c h o-n e u r o-e n d o c r i -i n o m m u n e n e t w i o r n t k e r a c t i 190 o n
4.3 C o n c l u s i o n
4.4 F u t u r e d i r e c t i o n s
R e f e r e n c e s 200
A p p e n d i c e s
A-1. E t h i c s a p p r o v a l , i n f o r m a t i o n 214 s h e e t a n d
A-2. P s y c h o l o g i c a l t r a i n i n g i n t e r v e n t i o n p r o t o c o l s
A-3. Q u e s t i o n n a i r e s
i . S e l f h y p n o s i s t r a i n i n g
i i . J o h r e i t r a i n i n g
S t r e s s p e r c e ( p St Ti AI o n , I E S a n d P ) S S
287
Qu a lit y o f L i fe a nd s leep qu a lit y ( L o , C MCS and P S Q I ) 290
A-4. S t a n d a r o d p e r a t i n g p r o c e d u r e s (S O P s ) f o r l a b o r a t o r y m e t h o d s
[ 3 H ] -t h y m i d i n e i n c o r p o r a t i o n u s i n g w h o l e b l o o d f o r p r 296 o l i f e r a t i o n a s s a y
F lo w c yt o me t r y a na l ys is o f p r o li f e r a t io n r e s p o ns e in w ho le b lo o d a s s a y p r o t o co l
N K c e l l c y t o t o x i c a c t i v i t y a s s a y b y f l o w c y t o m e t r y 300
A-5. P a p e r s 304
i . Pe e r r e v i e w u e b d l i c p a t i o n s
i i . P r e s e n t a t i o n a n d w o r k s h o p g i v e n
i ii . S u p e r v i s o r f o r r e s e a r c h s t u d e n t s
A-6. A d d i t i o n a l r e s u l t s
A-7. R e s e ar c h p r o p o sa l f or p os t-d o ct or i a l p r oj ec t 316
P h . D . a t U n i v e r s i t y o f L o n d o n
173
198
199
227
253
298
304
305
307
226
286
296
308
- 5 - I m p e r i a l C o l l e g e L o n d o n

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Fi gu r e 1 : A t yp i c a l N a t u r a l K i l l e r c e l l
P h . D . a t U n i v e r s i t y o f L o n d o n
L i s t o f F i g u r e s
Fi gu r e 2 : S c h a e o m f t h e -e n e n u d r o c o r i -immun n o e in te ra c t ion
F i g u r e : 3 N u m b e r s o f s t u d e n t s r e c r u i t e d a n d r e m a i n i n g i n t h e -e s t xa u m d y a t t h e E x a m a n d N o
a s s e s s m e n t t i m e p o i n t s . T h e -o n u m t b e s r t u d o e f n t s d r i o s p a l s o d. i n d i c a t e
Fi gur e 4: T i m i n g o f t h e E x a m -e a x n a d m N a o s e n s s m e n t t i m e p o i wit n t s h r e s pe ct to re c ruit me nt for
i n d i v i d u a l s t u d e n t s i n t h e C o h o r t s A a n d B
Fi gu r e 5 : T i m i n g o f t -ups r and a i da n ta-c i o n l l g e c , t i o n f s o e s l s i l o n o s w ( B and a s e l Ex i n ae ms a s se s s ment
points) and nu m b e r s o f tudent s s a t t he s e s s i s o n
Fi gu r e 6 : Timing of t he me as ure me nt c olle ct io n t ime p o i n t s (R e cr u i t m e nt and Af t e r 4 m o n t h s ) a nd the
one-m o n t h b l o c k s (Bas e line , T e r m o n e t o T e r m f o u r ) f o r c l i n i c a l r o u t i n e b l o o d c o l l e c t i o n s
Fi gu r e 7 : T i m i n g o f t w h o e m e a s u r e m e n t p o i n t s Re ( c ruit me nt a n d P o st-i n t e r v tion) e n wit h re ga r d t o t he
pe r iod of t r a in ing a nd pr ac t ice o f t he p s yc h o lo gi c a l i n t e r v e n t i o n s
Fi gu r e 8 : T i m e-p o i n t s ( T r a i n i n g t i m e p o i n t r m a n s d a c t c o h r e d i T n e g t o t h e T r a i n i n . g Inte ) r va ls bet we e n
t h e d o t -l e i n d e s r e p r e s e n t o n e t e r m ( o n e m o n t h )
Fi gu r e 9 : C o m p a r i s o n f or m at w i t h r e g a r d t o t h e T r a i n i n g t i m -i n e t er p ve o i n t i o n ( vs P r . e P os t-
i n t e r ve nt i o n ) . I nt e r va l s be t we e n do t-l i n e s r e p r e s e n t o n e t e r m ( o n e m o n t h ) a s i n F i g u r e 8
F i g u r e : 1 F 0 S C v s . S S C d o t t p l o
Fi gur e 11: I n d i v i d u a l c o r t i s o l l e v e l s l t i u n r e t m h e d i u t m i s a s n u d e i n c u p l a s m a f r o m 3 4 v o l u n t e e r s
4 5 6
Fi gur e 12: K5 62 c e ll gr owt h a t s t a r t i n g c e l l c o n c e n t r a , t 1.5x10 i o n s and o f 1.0x10 1 . 5 x 1 0 c e l l s p e r m L
F i g u r e : 1 A 3 c q u i s i o n s e t t i n g s o f a f l o w c y t o m e t r y m e t h o d m e a s u r i n g t h e l e v e l s o f N K c
Fi gur e 14: Ac quis ion s e tt ings of t h e f l o w c yt o m e ter in t h e N C R a n a l y s e s
Fi gur e 15: Ac quis ion s e tt ings of the f l o w c yt o m e ter i n t Annexin h e V- P I a n a l y s i s
Fi gur e 16: M e a n ( 9 5 % C . I . ) P S S s c o r e -e s xa a m t a nt d h E e xa m N o t i n m e p o i nts
F i g u r e 7: 1 M e a n ( 9 5 % C . I . S ) t a t e a n x i e sc t o y r es in t h e ST AI a t t h Non-e e xa m a n d Ex a m t i m e p o i n ts
F i g u r e 8: 1 M e a n (95% C.I .) NK-c e l l p e r c e n t a g e s i n m a l e a n d f e m a l e s t u d e n t s
F i g u r e 9: 1 M e an ( 95% C.I .) N K C A (% k i l l i n g in ) t he N ot -s t r e s s e a d n d S t r e s s subgroups e d
Fi gur e 20: M e an ( 95% C.I . ) NKCA le ve ls ( % kil lin g) in t he N ot -s t r e s s and e d S t r e s s ma e d le s t u d e n t s
Fi gur e 21: M ea n (95% C.I .) p e r -N K -c e l l c yt o t o x ic ac t ivit y ( c a lc u la te d as a r at io: NK c yt oto xic a ct ivit y
( N K C A ) -c / e l N l K p e r C%) c e ) in n t he a Not-st g e r es s( ed N a K n d S t r e s s subgroups e d
Fi gur e 22: M e an ( 95% C.I .) per-N K -c e l l c y t o t o x i c a c t i v i t y ( -c c e ll a l c u l a t e d a s
p e r c e n t a g e ) in t he N ot -s t r e s s e d a n d S t r m e a s l e s e s d t u d e n t s
F i g u r e 3: 2 M e a n (95% C.I .) C D 4 -c e T l l l e v e ( l % s ) o f m a l e a n d f e m a l e s t u d e n t s
F i g u r e 4: 2 M e a n (95% C.I.) S t a t e a n x i e t y s c o r e s i n t h e S T of A I t he t hr ee gr oups at bas e line a nd the
E x a m t i m e p o i nt
F i g u r e : 2 M 5 e a n (95% C.I .) l e v e l -c e s l l s of o t he f th re e N gr K oups at bas e lin e a nd the E xa m t i m e p o i nt
F i g u r e : 2 The 6 i n d i vi d u a l le ve ls of N K -c e l l p e r c e n t a g t e h s e t i h n r g e e r o u s p a t ba s e lin e a nd t he Exa m
t i m e p o i n t
- 6 - I m p e r i a l C o l l e g e L o n d o n

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
F i g u r e : 2 M 7 e a n (95% C.I .) l e v e l s -c o e f l l s of C tD he 4 t hre T e gr oups at ba s e lin e and the Ex a m t ime
point
Fi gur e 28: The i n d i vi d u a l l e v e l s -c o e f l l C D p e 4 r c e T n t a g t e h s e t i h n r g e e r o u s p a t b a s e l i n e Exa a n m d t h
t i m e p o i n t
F i g u r e : 2 M 9 e a n (95% C.I .) l e v e l s -c o e f l l s of C tD he 8 t hre T e gr oups at ba s e lin e and the Ex a m t ime
point
F i g u r e : 3 The 0 i n d i vi d u a l l e v e l s -c o e f l l C D p e 8 r c e T n t a g t e h s e t i h n r g e e r o u s p a t ba se lin e a nd t he Exa m
t i m e p o i n t
F i g u r e : 3 M 1 e a n (95% C.I.) P S S l e v e l of s t he N ot -st re sse d a nd S t r e s s subgroups e d a t r ec r uit me nt and
f o u r m o n t h s l a t e r
F i g u r e : 3 M 2 e a n (95% C.I .) le ve ls of t he St at e a nx iet y s c or es in th e ST AI of t he N ot -s t r e s s and e d S t r e s s
subgroups at re c ruit me nt a nd f o u r m o n t h s l a t e r
F i g ure 33: M e a n (95% C.I .) le ve ls of t he I ES in t he Not-s t r e s s and e d S t r e s s ub gr oups a t r e cr uit men t and
f o u r m o n t h s l a t e r
F i g u r e : 3 M 4 e a n (95% C.I .) le ve ls of t he Lo C in t he N ot -s t r e s s and e d S t r e s s subgroups e d a t r e cr uit ment
and f o u r m o n t h s l a t e r
F i g u r e : 3 Mean 5 (95% C.I .) le ve ls of t he M SC in t he N ot -s t r e s s and e d St re s se d subgroups at re cr uit me nt and f o u r m o n t h s l a t e r
F i g u r e : 3 M 6 e a n (95% C.I .) le ve ls of t he P SQI in t he S t r e s s and N ot -s t r e s s subgroups e d a t r e cr uit ment
and f o u r m o n t h s l a t e r
Fi gu r e 3 7 : M e a n ( % 9 5 C. I .) C D 4 gr a d i e nts ( c e l l per s l pe r mo nt h) in the I n c r e a se d co n t r ol ( de cr e as ed
s c o r e s o f t h ) e a n d L D o e C c r e a s c e on d t r o l ( i n c r e a s s c o e r d e s o f t h ) e subgroups L o C
Fi gu r e 3 8 : M e an ( 95 % C. I .) C D 4 gr a d i e nts ( c e l l per s l pe r m o n t h ) i n It mpr h e ove d ps yc hologic a l
functioning (I m p r o v e d : Q o c i r L e n a s e d s c o r e s of the M C S ) and De c re a se d ps yc ho lo gic a l
functioning (D e c r e a s e d : Q o d e L c r e a s c e o r d e s of t he MCS ) s u b g r o u p s
Fi gu r e 3 9 : M e an ( 95% C.I .) CD 4 gr a d i e nts ( c e l l per s l pe r m o n t h ) i n It mpr h e ov e d s le e p qualit y
( d e c r e a s e d s c o r e s o f t h P e S Q I ) and D e c r e a s e d s l e e p q u a l ( i t i y n c r e a s c s o e r d e s of t he P S Q I )
subgroups
F i g u r e 0: 4 M e a n s ( 9 5 % C . I . ) C D 4 g r a d i over e n t s t h e f i v e m o n t h st s udy p e r i o d f r o m t Ba h e s e lin e t o t he
P os t -i n t e r v e n t i m o e n p o i nt
F i g u r e 1: 4 CD4 g r a d i e n t s o f one c o nt r o l s u bj e ct a t t h e P r e-i n t e rve nt ion and P o st -i n t e r v e n t i o n p e r i o d s
F i g u r e : 4 CD4 2 g r a d i e n t s o f one J o hr e i s ub j e c t a t t h e P r -int e e r ve nt io n a n d P os t-i n t e r v e n t i o n p e r i o d s
F i g u r e : 4 I3 ndivid ua l c ha nge s i n CD4 gr a d i en t s ( ce l l c o un ts pe r l p e r m o ) n in t h t h e S e l f-hypnosis,
J o h r e i and D a t a b a s e-c o n t r o l g r o u p b s e t w e e n t h e P r e-i n t e r v e n t i a n o d n P o st -in t er ve nt ion
periods
F i g u r e : 4 M4 e ans ( 95% C.I.) CD4 gr adie nts (c ou nt pe r l p e r m o ) n in t h t h S e e l f-hypnosis and J ohr e i and
D a t a b a s e-control g r o u p s i n t h e P r e- and Post- i n t e r v e n t i o n p e r i o d s
F i g u r e : 4 ( a) 5 I nd ivid ua l ( b) M e a n ( 9 5 % C . I . N ) K C A le ve ls a t Tim e 0 a n d a f t e r 2 4 h o u r i n c u b a t i o n
P h . D . a t U n i v e r s i t y o f L o n d o n
- 7 - I m p e r i a l C o l l e g e L o n d o n

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
F i g u r e : 4 ( a) 6 I nd ivid ua l ( b) M e a n ( 9 5 % C . I . N ) K -c e l l p e r c e n t a g i e n P B M C s a t T i m e 0 a n o d u rs a f t e r 2 4 h
F i g u r e : 4 ( 7 a ) I nd ivid ua l ( b) M e a n ( 9 5 % C . I . N ) K C A l e v e l wi s t h c o r t i so l at 0, 250 and 2500nM
F i g u r e : 4 ( a) 8 I nd ivid ua l ( b) M e a n ( 9 5 % C . I . N ) K -c e l l p e r c e n t a g wit e h c ort is ol at 0, 250 a n d 2500nM
F i g u r e : 4 C 9 o r r e l a t i o -c n y t b e o t m e w t e e r n y f m e l -r t e o l h w e a o s d i n g a m n e t d o h o f d L D H t h e N K C A
F i g u r e : 5 ( a) 0 I nd ivid ua l ( b) M e a n ( 9 5 % C . I . N ) K C A (50:1) l e v e l (% s k i l l ) i a t n Ti g m e 0 a n d a f t e r 2 4 h r s
F i g u r e : 5 ( a) 1 I nd ivid ua l ( b) M e a n ( 9 5 % C . I . NKCA ) (25:1) l e v e l s (% k i l l ) i a t n Ti g m e 0 a n d a f t e r 2 4 h r s
F i g u r e : 5 P 2 e r c e n t a -c g e ll e in s t o t o a l f a n N d K e a c h s u b s e t a t T i m e 0 a n d a f t e r 2 4 h o u r s i n c u b a t i
F i g u r e : 5 ( a) 3 I nd ivid ua l ( b) M e a n ( 9 5 % C . I . Nkp46 ) (m.f.i.) a t Ti m e 0 a n d a f t e r 2 4 inc h r uba s t io n
F i g u r e : 5 ( a) 4 I nd ivid ua l ( b) M e a n ( 9 5 % C . I . N ) k p 30 (m.f.i.) a t Ti m e 0 a n d a f t e r 2 4 i h n r c s ub a t ion
F i g u r e : 5 ( a) 5 I nd ivid ua l ( b) M e a n ( 9 5 % C . I . N ) K C A (50:1) l e v e l s (% kill ing) o f P B M C s i n c u b wit a t h e d
o r w i t h o u t c l o r t i s o
F i g u r e : 5 ( a) 6 I nd ivid ua l ( b) M e a n ( 9 5 % C . I . N ) K C A (25:1) l e v e l s (% kill ing) o f P B M C s i n c u b wit a t h e d
o r w i t h o u t c l o r t i s o
F i g u r e : 5 M 7 e a n (9 5% C.I .) of the NKCA a t T ime 0 a nd aft e r 24 hr s in cu bat io n of P BM Cs wit h / out 2 5 0 n M c o r t i s o l i n t h e t a r g e t : e f f e c t o r r a t i o o f 2 5 : 1
F i g u r e : 5 C 8 o r r e l a t i o n s b e t w e e n t h e c h a n g e s a n d d i f f e r e n c e s o f t h e N K % C A killin ( g: be t we e n a t T ime 0
a n d a f t e r 2 4 h r b s a t i o n n c u o f P B M C s w i t h / o u t 2 5 0 n M c o r t i s o l i n t h e r a t i o o f 2 5 : 1
F i g u r e : 5 P 9 e r c e n t a -c g e ll e in s t ota l o a nd f e a ch N K s ubs et in th e P BM Cs a ft er 24 ho urs in cu ba t io n wit h
a n d wi t h o u t 2 5 0 nM c or t i s o l
F i g u r e : 6 ( a) 0 I nd ivid ua l ( b) M e a n ( 9 5 % C . I . Nkp46 ) (m.f.i.) a f t e r 2 4 hr s i nc u b at i o n of P BM C s wi t h / o ut
c o r t i s o l
F i g u r e : 6 ( a) 1 I nd ivid ua l ( b) M e a n ( 9 5 % C . I . N ) k p 30 (m.f.i.) a f t er 2 4 hr s i nc u b at i o n of P BM C s wi t h / o ut
c o r t i s o l
F i g u r e : 6 M 2 e a n ( 9 5 % C . I . and ) individual expression of N k p 4 6 ( m . f . i . -c ) e lls o n t h e c y t o
( C D56 dim C D 1 6 + ) a t T i m e 0 a n d a f t er 2 4 hr s i nc u b at i o n of P B M Cs wi t h / o ut 2 5 0n M c o r t i s o l
F i g u r e : 6 M3 ea n (9 5% C.I .) and individu a l le ve l of NKCA a t T ime 0 an d af te r 24 hr s in c uba t io n of
P BM Cs wit h / o ut 250nM c or t iso l a t t a r g e t : e f f e c t o r r a t i o o f 2 5 : 1
F i g u r e : 6 G 4 r ou p s d e f i n e d b y t e r t i a r y s p l i t o f t h e N K C A l e v e l s a f t e r 2 4 h o u r s i n c u b a t i
F i g u r e : 6 M5 ea n (9 5% C.I .) pla s ma le ve ls of c ort is ol in t he High , in t e r me diat e ( M id) a n d Lo w NKC A
le ve l gr o u p s a f t e r 2 4 h o u r s i n c u b a t i o n
F i g u r e : 6 M6 ea n (9 5% C.I .) pla s ma le ve ls of D H E A -S in t he High , in t e r me diat e ( M id) a n d Lo w NKC A
le ve l gr o u p s a f t e r 2 4 h o u r s i n c u b a t i o n
F i g u r e : 6 M7 ea n (9 5% C.I .) pla s ma le ve ls of me la t on in in th e High , in t e r me dia te (M id ) a nd Lo w N KC A
le ve l gr o u p s a f t e r 2 4 h o u r s i n c u b a t i o n
F i g u r e : 6 ( 8 a ) I n d i v i d u a l b) ( M e a n ( 9 5 % C . I . b ) a c k g r o u n d p r o l i f e s r of a t P BM i o n Cs c ult ured
F i g u r e : 6 ( a) 9 I nd ivid ua l ( b) M e a n ( 9 5 % C . I . p ) r o l i f e r a t i o n r e s of p o P n B s e M C s t o t h e P P D a n t i g e n
F i g u r e : 7 ( a) 0 I nd ivid ua l ( b) M e a n ( 9 5 % C . I . p ) r o l i f e r a t i o n r e s of p o Pn BM s e Cs t o t he H e r p e s a nti g e n
F i g u r e : 7 ( a) 1 I nd ivid ua l ( b) M e a n ( 9 5 % C . I . p ) r o l i f e r a t i o n r e s of p o Pn BM s e Cs t o t he SEB a t Da y 3
w i t h / o ut co r t i s o l
P h . D . a t U n i v e r s i t y o f L o n d o n
- 8 - I m p e r i a l C o l l e g e L o n d o n

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
F i g u r e : 7 ( a) 2 I nd ivid ua l ( b) M e a n ( 9 5 % C . I . p ) r o l i f e r a t i o n r e s of p o Pn BM s e Cs t o t he P H A a t Da y 3
w i t h / o ut co r t i s o l
F i g u r e : 7 ( 3 a) I nd ivid ua l ( b) M e a n ( 9 5 % C . I . background ) pe r ce nt a g e s o f C D -c 8 e l T l s e x p r e s s i n g C D 9 5
F i g u r e : 7 ( a) 4 I nd ivid ua l ( b) M e a n ( 9 5 % C . I . background ) pe r ce nt a g e s o f C D -c 4 e l T l s e x p r e s s i n g C D 9 5
F i g u r e : 7 ( a) 5 I nd ivid ua l ( b) M e a n ( 9 5 % C . I . p ) e r c e n t a g e s o f T-c C D e l 8 l s p e r x e s s i n g C D 9 5 i n P H A
s t i m u l a whole t e d blood culture in t he a bs e nc e o f co r t i s o l
F i g u r e : 7 ( a) 6 I nd ivid ua l ( b) M e a n ( 9 5 % C . I . p ) e r c e n t a g e s o f T-c C D e 4 l l s e x p r e s s i n g C D 9 5 i
s t i m u l a whole t e d blood culture in t he a bs e nc e o f co r t i s o l
F i g u r e : 7 7 ( a ) I n ad l i ( v b) i M d u e a n ( 9 5 % C . I . p ) e r c e n t a g e s o f T-c C D e 8 l l s e x p r e s s i n g C D 9 5 i
s t i m u l a whole t e d blood culture in t he p r e se n ce o f c o r t i s o l
F i g u r e : 7 ( a) 8 I nd ivid ua l ( b) M e a n ( 9 5 % C . I . p ) e r c e n t a g e s o f T-c C D e 4 l l s e x p r e s s i n g C D 9 5 i
s t i m u l a whole t e d blood cultur e i t he n p r e se n ce o f c o r t i s o l
F i g u r e : 7 M 9 e a n ( 9 5 % C . I . p ) e r c e n t a g e s o f P H A s t i m u T-c l a et lls e d e xpr C D es 8 s ing CD95 a ft e r
( a ) 2 4 h ou r s , ( b ) 48 h o ur s o f i n cu b at i o n wi t h a n d wi t h o u t c o r t i s o l
F i g u r e : 8 M 0 e a n ( 9 5 % C . I . p ) e r c e n t a g e s o f P H A s t i m u T-c l a e t lls e d e xpr C D es 4 s ing CD95 a ft e r
( a ) 2 4 h ou r s , ( b ) 48 h o ur s o f i n cu b at i o n wi t h a n d wi t h o u t c o r t i s o l
F i g u r e : 8 1 I n d i v i d u a l p e r c e n t a g e s -c e o l f l s a p ( o b -c p ) t e lls o in t C cD i u4 bc at eT d ( 3 a da ) ys wit C D h 8 T
a n d wi t h o u t c o r t i s o l
F i g u r e : 8 ( a) 2 I nd ivid ua l ( b) M e a n C . ( I . ) background 9 5 % pe r ce nt a g e s o f C D -c 8 e l T l s e x p r e s s i n g C D 2 5
F i g u r e : 8 ( a) 3 I nd ivid ua l ( b) M e a n ( 9 5 % C . I . background ) pe r ce nt a g e s o f C D -c 4 e l T l s e x p r e s s i n g C D 2 5
F i g u r e : 8 ( a) 4 I nd ivid ua l ( b) M e a n ( 9 5 % C . I . p ) e r c e n t a g e s o f T-c C D e 8 l l s e x p r e s s i n g C D 2 5 i
s t i m u l a whole t e d blood culture in t he a bs e nc e o f co r t i s o l
F i g u r e : 8 ( a) 5 I nd ivid ua l ( b) M e a n ( 9 5 % C . I . p ) e r c e n t a g e s o f T-c C D e 4 l l s e x p r e s s i n g C D 2 5 i
s t i m u l a whole t e d blood culture in t he a bs e nc e o f co r t i s o l
F i g u r e : 8 ( a) 6 I nd ivid ua l ( b) M e a n ( 9 5 % C . .) I p e r c e n t a g e s o f T-c C D e 8 l l s e x p r e s s i n g C D 2 5 i
s t i m u l a whole t e d blood culture in t he p r e se n ce o f c o r t i s o l
F i g u r e : 8 ( a) 7 I nd ivid ua l ( b) M e a n ( 9 5 % C . I . p ) e r c e n t a g e s o f T-c C D e 4 l l s e x p r e s s i n g C D 2 5 i
s t i m u l a whole t e d blood culture in t h e p r e s e n f c e o r t o i s o l
F i g u r e : 8 M 8 e a n ( 9 5 % C . I . p ) e r c e n t a g e s o f P H A s t i m u T-c l a et lls e d e xpr C D es 8 s ing CD25 a ft e r
( a ) 2 4 h ou r s , ( b ) 48 h o ur s o f i n cu b at i o n wi t h a n d wi t h o u t c o r t i s o l
F i g u r e : 8 M 9 e a n ( 9 5 % C . I . p ) e r c e n t a g e s o f P H A s t i m u T-c l a et lls e d e xpr C D es 4 s ing CD25 a ft e r
( a ) 2 4 h ou r s , ( b ) 48 h o ur s o f i n cu b at i o n wi t h a n d wi t h o u t c o r t i s o l
P h . D . a t U n i v e r s i t y o f L o n d o n
L i s t o f T a b l e s
T ab l e 1 : C l a s s i f i c a t i o n o f t h ma e in c ompo ne nt s of t h e i m m u n e s y s t e m
T able 2: C D e x p r e s s -c ei lls o a n d lymphoc b y yt N e s
K
- 9 - I m p e r i a l C o l l e g e L o n d o n

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
T ab l e 3 : D e f i n i t i o n s o f v a r i o u s e n d o g e molec n o u s ule s
T able 4: N u m b e r a n d p e -i r c n f e n c t a e d g e i n o d i f v i H d I u a V -c l es ll c ou w nh ts o c he h c a t d t he C D 4 T
m o n t h l y t i m e p e r i o d s f r o m t h e R e c r u i t m e n t t o f o u r m o n t h s a f t e r t h e r e c r u i t m e n t ( T e r m 4 )
T ab l e 5 : N u m b e r an d m o nt h of su b j e ct s wh o st a r t ed a nt i-r e t ro vir a l me d ic a t io n a n d d r op p e d f rom t he
s t u d y ( N B : T e r m X r e p r e s e n t s t h a t X m o n t h s a f t e r t h e R e c r u i t m e n t t i m e p o i n t )
T ab l e 6 : M e a n p e r c e n t a g e s a n d c o u n t s ( s t a n d a r d d e v i a t i o n : S of D N ) K -c e l l s, C D 4 and C D 8 T-c e lls and
t ota l lymp ho c yt e c ount s u s i n g a s i n lunt g l e e r v o ( 9 t ube s colle c t ed a nd a ve r a ge d on th r ee
s e p a r a t e o c c a s i o n s )
T able 7: M e a n ( 9 5 % C . I . ) P S S s c o r e -e s xa a m t and t h E e x a N m o n t i m e p o i n t s
T able 8: M e a n ( 9 5 % C . I . ) S t a t e a n x i e t y s c o r e s i n -e xa t m h e and S T E A x a I m a t i m t e h p e o i n N t o s n
T able 9: M e an ( 95% C.I .) N K -c e l l p e r c e n t a g e s i n m a l e a n d f e m a l e s t u d e n t s
T able 10: M e an ( 95% C.I .) l e v e l s o f N K C A ( % k i l l i n i g n ) the N ot -s t r e s s and e d S t r e s s s e d u bg r o u p s
T able 11: M e a n ( 95% C.I .) le ve ls of NKCA ( % killin g) in t he N ot -s t r e s s and e d S t r e s s e m d a l e s t u d e n t s
T able 12: M e a n ( 9 5 % C . I . ) r -c a et ll in i t ho e s N ot -s o tr ef ss e d and N K C S A t r e t s s o s e t d u d e N n K t s
T able 13: M e a n ( 9 5 % C . I . ) r -c a et ll in i t ho e s N ot -s o tr ef ss e d and N K C S A t r e t s s o m e a d l e N s K t u d e n t s
T able 14: M e an ( 95% C.I .) C D 4 -c T e l l l e v e l s ( % ) o f m a l e a n d f e m a l e
T a ble 15: T h e n u m b e r s o f p a r t i c i p a n t i n t h e t h r e e g r o u p s -hypnos ( S e l f is , J oh r e i and Re la xa t io n c ont ro l)
in the N ot -s t r e s s e d a n d S t s r u e b s gr s o e up d s bas e d on t he P SS s c o r es at t he E xa m t i m e p o i nt
T able 16: M e an ( 95% C.I .) S t a t e a n x i e t y s tc he o r S e s l f-hypnos i n is , J ohr e i and Re la xa t io n c ont r ol groups at b a s e l i n and e t h e Ex a m t i m e po i n t
T able 17: N u m b e r s o f p a r t i c i p a nt s i n t h e t hr e e gr o u p s a t t h e Ex a m t i m e p o i n t
T able 18: M e an ( 95% C.I .) l e v e l -c s e l l o f ( % t he ) N S K i e l n f-h yp no s is , J ohr e i and Re la xa t io n c ont ro l
groups at b a s e l i n and e t h e Ex a m t i m e po i n t
Table 19: P e r c e n t a g e s ( n u m b e r -c es ll c) ou nt s o ma f int a ine s u d or b j inc e re ac se t d s w h o s e N K
(Ma i n t a i n ) e a d n d d e c r e a s e d (D e c r e a s e ) d i n t h e S e -hypnosis l f and Johrei and Re la xat io n
c o n t r o l g r o u p s f o r t h -t e o-t I r n eat t e an n at lys i o is n ( mis s ing da ta we r e ad de d int o t he nu mb er in
t he D e c r e a s e group) d
T able 20: M e an ( 95% C.I .) l e v e l s o -c f e l l C D 4 ( % ) t T h e S i e n l f-hyp no s is , Johre i a nd Re la xat io n c on tr ol groups at b a s e l i n and e t h e Ex a m t i m e po i n t
T able 21: M e an ( 95% C.I .) le ve ls o f C D -c 8 e l T l ( % t he ) S i e l n f-h yp no s is , Johre i a nd Re la xat io n c on tr ol groups at b a s e l i n and e t h e Ex a m t i m e po i n t
T able 22: M e dia ns , me ans and st an dar d de via t io ns of t he P SS of t h e u n i v e r s i t y s t u d e -e n xa t s m a t n o n
a nd e xa ms an d of t h e -i n H f I e c V t individuals e d a t rec r uit me nt a nd f o u r m o n t h s l a t e r
T able 23: M e an ( 95% C.I .) l e v e l s o f t h e the P S N S ot -s i t n r e s s e d a n d S t subgr r e s s oe ud ps at t he
r e cr u i t m e nt and f o u r m o n t h s l a t e r
T able 24: M e d i a n , m e a n a n d s t a n d a r d d e v i a t i o n o f a n t x i h e t S y t a s t c of o e r t e h e u n i ve r s i ty s tude nt s a t
non-e xa m an d e xa ms and of t h e -i n H f I e c V t individuals e d a t rec r uit me nt a nd f o u r m o n t h s l a t e r
T able 25: M e an ( 95% C.I .) l e v e l s o f t h e S t a t e a n x i e t y s c o the r e Not-st o f rt es h se e d S a T n d A I S t i r n e s s e d
subgr ou ps at t h e r e cr u i t m e nt and four months l a t e r
P h . D . a t U n i v e r s i t y o f L o n d o n
- 1 0 - I m p e r i a l C o l l e g e L o n d o n

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
T able 26: M e an ( 95% C.I .) l e v e l s o f t h e the I subgr E S i ou n ps of t he N ot -st re s se d and S t r e s s at e d t he
r e cr u i t m e nt and f o u r m o n t h s l a t e r
T able 27: M e an ( 95% C.I .) l e v e l s o f t h e t he L o N C ot -s i tr n es s ed a nd S t r e s s subg e d r o u p s a t t he
r e cr u i t m e nt and four m o n t h s l a t e r
T able 28: M e an ( 95% C.I .) l e v e l s o f t h e the M C N S ot -st i re n ss e d and S t r e s s subgr e d ou ps at r e cr u i t me n t
and f o u r m o n t h s l a t e r
T able 29: M e an ( 95% C.I .) l e v e l s o f t h e t he P S Q N I ot -s i t n r e s s and e d S t r e s s subgr e d ou ps at r e cr u i t me n t
and four months l a t e r
T able 30: C o r r e l a t i o n b e t w e e n t h e C D 4 g r a d i e n t pe ( r c e l pl es r m o n t h ) a n d t h e c h a n g e s c o r e s o f
p e r c e i v e d q u a -of-l l i t i f y e s c a l e s
T able 31: M e an ( 95% C.I .) C D 4 -c T e ll c han ge ove r t he f ive mont h (c e lls per l p e r m o -n
t h ) i n H I V
inf e ct e d in dividua ls of t he I n c r e a s e c d o nt ro l a n d De cr e as e d c ont r ol subgroups
T able 32: M e an ( 95% C.I .) C D 4 -c T e ll c han ge ove r t he f ive mont h (c e lls per l p e r m o -n
t h ) i n H I V
inf e ct e d in dividua ls of t he I m p r o v e QoL d a nd D e c r e a s e d subgroups Q o L
T able 33: M e an ( 95% C.I .) C D 4 -c T e ll c han ge ove r t he f ive mont h (c e lls per l p e r m o -n
t h ) i n H I V
i n f e ct e d in dividua ls of t he I m p r o v e d s l e e p q u a l and i t y D e c r e a s e d s l e e p q u a l subgroups i t y
T a b l e 34: M e an ( 95% C.I .) l e v e l s o f t -i n h d i e v i d u a I l s E i S n t h e i S -hypnosis, n e l f t h e Johrei H and I V
Control groups a t t h e B a s e l i and n e P o st -i n t e r v e n t i o n t i m e p o i n t s
T able 35: S u m m a r y o f t h e n u m b e r -i s n d i v i ( d u p a l e s r w h c o s e n c h t a n g a in e s g t he e LoC s ) o f t h e H I
b e t we e n t h e Ba s e l i n e a n d po s t-in te r ve nt io n e it h er d ec re a se d ( Ga in e d s e n se of c on tr o l) or
i n c r e a s e d ( L o s t s e n s e o f c o n t r o l ) i n t h e -h S e y l p f n o s i s , J o h r e i a n d C o ps n t r o l g r o u
T a b l e 36: S u m m a r y o f t h e n u m b e r -i s n d i v i ( d u p a l e s r w h c o s e n c h t a n g a in e s g t he e Ms CS ) o f t h e H I
b e t we e n t h e Ba s e l i n e a n d po s t-in te r ve nt io n e it h er in c re a se d ( I mpr o ve d me nt a l q ua lit y o f lif e )
o r d e c r e a s e d ( D e c r e a s e d m e n t a l q u a l i t y o f l i f e ) i n t h -hypnos e S e l f is , J oh re i a nd Contr ol
groups
T a b l e 37: S u m m a r y o f t h e n u m b e r -i s n d i v i ( d u p a l e s r w h c o s e n c h t a n g a in e s g t he e Ps SQI ) o f t h e H I
b e t we e n t h e Ba s e l i n e a n d po s t-in te r ve nt io n e it h er d ec re a se d (I mp ro ve d s le e p q u a lit y) or
i n c r e as e d ( D e cr ea s ed s l e ep q ua l i t y) i n th e S e l f-hypnosis, Johrei and Control groups
T able 38: M e an ( 95% C.I .) le ve ls of C D 4 gr ad ie nts (c o u n t s per l per month) i n H I -inf V e c te d
i n d i v i d u a l s i n t h e S -hypnosis, e l f J o h r e i and Control groups
T able 39: P er ce nta ge s (number s) o f p a r t i c i p a n t -c s e ll cw oh un o ts s ma e inta C D ine 4 d or T de c re a se d ove r
t he f ive mo nt hs in t h e S e l f-h yp n o s i s a n d J o hr e i and C o nt r o l groups f o r t h e I n t e -t n t o-t i r eat o n
a na lys is ( mis s ing da t a we r e a d d e d i n t o t h e n u m t b e h r e D i e n c r e group) a s e d
T able 40: M e an ( 95% C.I .) le ve ls of C D 4 -ce T l l (c o u n t s per l) i n H I -inf V e ct e d in dividua ls in t he
g r o u p s o f t h e S e -hypnosis, l f J oh r e i and D a t a b a s e-c ont ro ls a t t h T e r a i n i n g p e r i o d
T able 41: M e an ( 95% C.I .) C D 4 gr a die nt s i n -individuals H I V in the S e l f-hypnos is , J ohr e i a nd Da ta bas e
control gr ou ps , a nd i n a l l the 96 in d i v i d u a l s ( A L L ) a t -i t h n e t e P r v e e n t i o n p e r i o d
P h . D . a t U n i v e r s i t y o f L o n d o n
- 1 1 - I m p e r i a l C o l l e g e L o n d o n

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
T a b l e 42: P e r c e n t a -i g n e d i v s i d u a l o s f i n t h H e I S -h e V l y f p n o s i s , J o hr e i a n d D a t a b as e co n t r o l g r o u p s
w h o s e c h a n g e s i n C D 4 g r a d i e n t s b e t w e e n -i t n h t er e ve P n r t e i o n a n d P os t-inte r ve nt io n per io ds
w e r e e i t h e r i n c d r , e a s e t a y e d t h e s a m e o r w i d t e h c r a e a j s u e d g e m e n t t h a t a of c fh our a n g oe f
l e s s c e l l pe s r l pe r mo nt h wa s de f ine d a s t h e s a m e c h a n g e ( S t a y e d t h e s a m e s u b g r o u , p mor ) e
t h a n f o u r i n c r e a s ( e I m p r o v i n g s u b g r o u p ), a nd m o r e t h a n f o u r d e c r e a s e ( W o r s e n i n g s u b g r o u p )
T a b l e 43: M e an ( 95% C.I .) C D 4 gr a die nt s i n -individuals H I V in the S e l f-h y p n o s i s , J o h r nd e i Da a ta bas e
control g r o u p s at t h e P r -i e n t er ve n t i o n an d P ost-i n t e r v e n t i o n p e r i o d s
P h . D . a t U n i v e r s i t y o f L o n d o n
Ap p e n d i x 6
T able A-1: M e an ( 95% C.I .) P SS le ve ls of t h e C o h o r t s A and B a t t h e -exam N o n and E x a m t i m e p o i n t s
T able A-2: M e an ( 95% C.I .) St a te a nx ie t y le ve ls of the Cohorts of A and B a t t h e -exam N o n and Exa m
t i m e p o i n t s
Ta b l -3: e M A e a n ( 9 5 % c y t C o t . o x I i c a . c t ) i v i t N y K i Cohorts n t h e A a n d B a t Non-e t h e x a m a n Exa d m
t i m e p o i n t s
T able A-4: M e a n ( 9 5 % -c e ll C p . e r c I e n . t a g ) e s in the N K C o h o r t s A a n d B a t t h -e e x a N m o n a n Exa d m
t ime points
T able A-5: M e a n ( 9 5 % C . -c I e . l ) l e r p C c D 4 e n T t a g e s i n t at h the e Non-ex C o h ao m r at nd s A a n d B
E x a m t i m e p o i n t s
T able A-6: M e a n ( 9 5 % 8 T-c C e. ll pI e rc . e nt ) a ge s C in D the Cohor ts A and B at the Non-ex a m a nd
E x a m t i m e p o i n t s
Table A-7: M e a n ( 9 5 % C A . I l e . v e ) l s a N t K -e t xa h e m and N o n E x a m t i m e p o i n t s
T a b l e A-8: M e a n ( 9 5 % -c C . e l I l . ) a n d N K C D 4 -c a e l n l d ( C % D ) 8 a T t -e t xa h m e and N o n Ex a m t ime
points
T a b l e A-9: Numbe r of st ude nts in th e N ot -s tr e ss e d and S t r e s s se ubgr d ou ps wit h r e g a r to d gender who
f i l l e d i n th e P S S a n d h a d b l o o d c o l l e c t i o n f o r l a n y d m p N h K o c C y A t e l e v e l a n a l y s e s
T able A-10: M e an ( 95% C.I .) N K -c e l l p e r c e n t a the g e s Not-s i n tr e ss e d and S t r e s s subg e d r o u p s
T able A-11: M e a n ( 9 5 % -c C e. ll pe I r. ce nt ) a ge s N in K the Not-s tr e ss e d and S t r e s s m e d a l e s t u d e n t s
T able A-12: M e a n ( 9 5 % -c C e. ll pe I r. ce nt ) a ge s N in K the Not-s t r e s s e a d n d S t r e s s f e m d a l e s t u d e n t s
T a b l e A-13: M e a n ( 95% C.I .) le ve ls of NKCA ( % killin g) in t he N ot -s t r e s se d and S t r e s s f e ma d le
s t u d e n t s
T able A-14: M e a n ( 9 5 % C . I . ) l e v e l s o f N K C A ( % k i l l i o n f g ) m a l e a n d f e m a l e
T able A-15: M e a n ( 9 5 % C . I . ) r -c a et ll in i t ho e s N ot -s o tr ef ss e d and N K C S A t r e t s s fo e ma d le N K
s t u d e n t s
T able A-16: M e a n ( 9 5 % C . I . ) r -c a e t l l i n o m s a l e o a n f d f e m N a K l C e A s t u d t e n o t s N K
T a b l -17: e MA e an ( 95% C.I .) C D 4 a n d C -c D e 8 l l T l l e s v e ( % ) i n the N ot -s t r e s s e a d n d S t r e s s e d
subgroups
- 1 2 - I m p e r i a l C o l l e g e L o n d o n

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
T able A-18: M e a n ( 9 5 % C . I . ) C D -c 4 e ll le a ve n ls d ( %) C D in 8 the T N ot -s tr e ss e d and S t r e s s ma e d le
s t u d e n t s
T able A-19: M e a n ( 9 5 % C . I . ) C D -c 4 e ll le a ve n ls d ( %) C D in 8 the T N ot -s tr e ss e d and S t r e s s f e ma d le
s t ud e n t s
T able A-20: M e an ( 95% C.I .) C D 8 -c T e l l l e v e l s ( % ) o f m a l e a n d f e m a l e s t u d e n t s
T a b l e A-21: M e a n ( 95 % C. I .) P SS l e ve l s i n t h e t h r e e gr o up s at t h e E xa m t i m e p o i nt
T able A-22: M e a n ( 95 % C. I .) P SS s c o r e s i n ma l e s u bj ec t s i n t h e t h r e e gr o up s a t t h e E x a m me t i point
T able A-23: M e a n ( 95 % C. I .) P SS s c o r e s i n f e m a l e s u bj e ct s i n t h e t hr e e gr ou p s a t t h e E x a m t i m e p o i n t
T able A-24: M e an ( 95% C.I .) S t a t e a n x i e t y s c t o h r e m e s a l e i s n u b j e c t s o f t h e S -hypnos e l f is , J oh re i a nd
R e l a x a t i o n c o n t r o l g r o au t p b s a s e l i n and e th e E x a m t i m e p o i nt
T able A-25: M e an ( 95% C.I .) S t a t e s c o r e t s h e f i e n m a l e s u b j e c t s S i e n l f-hyp t h e no s is , J ohr e i a nd
Re la xa t io n c ont rol gr oup at b a s e l i n and e t h e E x a m t i m e p o i nt
T able A-26: M e a n ( 95% C.I .) NKCA le ve ls ( % kil lin g) in t h e t hr e e gr ou p s a t t h e E x a m t i m e p o i n t
T able A-27: M e a n ( 95% C.I .) NKCA le ve ls ( % kil lin g) in ma le s u bj e ct s in t h e t hr e e gr o u ps a t t he Ex a m
t i m e p o i n t
T able A-28: M e a n ( 95% C.I .) NKCA le ve ls ( % kil lin g) in f e ma le su b je ct s in t h e t hr e e gr ou ps a t t he
E x a m t i m e p o i nt
T able A-29: M e an ( 95% C.I .) l e v e l -c s e l l o f ( % ) N K o f m a l e ts he t gr u d oe up n t s s o f t i h n e S e l -hypnos f is ,
J o h r e i a n d C o n t r o at l s b a s e l i n and e t h e Ex a m t i m e p o i n t
T able A-30: M e an ( 95% C.I .) l e v e l -c s e l l o s f ( % t N ) h K e f e i m n a l e s u b j e c t s i n t h e S -hypnos e l f is , J ohr e i
a n d R e l x a t i o n c o n t r o l g r o at u p b s a s e l i n ae nd t h e Ex a m t i m e p o i n t
T able A-31: M e an ( 95% C.I .) l e v e l s o -c f e l l C D 4 ( % ) T o f m a l e t s h t e u S d e l f-hypnosis, n t s i n Johrei and
R e l a x a t i o n c o n t r o l g r o au t p b s a s e l i n and e t h e E x a m t i m e p o i nt
T able A-32: M e an ( 95% C.I .) l e ve l s o f C -c D e 4 l l s T ( % the ) f e i m n a l e s t u d e n t s i n t h e S -hypnosis, e l f
J o h r e i a n d R e l a x a t i o n c o n t r o l g ar t o b u a p s e l i n and e t he E x a m t i m e p o i nt
T able A-33: M e an ( 95% C.I .) l e v e l s o -c f e l l C D 8 ( % ) T o f m a l e t s h t e u S d e l f-hypnosis, n t s i n Johrei and
R e l a x a t i o n trol c o groups n a t b a s e l i n and e t h e E x a m t i m e p o i nt
T able A-34: M e an ( 95% C.I .) l e v e l s o -c f e l l C D s 8 ( % the T ) f e i m n a l e s t u d e n t s i n t h e S -hypnosis, e l f
J o h r e i a n d R e l a x a t i o n c o n t r o l g ar t o b u a p s e l i n and e t he E x a m t i m e p o i nt
T able A-35: Co r r e la t ion be t we e n t he CD4 g r a d i e n t ( c e l per l s l pe r m o n t h ) a n d t st h re e s s pe r ce pt ion
s c o r e s a n d t h e p e r c e i v e d q u -of-l a l i f t e y a t r e c r u i t m e n t t i m e p o i n t ( p r e ) a n d -mont f o u r hs
a f t e r t h e r e c r u i t m e n t ( p o s t )
T able A-36: C o r r e l a t s i b o e n t w e e n t h e C D 4 g r a d i e n t pe ( c e r l l s pe r m o n t h ) a n d t h e c h a n s g c e o r e s of
s t r e s s p e r c e p t i o n s c a l e s
T able A-37: Numbe r of H I V-i n f ec t e d i n d i vi d u a ls who had vi r a l l o a d l e ve l c h e c k a t th e mo nt hly t ime
pe r i o d s f r m o t h e R ec r u i t me n t to four mont hs a f te r t he r ec ru it me nt (Te r m 4)
P h . D . a t U n i v e r s i t y o f L o n d o n
- 1 3 - I m p e r i a l C o l l e g e L o n d o n

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
T able A-38: Co r r e la t ion be t we e n t he vi r a l l o a d l e ve l gr a d i e n ts (log-t r a nsf o r med vir a l c o p ies p er l p e r
m o n t h ) a n d t h s e t r e s s p e r c a e n p d t i t o h n e p e r c e i v e d q u -of-l a l i t f e y s c o r e at s re c ru it me nt t ime
p o i n t ( p r e ) a n d f o u r m o n t h s l a t e r ( p o s t )
T able A-39: Cor re la t ion be t we e n t he vi r a l l o a d l e ve l g r a d i e n t log-t ( r a nsf or me d copie s pe r l pe r mon t h)
a n d t h e a n c g h e s c o r e s o f p e r c e i v e d s t r e s s a -of-l n d i q f u e a l s c i o t r e y s
T able A-40: Cor re la t ion be t we e n t he N K g r a d i e n t ( c e pe l l r s l pe r m o n t h ) a n d t st h re es s pe rc e pt ion
s c o r e s a n d t h e p e r c e i v e d q u -of-l a l i f t e y a t r e c r u i t m e n t t i m e p o i n t ( p r e ) a n d -mont f o u r hs
a f t e r t r h e c r u i t m e n t ( p o s t )
T able A-41: Cor re la t ion be t we e n t he N K g r a d i e n t ( c e pe l l r s l pe r m o n t h ) a n d t h e c h a n g e s c o r e s o f
p e r c e i v e d s t r e q s u s a l a i n -of-l t d y i f e s c o r e s
Table A-42: M e an ( 95% C.I .) le ve ls of t he St at e a nx iet y a n d P S s S c o r e s -individ i n ua t ls h in e the H I V
S e l f-h y p n o s i s , J o h r e wa i i t-l a n i d s t co e d nt r o l gr o u p s at t h e B as e l i n e an d t h e P o s t-
i n t e r v e n t i o n t i m e p o i n t s
T able A-43: M e an ( 95% C.I .) le ve ls of t he L o C , M C S a n d P S Q in I the HIV-i n d i v i d u a l s i n t h e S -e
l f
h yp n o s i s , J oh r e i an d wa i t-l i s t e d c o n t r o l g r o au t p t s h e B a s e l i and n e P o st -in t er ve nt ion t ime
points
T able A-44: M e an ( 95% C.I .) le ve ls of r e g r e s s i o n g r a d i v e i n r t a s l i l n o a d l e v -t e rl a nsf s or ( me L o g d ) i n
H I V-i n f e c t e d i n d i v i d u a l s i n t h e S -hypnosis, e l f J o hr e i a nd wa i t -l i s t e d c o n t r o l g r o u p s
T able A-45: M e a n ( 5% 9 C.I .) le ve ls of r e gr e ss ion gr a die nts in N K -c e l l (counts pe r l p e r m o n ) t i h n
H I V-i n f e c t e d i n d i v i d u a l s i n t h e S -hypnosis, e l f J ohr e i a nd wa i t -l i s t e d c o n t r o l g r o u p s
Text box 1: Pr o j e c t s y n o p s i s
P h . D . a t U n i v e r s i t y o f L o n d o n
Li s t of T e x t b o x es
Text box 2: Ap p r a i s a l o f a r s t r e s s o
38
Text box 3: El e m e n t s o f c o p i n g wi t h a t h r e at 38
Text box 4: Ps yc ho l o gi c a l i n t e r ve n t i o n s i n t h i s p r oj ec t 43
Text box 5: Su m m a r y o f h y p o t h e s e R s e : S t r e -re s s la te d cha nge s of e ndoc r ine s ys te m wh ic h ma y
c o n t r i b u t e t o s u p p r e s s c e l l u l a r i m d m e r u n s e u s t r a e i n s e p d o n s t e r s e s s u n
- 1 4 - I m p e r i a l C o l l e g e L o n d o n
21
48

P s yc h o l o g i c a l i n t e r v e n t p i s o y n c h -n o a e n u d r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
A C T H : a d r e n o c o r t i c o t r o p h i c h o r m o n e
A N O V A : a n a l y s i s o f v a r i a n c e
A P -1: a c t iva t io n pr ot e in 1
ART : a n t i -r e t r o vi r a l t r e at m e nt
C B G : c o r t i s o l b i n d i n g g l o b u l i n
C D : c l u s t e r s o f d i f f e r e n t i a t i o n
C F S E : c a r b o x y f l u o r e s c e i n m i d s y u l c c e s i t n e r
c p m : c o u n t p e r m i n u t e
C R F : c o r t i c o t r o p h i n r e l e a s i n g f a c t o r / ( h o r m o n e )
C R P : -r e C a c t i v e p r o t e i n
C S F : C o l o n y s t i m u l a t i n g f a c t o r
C T L : ( c y t o t o x i c / c y t o l i t i c T l y m p h o c y t e )
C V : c o e f f i c i e n t o f v a r i a t i o n
D H E A (-S ) : d e h y d r o e p i a n d r o s t e r o n e ( s u l p h a t e )
A b b r e v i a t i o n s
EE G : e l e c t r o e n c e p h a l o Q o g L : r q a u a m l i t y o f l i f e
E : T r a t i o : E f f e c t o r v s . T a r g e t r a t i R o C T : r a n d o m i c s o e nt d r o l l e d t r i a l
F I T C : f l u o r e s c e i n i s o t h i o c y a n a t e
F C S : f o e t a l c a l f s e r S A u M : m s y m p a t h e t i c -m a e d r u e l n l o a
G A B A : g a m m a a m i n o b u t y r i c a c i d
G C R : g l u c o c o r t i c o i d r e c e p t o r
H I V : h u m a n i m m u n o d e f i c i e n c y v i r u s
H P A : h y p o t h a l a m u s p i t u i t a r y a d r e n a l ( a x i s )
H S V : h e r p e s s i m p l e x v i r u s
I E S : I m p a c t o f E v e n t S c a l e
I L : I n t e r l e u k i n
I F N : i n t e r f e r o n
I T A M / : i m I m u T n o I r e c M e p t o r t y r o -bas s i n ee d
a c t i v a t / i o n h i b i t o m r o y t i f s
K I R : k i l l e r i m m u n o g l o b u l i n l i k e r e c e p t o r
KP SS: K e s s e l e r P er c e i ve d So c i a l Su p p o r t
Lo C : Lo c u s o f C on trol
L P S : l i p o p o l y s a c c h a r i d e
M C R : m i n e r a l c o r t i c o i d r e c e p t o r
M H C : m a j o r h i s t o c o m p a t i b l i t y c o m p l e x
NCR: n a t u ra l c yt otoxic re c ept or s
N F B: n u c l e a r f a c t o r k a p p a B
N K c e l l : N a t u r a l K i l l e r c e l l
N K C C : N a t u r a l k i l l e r c y t o t o x i c a c t i v i t y
P B L : p e r i p h e r a l b l o o d l y m p h o c y t e
P B M C s : p e r i p h e r a l b l o o d m o n o n u c l e a r c e l l s
P B S : p h o s p h a t e b u f f e r s a l i n e
P E I : P e r s o n a l i s e d E m o t i o n a l I n d e x
P F A : p a r a f o r m a l d e h y d e
P H A : p h y t o h a e m a g g l u t i n i n A
PI: propidium iodide
P N I : p s y -n c h e o u r o-immunology
P P D : p u r i f i e d p r o t e i n d e r i v a t i v e
P S S : P e r c e i v e d S t r e s s S c a l e
P S Q : P e r s o n a l i t y S y n d r o m e Q u e s t i o n n a i r e
P S Q I : P i t t s b u r g h S l e e p Q u a l i t y I n v e n t o r y
R E M : r a p i d e ye m o ve m e n t
S A S : S t a t i s t i c a l A n a l y s i s S o f t w a r e
S D : s t a n d a r d d e v i a t i o n
S E B : S t a p h y l o c o c c a l E n t e r o t o x i n
SI BS: S p i r i t u a l I n v o l v e m e n t a n d B e l i e f s S c a l e
SoC : s e n s e o f c o h e r e n c e
S O P s : s t a n d a r d o t p i e n r g a p r o c e d u r e s
S P S S : S t a t i s t i c a l P a c k a g e f o r S o c i a l S c i e n c e s
S T A I : S t a t e a n d T r a i t A n x i e t y I n v e n t o r y
T C I : T e m p e r a m e n t a n d C h a r a c t e r I n v e n t o r y
T C M : t i s s u e c u l t u r e m e d i u m
T h . : H e l p e r T l y m p h o c y t e
T N F : T u m o u r n s e i c s r f a o c t o r
T-r e g : r e g u l a t o r y h e l p e r c y t T e l y m p h o
T U N E L : T -m d T e d i a t e d d U T P n i c k e n d l a b e l l i n g
W H O : W o r l d H e a l t h O r g a n i s a t i o n
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 5 - I m p e r i a l C o l l e g e L o n d o n

P s yc h o l o g i c a l i n t e r v e n t p i s o y n c h -n o a e n u d r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
A c k n o w l e d g e m e n t s
I wis h t o t ha n k a ll t he pa rt ic ipa nt s wh o t oo k p a r ts in th e pr oj e ct as st u d y s u bj ec ts .
T he wor k in t his t he s is wa s funded by t he Jo hr e i A c a d e m y and J oh r e i As s o c i a t i . o n m I os t gr a at m ef ul t o
t he m f or t he ir g e n e r o s i and t y f o r t h e i r k i n d support i n d e v e l o p i n g m a t e r i a l s o t f h Je ohr e i in te r ve nt ion.
I would li ke t o give s pe c ia l thanks to D r . D o n C . H e n f d o e r r h s i o s n e n d u ra b l e c los e s upe r vis io n a nd Pr of .
John H. Gruze lie r f or a llowing me t o s t ar t a nd c o n du ct t he pr o je ct . T he y h a ve gi ve n me ins pir at io n to s ee
the pr oj e ct through. D r . T a n n i s M . L a i d l a w , D r . P r a b u d h a D w i v e d i a n d e M d r . B r y a n B e n n e t t w
t o g e t h e r w i t h m e a s a r e s e a r c h t e i a m n f v st o i r udie v o t h s. e I a m v er y gr a t e ful t o t he m. One of th e
ps yc holo gic a l int e r ve nt ions , the Se l f-h y p n o s i s t r -up a i s en s si io ns n , g wa s pla a nned n d a nd f o l l o w
c onduc te d by Dr . La idla w. T h e m o c k n e u -f r e o e d b a c k s e s s i o n s ( r e l a x a t i o n c o n t r o l we ) r e c on du ct e d by Dr .
D w i ve d i . M r . B e n n et t wa s in charge of pa t i e n t r e c r u i t m e n t a n d o r e g d a n m i e s e t i n g s f o r the pa rt ic ip a nts .
Without any of the m, t h i s p r o j e c t w o u l d u n d o u b t e d l y h a v e n e v , e r o r b e v n e n c o s m . t p I a l ar m e t e d
mos t in deb te d to t h e i r gr ea t c o n t r i b u t s, i pe o n rs on a l he lp a nd wa r m supp or t .
My s p e c i l a tha nks a ls o go to P r o f . A d r i a n P . B u r g e s s a n d D r . M a r t i n R . G o . o Th d i e y r g a v e m ve e r y
us e ful a n d e n c our a ging input s a t t h e tr a n sf er e x a m to P h . D. f ro m M .P h il. Dr . Ala n W. St e el contributed t o
the i n v i vo H I V-s t u d y a s a n i n d e p e n d e n t r e s e a l r e c h t e r c a t s o e m controls. a t c h e d D r . S i m o n E . B a r t o n
k i n d l p y e r m it t e and d ga ve support t o r e -pa c t ie r nt u s in i his t c linic H I . MV r . M oha me d Sh amj i he lp e d me
t o st ar t t he i n v i et xpe r o r ime nt s be fore t he pr oj e ct co mme nc ed . I a m in de bt e d t o t he ir kin d he lp a nd w a r m
s uppor t . I a p p r e c i a t M e .Sc . st u d e n t r e s e a r c h e rs, I j e o m U a g w u-Onuoha a n d A l e x G , a al nd e B. Sc . s t udent r e s e a r c h e r s, L i n d a F a r a h a n i , C a t r i n a L y n c h , r N i s c t k i E n n e z o B r , i n C c h a t , T and o m He F le r ne a n c h
M a r c o ne l l , f or t he ir c ont r ibut ion t o t he s tu dies . I a p r ep c iat e t he s e cr et ar ia l a s s ist anc e give n by M r s . Ann
E b b e r s o n t h r o u g h o u t m y P h . D . . T c o h u a n r k s e a l s go o t o a ll t he r es e ar c h st a ff / c lin ic a l la bo r at or y st af f /
s t u d e n t s a t C h a r i n g C r o s s N e u r o s c i e n c e D i v i s i o n , a t C h e l s e a a n d W e s t m i n s t e r nt I m m u n o l o g y D e p a r
a n d S t . S t e p h e n ’ s A I D s T r u s t K o b w l h e r o C k e n p t r e m e g o i n g w h e n I w a . s s t r u g g l i n g
I n a d d i t i o n m , ve I r y a gr a t ef ul t o P r o f . M a r k J , e Pn rof s e . n Y u k i h i s a K u r a s a w a, D r . ieson, G r a Dr h . a m J a m
G e r a l d S , t Pr e i of n . Fr a nc es Got c h, Dr . N a t h a l i Fouquet, e Dr . Philippe Dona t ie n , Dr . Da vid V e r n o n, Dr.
M a l c o l m H a w , k e n P r o f . T o m and S e n s k P y r o f . J u f o l r t he i r a c o m m B en u t s c o n k t he i m n a n g u sc h r i a pt. m I
would l ike t o thank my e xa mine rs , P r o f . P h i l E v a n s ’d a n P d r o R f e . v Goulding, N i c k f or t heir t houghtf ul
a n d u s e f u l e s tu ions g g . To t he a f o r e m e n t i o n a e n d m a n y o t h e r u n n a m e d c o l l e a g a u n e d s f r i e n , d who s
ha ve a ls o h e lpe d t owa r ds t he c o mp let io n o f t his t h es is , I e xt e n d my s in c er e t ha n ks .
A k i r A a I T O N
London, August, 2006
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 6 - I m p e r i a l C o l l e g e L o n d o n

Chapter I
Introduction
- 1 7 -

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
CO NTENTS O F CH APTER 1
1 . 1 P r o j e c t o v e r v i e w
1 . 2 T h e o r e t i c a l f r a m e w o r k
1 .2 .1 I m m u n e s y s t e m
I n t r o d u c t i o n
1 . 2 . 1 . 1 I n n a t e a n d a d a p t i v e i m m u n i t y
1 .2 .1 .2 C o m m u n i c a t i o n b e t w i e m e m n u n e c e l l s
1 .2 .2 N e u r o-e n d o c r i n -i o m m u n e i n t e r a c t i o n
1 .2 .2. 1 B r a i -t n o-i m m u n e p at h w a y 30
1 .2 .2. 2 I m m u n e-to-b r a i n p a t h w a y
1 .2 .2 . 3 C i r c a d i a n n t h e r -e n h e n u d y r o c o t r i h n -i o m m u n e n e t w o r k
1 .2 .2 . 4 C i r c a d i a n r h y t h m a n ud b jecti s ve w e l l -b e i n g 35
1 .2 .3 P s y c h o l o g i c a l i n p u t i n -n t e h u e r o-e p s n d y o c c h r o i n -i o m m u n e n e t w o r k
1 .2 .3. 1 Str e s s o r 36
1 .2 .3. 2 St r e s s p e r c e p t i o n
1 .2 .3 . 3 P s y ch o l o g i c a l t r a i n i n g i n t e r v e n t i o n
1 .2 .4 St r e s s-a s s o c i a t e d c h a n g e s
1 . 2 . 4 . 1 C h r o n o l o g i c a l d e f i o n f i s t i r e o s n s r e s p o n s e
1 .2 .4 . 2 A c u t e s t r e s s r e s p o t n h s e s n e -e i u r n d o c r i n -i o m m u n e n e t w o r k 44
1 .2 .4 . 3 Su s tai n ed s tres s and ch an ges in th e p s y c h o-n e u r o-e n d o c r i n - o
1 . 3 A p p r o a c h t a k e n
i m m u n e n e t w o r k
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 8 - I m p e r i a l o C n o d l o n l e g e L
22
27
32
33
37
39
43
46
19
22
30
36
43
49

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
1.1 Th e p r o j e c t o v e r v i e w
S t r e s s i s i n e v i in t a e b v l e r y d a y l i a n f d e it a f f e c t s m e n t a l a n d p h ys i c a l w e l l-b ein g b oth
b e n e f i c i a l l y a n d d e t r i m e n t a l ly [ C o h e n & H e r b e r t , 1 9 9 6 ; E v a n s e t a l . , 2 0 0 0 ; M a r m o t , . 2 Th 0 0 is 4 ]
p roject i s b as ed on t h e h yp oth es is th at th e d etrimen tal ef fect s o f s t res s u p o n p s yc h o l o g i c a l w e l l-
b e i n g a n d g e n e r a l h e a l t h iate c a n d b y e p sa ych l l ol e ogi v c al i n t e r v e n t [T i e o x n t b o x ]. 1
P s y c h o l o g i c a l i n t e r v e n t i o n i n t h e -s c o om n t ati e x c t m ed o f ici np e s [ y Wal c h o d s tein e t al.,
2 0 0 1 ; W a l k e r e t a l . , 1 9 9 h 9 a ] s b o t h r a i n i n g a n d p r a c t i c e a s , p b e c t o s t h o f to p ro w vi h d e i c h a i m
o t h e r p e r s p e c t i v e s o f l i f e e v e n t s ( p s e t r e c s e s p t ) i an o d n cop in g s ki ll s (s tres s man ag emen t) in
o r d e r t o r e d u c e le t vels h e o f s tres s . T w o p s y c h o l o g i c a l i tions n t e r u s v e d n i n is t p roject h we re
Self-h yp n os is an d J oh rei , a J ap an es e s ys t em e n c o m p a s s i g n s tres s man age men t . Th es e
i n t e r v e d n to t e n c i o u o r a g n e s t h e p a r i t i c m i p a n t s t o s e c u r e t h e i r o w n t i m e f o r with t h e m s e l v e s
r e l a x a t i o n t e c h n i q u as e s well as to r e d u c e s t s r s e b y p r o v i d i n g a l t e r n a t i v e p e r s p e c t i v e , s o a f n d
c o p i n g s t r a t e g i fo e s r, s t r e s sf u l l i f e e v e . n t s
Th e f i e l d s o f p ‘ s y c h o-n e u r o-e n d o c r i n o l o g ’ y [ d e K l o e t , 2 0 0 0 ; S a p o l s k y e t a l . , 2 an 0 0 d 0 ]
‘p s y c h o-n e u r o-i m m u n o l o g ’ y [ A d e r & C o h e n , 1 9 9 3 ] a r e b as ed on th e con cep t of Descartes'
‘m i n d a nd b o d y ’ or ‘t h e w a y w ith th e b o d y -m i n d’ [ Y u a s a & K a s u l i s , 1 9 8 . 7 A ] g ro wi n g b od y of
evid en ce s u gges t s t h at t h ere are cros s reg u lator y in flu en ces b etween ps ych ol ogic al, n eu rological ,
en d ocri n ol ogi c al an d i mmu n ol ogical s ys t ems . Th is h as led in ves tigat ors t o p rop os e th e
e x i s t e n c e o f a n i g n r t a e t e d p s y -n c e h o u r o-e n d o c r i n -i o m m u n e n et work , in wh ich a ch an ge in on e
facet h as con s eq u en t i al i n fl u en ces up on oth er p arts of th e n etw or k. Th e p rimar y m ed iators in th e
n e t w o r k i n c l u d e c a t e c h o l s a m f i r n o e m t h e s y m p a t -a h d e t r i e c n o-m e d u l l a ( S AM ) s ys t e m , a d r e n a l
h o r m o n e s f r o m t h e h y p o t h a l a -pituitary-ad m u s ren al ( HP A) a xi s an d a m yriad of c o mp on en ts of
t h e i m m u n e s y s t e m , i n c l u d i n g i n d i v i d , u cell a l c se ul rface l s recep to rs , an d in tracell u lar an d
in tercel l u l ar mes s en gers (c yt okin es ) .
Th e fiel d of s t res s res ea rch h as n ot yet ag reed u p on a definition o f s tr es s th at i s u s ed in all
s t u d i e s . Fo r e x a m p l e , th e d i s t i n c t i o n b e t w e e n a c u t e a n d s u s t a i n e d s t r e s s i s a m b i g u o u s a ies n d v a r
f r o m s t u d y t o s t e u d c y u . r r e I n n t t h h e , s acu i s te or s u s tai n ed s tres s was d is tin gu is h ed on th e
ba s is of t i m e i n a b i o l o g i c a l c y c l s t e . r e s A s c s u w t d a e f i n e d a s w h e n e f f e c t o f s t or r e s tres s
r e s p o n s e i s c o n t a i n e d w i t h , i n i . o e n e a d a y s i n g l . e In c on c tras i t , r s u c s t a i n d e d i s t a r e n s s r h y t h
was d efi n ed as s tres s th at th e effect l a s t s f o r m o r e t e h a d n a . y T o n h i s lead s to a wo r ki n g
h yp oth es is th at s u s tai n ed s tres s is as s ociated with altere d c i r c a d i a n p a t t e r n s p o s f y c h t o-
h e
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 9 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
n e u r o-e n d o c r i n -i o m m u n e n et wor k. Si n ce th e p s ych ol ogical in terven tion s u s ed in the p roject
r e q u i r e w k e s e o f t r a i n i n g a n d i p r s a i c n t v i e s c e t , i g a t f t h o i c u o se n d o n t h se u s tain ed st res s .
P r e v i o u s r e s e a r c h h a s s h o w n t h a t th e s t r e s -as s s oci at ed i n a p p r o p r i a t e r e s p o n s e o th f e
immu n e s ys tem h as b een s h own to c o m p r i s : e
1 . Im p a i r e d c e l l u l a r i m m u n e r e s p , o n w s e h s i c h a l d e t o a n i n c r e a s e i n s u s c e p t i b i l it y t o
in fection an d mal i gn an c y [ G a r s s e n , 2 0 0 4 ]; a n d
2 . Ex c e s s i v e i n f l a m m a t o r y r e a c t , i w o n h s i c h m a y b e d u e t o i m p a i r e d s u p p r e s s i v e -s
e l f
r e g u l a t , i o r n o v e r-p r o d u c t i o n o f -i n p f r l o a m m a t o r y c y t o k i n de in s g l to e a an
au gmen t ed s everi t y of s ymp to ms o f aller g y or au toim mu n e d is eas es [ C l e a r e , 2 0 0 3 ].
T h i s p r o j e c t f o n c u t h s e d f i r s t p t a - r th e s t r e s s-i n d u c ed i m p e n a t i o f r m c e l l u l a r . i m m u n i t y
T h e e f f e c t s o f s t r e s s a n d p s yc h o l o g i c a l i n t e r v e n t i o n u p o n th e p s y c h -n o e u r o-e n d o c r i -n
o
i m m u n e n et wor k we re in ves tig ated i n v i in v o u n ivers it y s tu d en ts faci n g ex ams as a n examp le of
individ u al s wi th time-limited s u s t a i n e d s t r , e s s a n d -in i fected n a H d I u l t V s as an exa mp le of
i n d i v i d u a l s o w n i g o t i h n , g life-lo n g , d i s e a s -a e s s o c i a t e d s t r e s s . Ge n e r a l a n d m e n t a l w e l l-b ein g
w e r e i n v e s t i g a t e d t h r o u g h q u e s t i o n n a i r e s d e s i g n e d t o m e a s u r e p e r c e iv e d s tres s , an x iet y, q u a l -i
t y
o f -li fe, an d s leep q u al it y. Th e e ffects of s t res s u p on th e p s y c h o-n e u r o-e n d o c r i n -i o m m u n e
n etwork were exa mi n ed t h rou gh im mu n e p rofiles in clu d i n g d i s eas e p arameters . As s ociation s
b e t w e e n t h e m e d i a t o r s p o s f y c t h o-n e e u r o-e n d o c r i n -immu o n e n et work were al s o i n v e s t i g a t ed
i n v i in t r ord o er t o d em o n s t r a t e a n y d i r e c t s bl etween i n k h orm on e level s an d immu n e
p aramet ers .
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 0 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
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P h . D . a t U n i v e r s i t y o f L o n d o n - 2 1 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
1.2 T h e o r e t i c a l f r a m e w o r k
1 . 2 . 1 I m m u n e s y s t e m
H u m a n s a r e c o n s t a n t l y p r o s n (vi e ru s es t , b act o eri a, i n f e c t i o
f u n g i , a n d m u l t i-c e l l u l a r p a r a s i ) t a e n s d t o m a l i g n a n c y t h r o u g h m u t a t i o n s f r o s e m l f ’. ‘ It is th e
f u n c t i o n a l r e s p o n s i b i l i t y o f t h e i m m u n e s y -s s el t f e an m d a t l o t e r e -s e c elf d o g an n i d s te o n o n
p r o d u c e a n a p p r o p r i a t e i m m u n e r r e m e s o v p e o n i t s i e n o t r o d e r to m a i n t th a i e n gen e ral h eal th of
t h e b y. o d An y i m m u n e r e s p o n s e i n v o l v e s , f i r s t, r e c o g n i t i o n o f t h e p a t h o g e , n an o d r m u t a t i o n
th en s e c o n d, a r e a c t i o n t o e l i m i n a te it.
1 . 2 . 1 . I 1 n n a t e a n d a d a p t i v e i m m u n i t y
T h e i m m u n e s y s t e m h a s b e e n c l a s s c i o f m i p e o d n e n i t s n : t ( o 1 ) i t n w n o a t e ( i n b o -r
n : n o n
s p e c i f i c ) i m m u n i ; an t y d ( 2 ) a d a p t i v e ( a c q u i r e d : -s p a p t e h o c g e n i uf n it i y [T c a b ) l e ]. i 1 m m
I n n a t e i m m u n i t y
I n n a t e i m m u n i s t y -s n o pn ecifi c an d is d e f i n e d a s -b t h orn e di efen n ce mech an is m o f th e
b o d y . T h e i n n a t e i s p n r e a s e t n t u r a t a i s b l r i e s r p t o n h i s ib a m ln e m d for u tn h e e earl y s / y s t e m
i m m e d i a t e d e f e n c e a g a i n s t a n i d n f m e a c l t i g o n . n a Alth n c y ou gh th is fo rm of i m mu n it y h as n o
m e m o r y o f -s n o e n l f , t h e s e c e l l s a r e a b l e -s elf t o rgan r e c is o ms g n i (t s u mou e n r o n c el ls or
i n f e c t e d c e l l s ) b y m ‘ i s s i n g s e l f’-s i g n a l [ M o r e t t a e t a l . , 2 0 0 , 2 ] a n d d e f e n d t h , e e v b e o n d y w h e n
the t r i g g e r i s n o t s u f f i c i e n t t o a c t i v a t e t h e a d a p t i v e i m m u n e s y s t e m . T h e r e a to r e t w o e l e m e n t s
i n n a t e i m m , u i.e. n i t h y u m o r a l a n d c e l l-m e d i a t e d i m m u : n i t y
1 . H u m o r a l i m m u n : i the t y s e c r e te d m o l e c u l e , s wh ich in cl ud e comp lemen t , l ys oz o me,
f i b r o n e c t i n , a c u t e p h a s e p r o t e ( i n e s -r . e g a . c t e d C p r o (C t R e i P ) n ), ei cos an oi d s , n at u r al
a n t i b o d i e s a n d p -in r o fla mmat or y c yt o ki n es (e. g. I n t e r l e u s k ( i I L n s ), I n t e r f e r o n s ( I s), N F
c o l o n y s t i m u l a t i n g f a c t ( o r C s S s) F an d t u m o u r n e c r o s i s f a c s t o ( r T N Fs)) .
2 . Cellu la r im mu ni ty : t h e p r i n c i p a l c e l al re p h agoc t y yt es p e s i n i
(e.g . ma cr op h ages , m on oc yt es an d gran u loc ytes in clu d in g n eu trop h ils ) an d n atu ral
killer (N K) cel l s .
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 2 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Ad a p t i v e i m m u n i t y
A d a p t i v e i m m u , n i o n t y t h t e h e o r h a , n d i s t h e d th e at f rec e ogn n ic s es e a n d m e c h a n i s m
figh ts agai n s t s p eci fi c in fect i ou s or gan is ms an d d e v e l o p s m e m o f r y s p e c i f i c a n t i g o e f n s s u c h
p a t h o g e n s. T h i s a l l o w s a l l s u b s e q u e n t r e s p o fecti n s e on s t o o p r oceed t h e mor s a m e e rap i id n l y
an d effect ivel y. T h i s a d a p t i v e i m m a u l n s i o t h s y a h u m o r a l a n d c e l lu l a r c om p o n e n t s .
1 . H u m o r a l i m m u n i t s y m e d i a t e d b y a v a s t a m o u -s n t p ecifi o f c an p a ti t b od h o ig es e n
p r o d u c e -l d ymp b h oc y yt es B . An ti b od ies p r o v i d e p r o t e c tion f r o m ath p ogen s b y
n eu trali s i n g t oxi c c omp on en ts o f p ath oge n s , b y c oatin g p ath o gen s an d th ereb y
t a r g e t i f n g o r d i s p o s p a h l a g o b c y yt e s ( t h i s i s k n o w n a s o p s o n isation), an d b y acti vat in g
c o m p l e m e n t t o t r i g g e r e l s y s a n d i n g e s t i o n o f p a t h o g e b n y s p h a g o c y t e . s Sp ecifi c
m o l e c u l e s p r o d u c e d b y i m m u lls n e (n c ae mel y, Th .1 an d Th .2 cy t o k i n e s) [s ee als o
T a b l e ] als 1 o p la y a maj o r r ol e in re gu lati on of th e ad ap tive im mu n e s ys te m as me d ia
o f c e l l-c e l l c o m m u n i c . a t i o n
2 . Cellular immunity i s b a s e d o n t h e a c t i v i t i e s m o p f h o t c w y o t e - y s p e a , s n -d
o T f B l y
l y m p h o c y t s. e Each l ymp h oc yt e can s p eci ficall y reco gn is e an d react with on e of th e
th ou s an ds of f orei gn p rot ei n s , i.e . an tigen ic ep itop es fou n d on / in p ath ogen s .
T h e -l ym B p h o c yt e s a r e r e s p o n s i b l e f o r t h e p r o d u c t i o n o f s p e c i f i c a n t i b o d ie s , an d
h ave B-c e l l a n t i g e n r e c e p t o r ( B C . R ) T h e B C R i s a m e m -b b r ou a n ne d for m of th e
a n t i b o d y -ly t m h p h a o c t y t e w t i l h l e s e c r e B t e a f t e r f o l l o w a i c n t i g v a ti o n b y s p eci fi c
an tigen a n d d i f f e r tiation e n int o p las ma ce ll s .
T h e -l T y m p h o c y t e s h a v e b e e n s u b d i t v o i d t e w d o -p i s n op u b u lat ion s acc ord in g to t h e i r f u n s, c t i.e. i o t n h e c y t o -l t y o m x p i h c o c T y t e ( C T L ) a n -l d ymp t h oc h yt e h e l p e r T
( T h . ). Both s u b s e t s e x p r e s s T-c e l l a n t i g e n r e c e p t s o r ( T C R ). Th e TC R is s p eci al l y
a d a p t e d t o d e t e c t a n t i g e n s d e r i v e d f r o m f o r e i g n a n p d r po at t e hi ogen n s s .
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 3 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
I N N A T E
A D A P T I V E
T a b l e 1: C l a s s i f i c of a t he i o ma n in c ompone nt s o f the i m m u n e s y s t e m
H U M O R A L C E L L U L A R
C y t o k i n e s -i ( n P f l r a m o m a t o r y )
A c u t e p h a s e p r o t e i n s
C o mp le me nt
L y s o z o m e
N a t u r a l a n t i b o d i e s
C y t o k i n e s
A n t i b o d i e s
( I m m u n o g l o b u l i n )
Na t u r a l K i l l e r ( N K ) c e l l s
T h . 1
( c e l l u l a r )
T h . 2
( h u m o r a l )
IgM
IgG
I gA
IgE
Nat u ra l K i lle r ( NK ) cell s
P h a g o c y t e s
T-l y m p h o c y t e s
M a c r o p h a g e s
M o n o c y t e s
Gr anu lo c yt e s
C yt o t o x ic T-c e lls ( C T L )
He lp er T-c e lls
B-l y m p h o c y t e s ( a n d P l a s m a c e l l s )
C yt ot o xic N K -c e l ls
R e g u l a t r y o N K -c e l ls
N e u t r o p h i l s
E o s i n o p h i l s
B a s o p h i l s
T y p e I ( T h . 1 )
T y p e I I ( T h . 2 )
Reg u lat o r y ( T-re g )
Th e Nat u ral Ki l l e r ( N K ) c e l on l s e of a r t he e p ri n ci p al cel l t yp es in th e in n ate cellu lar
i m m u n e . T s h e y a s r e t l a r e g e m g r a n u l a r l y m p h o c y [ t F e i s g u r e 1 ], wh ich d evel op fr om c o mm on
l y m p h o i d p r o g e n i t o r c e l l s . T h e y m -1 a 5 k % e of u tp h e a mb on o u on t u cl 5 ear cel l fra ction in
n ormal p eri p h eral b l o od .
Fi gur e 1 : A t yp i c a l N a t u r a l K i l l e r c e l l
[T a k e n fr o m Wa s a t c h H e a lt h G r o u p : ht t p : / / w ww . w a s a t c h he a lt h . c o m / -c P e a l l. g ht ml] e s / N K
Th ere are two s u b s et s of N K -c e l l s [ C o o p e r , F e h n i g e r & C a l i g i u r i , 2 0 , 0 1 ] i . 0-2 e 1 0 % of
re g u l a t o r y N -c K e l l s u b s e t (c yt o ki n e p rod u cin g s u b s et [ C o o p e r , F i e g h e r n , T u r n e r e t a l . , 2 0 ) 0 1 ]
a n d 8 0-9 0 % of cyt ot o xi c N K -cell s u b s et [ J a c o b s e t a l . , 2 0 0 , 1 ] w h i c h h a two s p os s ib le ki ll in g
m e c h a n i s m s :
1 . Cytolitic g r a n u l e s ma ke a h ol e in th e me mb ran e of t a r g e t c e l ls c au s in g n e c r o s i s; a n d
2 . Gr a n u l e s o r a c e l l-c e l l c o n t a c t ( e.g . Fas - F a s-l i g a n c d o n t a c t) t ri g gers a cas cad e f or
‘p r o g r a m m e d c e l l ’ d (kn e a own t h as ap op tos is ) [ O p f e r m a n & K o r s m e y e r , 2 0 0 3 in ] th e
t a r g e t c e l l.
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 4 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Th e c y t o l i t i c g r a n u l e e p a m t p h l w a o y y e d b y -cells c is y th t e s o ame t killing o x i c N K
mech an i s m as t h at a p p l i ed b y c ytot oxic T-c e l l s (C T L) . C ytot oxic gr an u les , wh ich con tain
P erfori n an d Gr an z yme A / B, are releas e d on to th e s u rface of th e b ou n d t a r g e t c e l l, an d th e
P e r f o r i n m a k e s a h o l e t o d e s t r o y t h e c e l l m e m b r a n e a n d G r a n z y a m p o e p t i o n s d i u s. c Th e s is s e c r e t i o n o f g r a n u l e s w i t h c o r n g t e a t c t c e t l o l s t a t a k e w s s a e c o f n e d s a n d i s k n o w n a s t h kis e ‘ s o f
d e a t h’ [ T r a m b a s & G r i f f i t h s , 2 0 0 . 3 A ] p o p t o s i s i s e s s e n t i a l in t h e c e l l c to y c m l a e i n t a i n cel lu lar h omeos tas is [ O p f e r m a n & K o r s m e y e r , 2 0 0 3 . ] Th e F a s -r e c e p t o r [ H i n g o r a n i e t a l . , 2 0 0 w 0 ] a s
sh o w n t o t r i g g e r a n -cellu i n t lar r a cas cad e i n d u c i n ap g op tos is wh en th e F a s -l i gan d f rom oth er
cells con tact s [ A l e n z i & W a r r e n s , 2 0 0 . 3 ]
T a r g e t re c o g n i t -cells i o n b y N K
Th e mai n r ol e of N K -c e l l s i s t o r e c o g n i s e a n d k i l l v i r a l i l n y f e ct e d-cel ls a n d t u m o u r-c ells
b oth of wh i ch h ave es cap ed re co gn ition a n d d eath b y oth er i mmu n e c o m p o n e n t s. T h e ex a ct
m e c h a n i s m o f t h e r e c o g n i t i b o n y -c e l N l K s i s u n c l e a r , b r u e t h a t s h e b e e n a h y p o t h e s i t s h a - t N K
c e l l s dc etect a n ‘m i s s i n g s e l f’ [ M o r e t t a e t a l . , 2 0 0 . 2 In ] oth er w ord s , N K -c e l l s l a c k a n t i g e n
s p e c i f i c i t y b u t a r e a b l e t o i d e n t n i f o y n -s ‘ e l f ’. Al l h u man cel ls e xp res s th e maj or
h i s t o c o m p a t i b l i l i t y c o m p l e x ( M H c C l a ) s s I m o l e c u l e s o n t h e c e l l-s u r f a c e. Th e le ve ls of
exp res s ion of th is M HC d e c r e a s e w h e n c e l l s a r e i e n c f t e d o r t u r n i n t o t u m o this u r c e l l s , a n d
d ecreas e of th e M HC cl as s I m olecu le is c a l l e t d h e ‘m i s s i n g s e l f’ [ M o r e t t a e t a l . , 2 0 0 . 2 ]
R ecogn i t i on of t a r g e t c e l ls b y N K -c e l l s is ach ieved b y c omb in ation o f tw o cate go ri es of
r e c e p t o r s, i . . activat e in g an d in h ib it or y re cep tor g rou p s [ M i d d l e t o n e t a l . , 2 0 . 0 Recogn 2 ] it ion of
‘m i s s i -s n e g l f ’ m e a s n t h a t b a l a n c e b e t w e e n a c t i v a t i itor n g y a s in gn d al i s n wei h i gh b s toward activati on d u e to a l a c k o f t h e M H C c l a s s I . R e c o g n i t i o n s e o l f ’ th ‘ r ou gh n orm al e xp res s ion of
M H C C l a s s I t r i g g N e K r s -c e l l i n h i b i t o r y s i g , n w a l h s i c h s wi tch off act i vat in g s i gn als .
N K -c e l l r e c e p t o r s
Th e N K -c e l l s u rfa ce re cep tors c o m p r i s e t w o f a m i l : i e s
1 . Im m u n o g l o b u l i n s u p e r , f i a m n c i l u y d i n g k i l l e r i m m -l u i n k o e g l r e o c b e u p l t o i r s n ( K I R ; )
a n d
2 . C-t yp e l ect i n l i ke recep t o rs in clu d in g NKG2 D a n d n a tu r a l c y t o t o x i c r e c e p t o r s ( N C R )
A s in gl e s ign al f ro m on e of th es e recep to rs is n ot s u f f i c t i t o e n t r i g g e r e i t h e r th e b e gi n n in g
o r t h e e n d o N f K -c e l l act i vat ion . In s tead , th e t r i g g e r i s t h e r e s u l o t m b o i f n e c d s i g n a l of s th es e
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 5 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
N K -c e l l r e c e p t o [ r B s i a s s o n i e t a l . , 2 0 0 1 ; M a n d e l b o i m & P o r g a d o r , . 2 0 T 0 h 1 e ] m e c h a n i s m s o f
the i n t -c r e a l l u l a r s i g n a ls cas cad es are co m p l e x [ M i d d l e t o n e t a l . , 2 0 0 an 2 ] d n ot cl earl y d efi n ed .
Mid d let on et al . [2 0 0 2 ] h a v e r e c e n t l y d e s c r i b e d o n e m o d e l, w h i c h i s b a s t e h d e i o n n t -c r ellu a lar
s t r u c t u r o e f the s e t w o f a m i ly r e c e p t o r , s i. e. th e i m m u n o-r e c e p t o r t y r o -b s i as n ed e in h ib it or y
motifs ( IT IM) an d t h e i m m u -r n e o c e p t o r t y r o -b s i a n s e d a c t i v a t i o n m o t i f s ( I T A M [Bak ) ker et al . ,
2 0 0 0 ] .
Th e IT IM a r e t h e r e c e p t o r motifs wi th lo n g c yt op las mic tails th at are res p on s ib le f or th e
i n h i b i t o r y s i g n a l s a s s o c i a t e d w i t h r e c o g n i t i o n o f M H s, C w c l h e a r s e s a ts hI e IT m o AM l e c au re l e
t h e r e c e r p m t o t i f s w i t h s h o r t c y t o p l a s m g i v c e r t i s a e i to l s t h a e n d a c t i v a t n als i o . n Al s l i g
reaction s s eem t o b e t h e res u lt of th e b alan ce b etween th es e in h ib itor y an d activati on s ign als .
M i d d l e t o n e x ined p l a th e regu lat ion b y m ean s of th e l e n g t h o f t h e i r c y t o p l a s m i . c I t TAM a i l s , i . e
h a s s h o r t IM e r h a s a l o n d g e r / d I e T e p e r c yt o p l a s m i c t a ils. Acti vation s ign als can b e b locked b y
i n h i b i t o r y s i g n a l er s or i mo n re d e pe eri p p h eral level s of intra-cellu lar cas cad e wh e n th ere are
en ou gh in h ib it or y s i gn al s fr om th e IT IM to o verc o me acti vation s ign als f r o m . t B y h e I T A M
t h e se c o m p l e x m u s , th t e u N K a -c l e l l m a intains m e c h i t a s n b a i l a b s n e c t e w m e e n i n s u f f i c i e n t
reaction a g a i n s t t h e t a r g e -s t e l f ( n o r n a l t -s e l r f) e a d n d o v e r-r e a c t i ext o n en d in g to th e ‘s e l f ’.
T-l y m p h o c y t e s
T h e -l T y m p h o c y t e s a r e o n e o f t h e p r i n c i p t a h l e a d c a p e t l i l v e t c y e p l e l s u l i a r n i m m u n e
s y s t e m . T h e y m a k e u p 0-85% a b o u of t t h6 e mon on u cl ear cell fra ction in n or mal p erip h eral
b l o o d ( p e r i p h e r a l b l o o d m o n o n u c l e a r c e l l s : P B M . C s ) T h e r e a r e t w -l o y m p s h o u c b y t s e e s: t s o f T
35-80 % o f a r e t h e l h p e r T-l m y m p h o c y t s e ( T h . ) w h i c h o r c h e s t r a te b o t h c e l l r u an l d a h u moral
immu n ol o gi cal res p on s es b y p r od u cin g c yt o k i n e s a n d b y c e l l-cell c on tacts v i a -c e l T l r e c e p t o r
(T C R ); a n 20-6 d 5 % of th em are c yt ot o xi c T-ly m p h o c y t es ( C T L ).
T h e h e l -l p ymp e r h oc T yt es h a ve b een fu rt h er su b d i v i d e d i n t o t h r e e p e s p (T h e a n b o l t e y 1 ):
1 . T yp e I h el p er T-l ymp h oc yt e (Th .1 );
2 . T yp e II h e l p e -l r ymp hT oc yt e ( T h . 2 ); an d
3 . R e g u l a t -l o r y m p h T o c y -r t e g e ) ( T
accord in g t o th ei r rol es in d efen ce [ J o n u l e i t & S c h m i t t , 2 0 0 3 ; M c H u g h & S h e v a c h , 2 . 0 0 2 ]
Th e Th .1 cel ls p ri n ci p al l y orch es trate cell u lar immu n it y, th e T h . 2 c e l l ab s le e h un moral
i m m u n i t t y o r e a c t a g a i n s t s, an p a d t th h e o g T-re e n g cel ls mai n l y r egu late t o s u p p res s exces s ive
in flammat or y rea ct i on s i n cellu lar im mu n it y.
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 6 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
I n c o n t -cells r a wh s t ich can t at o tack N ‘n K o n -s e l f ’ i n a -s n o pn ecifi c m an n er as d es cri b ed
a b o v e , each T-l y m p h o c y t e h a s a u n i q u e r e c o g n i t i o n a g a i n s t a s p e c i f i c a n t i . g Th e n is s p eci fi ci t y
o f a n a n t i g e n w o u r s k i s n g th b e y M HC cl as s I (f or c yt ot o xic T-l y m p h o c y t ) e o r clas s I I (fo r
he l p e -l r ym p T h o c yt e) m ol ecu les . Becau s e an y ‘n o n -s e l f ’ p a r t i c l e s c a n b e , a th n e total a n t i g e n
p op u lat ion of T-l y m p h o c y t e s c o l l e c t i v e l y b e a r s a h u g e r e p e r t o i r e o f , an r e d c e mos p t o t r of s th em
in c i r c u l a t i a r o n e i n a c t i v e o . r T h e r s e s r t e p i e n r g t o i r e a s r e t h e r e s u l t of s th e h igh le vel o f
d i v e r s i t y i n p r t o t h o e t y p e a n t i g e n r e c e p t . o r T h i s m he an c is m in p rod u ct ion of h u ge variet y o f
a n t i g e n s -cell p e c recep i f ti o rs c is sT imi la r to th e mech an is m in p rod u ction o f a wi d e ran ge o f
a n t i g e n s p e c i f -c i ells c an a d pn las t ma i b cel o ls d . i e s b y B
R e c o g n i t i a n o d n e l i m i n a t i o n o f s p e c i f i c p a t h o b g e y -l n s y T m p h o c yt e s
T h e r o l -l e y m o p f h o c y T t e s i s t o r e c o arra g n i n s g e , a n e d i t h e r , d i r e c t l y o r i n d i r e c t l y t o
elimin at e f orei gn p at h ogen s . Th is rec ogn i tion of p r e-e x p o s e d a n t i g (rec e n all a n t i g ) e is n b as ed
o n a h u g e v a r i e t y o f a n t i g e n r e c e p t o r s , of a n p d a t h t o h g e n e d ep l i en m di s n on a t th i e o ab n ilit y
of rap id p rol i ferat i on o f on e s p ecificall y r ecogn is ed s et o f l ym p h oc ytes . T h e p r o l i f e r a t iv e
res p on s e o f -l ym T p h oc yt es c o n s i s t s o f f o u r p r o c e s s e s :
1 . Re c o g n i t i o n e o f o r t e h i g n p a t h o t g e o n m a t a p c r h e-exp os ed / r e c a l l a n ; t i g e n
2 . Act i v a t i n g c e l l -S-G c y c l 2 e -M ) ( G p 1 r o g r e s s o i f o n t h e o t yp n e o f c e l l m a t c h ; e d
3 . Ac t u a l c e l l d s i an v d i p s r i o l n i f e r a ; t i a o n n d
4. Ap o p t o s i s o f e x c e s s i v e c e l l s g e n e r a t e d t a h b r o v u e g h p r t h o e l i f e . r a t i o n
T h i s p r o c -l e s y m s p h o c f y t e T p r o l i f e r a t w i n o n t o i o s c c u k r n a o l s in o p eri p h eral
l ymp h oc yt es b ot h i n v i an v o d e x v i , v o p a r t i c u s l i g a n r i f l i c a y n t in r e s p o n s e t i o n v i s timu t r o lat ion w i t h a m i t o g e n , a s u p -a e n r t i g e n , o r s p e c i f r i e c a l l an ti g en s [A n t i a e t a l . h med 2 0 0 3 ; K a e
2 0 0 3 ; S e d e r a n d A h m e d ]. 2 0 0 3
1 .2 .1 .2 C o m m u n i c a t i o n b e t w i e m e m n u n e c e l l s
Immu n e cells (e.g . N K -cells, l y m p h o c y t e s a n d p h a g o c y t e ) s c om mu n icat e wi th eac h ot h er
e i t h e r d i r e c t l y b y c e l l-c e l l c o n t a c t, o r i n d i r e c t l y v i a v a r i o u s s e c r e t e d m , o wh l e ich c u l ie ns teract with cel l s u rface mol ecu les o r i n t -c r e a l l u l a r ( c y t o p l a s m i c o r n u c l e a recep r ) tors .
Man y s u rface mar kers (rec ep tors ) h a ve b een id en tified an d n amed accord in g to th e
c l u s t e r s o f d i f f e r e n t i a t i o n ( C D ) s ys te m [T a b l e ]. 2 Th is al lows cel l t yp es (p h en ot yp e s ) to b e
i d e n t i f a i c e c d o r d i n g t eir o e x t p h r e ss i o n o f c e l l s u rface mar kers , e. g. he l p e -l r y m p T h o c y t e s
( C D 3 + C D 4 + ), c y t o t o -l x i y m c p h o T c y t e (C D 3 + C D 8 + ) , -cells B ( C D 1 9
+ ) , -cells N K ( C D 3
- C D 5 6 + )
an d N K T -cells ( C D 3
+ C D 5 6 + ). T h i s i d e n t i f i c a t i o n c yt c o m a e n t er
b e p e r f o
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 7 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
w h i c h d e t e c ts fl u ores cen t l y con ju gated s p ecific an tib od ies b ou n d to u n iqu e C D m a r k e r s /
m o l e c u l e s e x p r e s s e d o n t h e c e l . l s u r f a c e
Fo r e xamp l e, N K -c el l s are ch a racteris ed b y th e e xp res s ion o f C D5 6 mol ecu les on th e
s u r f a c e a n d t h e a b s e n c e o f a c o m m o n l y m p h o c y t e m a r ( k e r C D3 ) w h i c h d i s t i n e s g u i t i fro s h m
a n o t h e r c y t o t o x i l c y m p h o c y t e -p s o p u u b l a t i o n (N K T -cel ls : C D 3 + C D 5 6 + l ymp h oc yt es ) [Sea man ,
2 0 0 0 ] . Fu rt h er C D 1 6 c a n b e u s e d t o u d i s t h i n g b e -cell t w se u be s et n s , i .e. N t K h e c y t - o t o x i c N
Di m Br i g h t
c e l l s ( C D ) 5 6 e xp res s C D1 6 wh il e t h e r e g -c u e l l s a (C t D 5 o 6 r y ) a r N Ce K D1 6 n egat ive [s e e a l s o T a ]. b l e 2
T able 2: C D e x p r e s s i o n N K b -c y e l l s and lymphoc yt es
N K -c e lls C D 3 (-) & C D 5 6 +
T-l y m p h o c y t e s C D 3 +
B-l y m p h o c y t e s C D 1 9 +
C D 3 + +
& C D 5 6
C y t o t xi o c C D 5 6 D i m & C D 1 6 +
R e g u l a t o r y
N K T -c e l l
C y t o t o x i c
C D 5 6 B r i gh t & C D 1 6 (-)
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 8 - I m p e r i a l o C n o d l o n l e g e L
C D 8 +
H e l p e r C D 4 +
Th e s ecret ed m ol ecu les wh ich act as intra-c e l l u l a r m e s s e n g e br etween s im mu n e cel ls are
k n o w n as c yt o ki n es . C yt o k i n es con s is t of t h r e e g rou p s [s e e a l s o T a ]: b ( l 1 e ) p 1 r -i o n flammat or y
( I -1 L , -6 I , L T - N F , I - N F e t ); c ( 2 ) T h . 1 -2 , ( I -1 I 2 L L e t c . ); an d (3 ) T h . 2 -4 ( , I -1 L I 0 L e t c . )
c y t o k i n e s. Th e y h a v e b e e n c l a s s i f i e d i n ct yto o ki t h n e f a m i l i e s u c h a s In t e r l e u k i n ( s IL) ,
In t e r f e r o n s (IN F), Co l o n y s t i m u l a t f i a n c g t o r s ( C S F ), Tu mo u r n ecr o s is fa cto r s ( T N F ) a n d a
ran ge of c h e m o k i n e f a m i l s i [ J e a n e w a y e t a l . , 2 0 0 . 1 ]
As n e w c y t o k i n e s w e r e d i [ s J a c n o e v w e a r y e d e t a l . , 2 0 0 , 1 th ] e d is ti n ct ion s b et ween
v a r i o u s t y p e s o f e n d o g e n o u s m o l e c , u w l h e i s c h a r e u t i l i s e d f o r c e l l-c e l l c o m m u n i c , a bt ecame i o n
in creas in gl y a mb igu ou s d u e to o v e r l a p p i n g f u n c t s i [T o n a b l e ]. 3 In i t ia l l y th e s e m l ecu o les were
c o n s i d e r e d t o b e p r o d u c e d b y s p e c i f i c an c d e l to l s af fect s p e c i f i c c e l l o s n l y i n e a c h . o r g a n
Recen t e v i d e n c e, h owev er, h as reveal ed t h a t t s h e m o l e c u l e s c a n b e p r a o d v u a c r i e d t y of b y
d ifferen t c e l l s tha a n d t t h e i r recep to rs a r e e x p r es e d b y a vas t r a n g e o f t yp es of cel l s in d ifferen t
org an s ys t ems [ Han s en et al ., 1 9 9 8 ; Marz et al., 1 9 9 9 ; Miller et al ., 1 9 9 4 ; Tu rn b u ll & R ivie r,
1 9 9 9 ] .

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
H o r m o n e s
T able 3: D e f i n i t i o n s o f v a r endogenous i o u s m o l e c u l e s
Ch e m i c a l s u b s t a n c e produce s d i n a r n g a n o o r g l a n d i n t h e b o d y t h a t a r e
s e c r e t e d into t h e b l o o d a n d c a r r i e d t o o t h e r o r g a n s o r p a r t s o f t h e
N e u r o t r a n s m i t t e r s
Ch e m i c a l s u b s t a n c e s r e l e a s e d f r o m n a p n s e u s r o t n s h a t i tn o b i s n y d
( C a t e c h o A c l e t a y l m c i li h n o e n ) e s c o r r e s & p o nd ing r e c e p t o r s o n ne a r b y c e ll s u r f a c e s o r a c t iva te s e c o n a d r y
m e s s e ng e r c a s c a d e, i . e c h a n n e l s , p u m p s , k i n a s e s , o r p r o t e a s e s
C y t o k i n e s
P rot ein s t hat ar e t he co r e o f co mmu nicat io n bet ween im mu ne ce lls
t h e m s e l s , v a n d w i t h c e l l s b e l o n g i n g t o o t h e r t i s s u e t y p e s
���� .
C h e m o k i n e s
P rot ein s t hat sig na l leu ko c yt es t o mo ve in a spec if i c d ir ect io n; in o t her
���� . w o r d s , a c l a s s o f c h e m o t a c t i c c y t o k i n e s
E i c o s a n o i d s
B i o s y n t h e s i m s o e l d e c u l e s f r o m a r a c h i d (p o o n i l c y-u nsat a c i ur d at ed
( A r a c h i d o n i c a c i d d e r i v a t i v e s ) f a t t a c y i ), d i . e . p tr agla o s nd in s, pr o st ac yc lin s, t hr ombo xa ne s,
leuk o t r ie nes et c. ; i n o t h e r w o , r a d cs las s o f o xyg e nat ed hyd r o pho bic c y t o k i n e s
C o m m u n i c a t i o n a n d i n t e r a c t i o o r n g a s n y b s e t t e m w s e e n
Th e p ri mar y o r g a n s y s t e m s wh ich are d i s t r i b u t e d t h r o u g h o u t an d t h in e wh b io ch d y
me d i a t o rs a r e n o t-r e s t r i c t e d i n ar l e o th c e a t n ervou i o n s s ys te m, th e en d ocrin e s ys te m an d th e
i m m u n e . Th s e y ar s e con t se id m ered to f o r m u l a t in e d ep en d en t c e l l -cell c o mmu n ication
ne t w o r s k b y va ri ou s s ign al tran s p ort ati on s ys te ms ( e.g . e l e c t r i c a l s ign als an d m o l e c u l e s ), an d
th es e com mu n i cat i on n et works are s h o w n to h ave th eir own in d ep en d en t regu latory
m e c h a n i s m s i n ing c l u c d o u n t e r r e g u l a t i o n , b u f f i e s r m i s n a g n d m / o e r c h f a e n e d b a c k m e c h a n i . s m s
F o r e x a m p l , e in th e au ton omi c n erv ou s s y s , t h e m s y m p a t h e t i e c p aras a n d ymp t h at h et ic s y s t e m s h a v e o p p o s i t e e f f ; e th c t e s s y m p a t h e t i c n e r v o u s s y s t e m s u p e p s r e th s s e p arasym p at h et ic n ervou s s ys t em an d vi ce vers a [ B o e r e e , 2 0 0 2 ].
In th e en d ocri n e s y s , t h e m h y p o t h a l a m -pituitary-ad u s ren al ( HP A) axi s h as the
i n t e r a c t i m v o e d u l a t i , o n n a m e ‘c l o y r t i c o t r o -r p h e i l n e a s -fact i n g or (C R F) – a d r e n o c o r t i c o t r o p -h
i c
h o r m o n e ( A C T H ) – g l u c oc o r t i c o i d ( c o r t i s o l )’ i n m od h u um lat a in on . Th is ‘C R F -A C T H-c o r t i s o l ’
mod u lat i on h as feed b ack mech an is ms , b y wh ich in creas ed level s o f c o r t i s o l s ec rete d fro m
a d r e n a l g l a n d s s u p p r e s s e s p r o d u c t i o n o f C R F a n d [Ts A ig C os T H & Ci hn rou t sh os e , b r a i n
2 0 0 2 ] . T h i s m o d u l a t i o n a l s o c o n t a i n s b u f f e r i n g m e c w h a h n e i r s e th m e s le vel s o f f r ee co rt is ol can
b e m a i n t a i n e d i n a n a r r o w w i n d o w r a n g e w i t h a m i n i m u m a s t i i n m t e h e o f o v e r f l u c t u
f o l l o w i n . g Th e l e m v e l c o f h f r e a e c n o r t i s o s l i n m s e r u m d e p e n d s o n t h e r a t o i o f c ort is ol t o
c o r t i s o l b i n d i n g ( g C l B o G b u ) sl o i th n at a s u dd en ch an ge of f ree c ortis ol level can b e b u ffered
b y c h a n gi n g i t s h c o r t i s o l-C B G rat i o, i . e. p e r c e n t a g e s o f c o r t i s o l w h i c b h i n d to th e C B G
[ M c E w e n e t a l 7 . ] .
, 1 9 9
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 9 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
In th e i mmu n e s y s , t c o u e n t m e r-r e g u l a t o r y m e c h a n i s m s o T f h . t 1 h c e l l s a n d t h e T c h e l . l 2 s
wor k to mai n tai n lon g ter m b alan ce b etween t h [ e K i m d d , 2 0 0 3 ], i . . Th e .1 (cel lu lar ) c yt oki n es
c a n s u p p r e s s T h . 2 ( h u m o r a l ) c y t o k i n e p r o d u c t i o n . a n d v i c e v e r s a
F u r t h e rm ore , it h a s b e e n r e v e a l e d t h a t c e a l so s c o m m u n i c a te ove r th es e d iffer en t org an
s y s t e m s [s ee b el ow 1 . 2 . 2 f o r t ne h e u r o-e n d o c r i n -i o m m u n e i n t e r a ], c an t i d o it n ha s b e e n
s u gges t ed t h at t h es e n ervou s , en d ocrin e a n d immu n e s ys te ms h ave mu tu al regu lato r y
m e c h a n i s m s b e t w e e n t h e m s e l v e s a s a n i n t n e r u a r -e c o t n i d v o e c r i n -im o mu n e axi s [ El en ko v et al .,
2 0 0 0 ; H a a s & S c h a u e n s t e i n , 2 0 0 1 ; M c E w e n e t a l . , . 1 9 9 7 ]
1 . 2 . 2 N e u r o-e n d o c r i n -i o m m u n e i n t e r a c t i o n
T h e interact ive n e u r o-e n d o c r i n -i o m mu n e axi s h as oft en b een d is cu s s ed in th e con text o f
s tres s res p on s es [ B e s e d o v s k y & d e l R e y , 2 0 0 1 ; B i o n d i , 2 0 , 0 1 n a ] d i t h as b een p rop os ed th at
p s y c h o l o g i c a l s t r e s s c a n m o d u l a t e t h e i m m u n e v a s r i y s o t u s in e m teract v i ia ve mec h an is ms in this n e u r o-e n d o c r i n -i o m m u n e a x i s [ M o y n i h a n & S t e v e n s , 2 0 0 1 [ ] F i g u r e 2 ].
F i g u r e 2 : S c h e m a o f -e t nd h o e c r in n e o u -im r o mu ne int er act io n.
( H P A : h y p o t h a l a m -p u s i t u i t -a a d r y e n a l a x i s , S A M : s y m p -a a t d r h e na t i l-m c e d u l l a m o d u l a t i o n )
1 .2 .2. 1 B r a i -t n o-im m u n e p a t h w a y
I n re c e n t d e c a d s, e t w o m a j o r a x h e s a v e b een p r o p o s e d a s a n i m p o r t a n t s p i a n t h w e a y
s t r e s s r e s p o : n s ( 1 e ) t h e sy m p a t h e t i c -a d r n e e n o-med r v u ll o a (S u AM) s a n s d (2 y ) s th e t e m
h yp o t h a l a m u s -pituitary-a d r e n a l ( H P A ) s a [d x e Kl oet , 2 0 0 0 ; d e Kl oet et al., 1 9 9 8 ; Down in g &
M i y a n , 2 0 0 0 ; e r s , 2 H 0 0 e 3 ; u Y s a n g e & r G l a s & e r , 2 L 0 0 a [ 2 F ] i m g m u r e 2 ]. Th is s e ct ion in trod u ces th e p a t h w a y f ro m th e b rai n to th e immu n e s ys tem [Elen k ov et al. , 2 0 0 0 ; Lawren ce &
K i m , 2 0 0 0 ].
P h . D . a t U n i v e r s i t y o f L o n d o n - 3 0 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Th e ‘f i g h t o r f l i g h t’ res p on s e [C an n on , 191 4 ; C ann on , 1 9 32 ; C a n n o n , 1 9 3 4 ] an d emoti on s
like an xi et y an d / or fear [ L e D o u x , 1 9 9 8 ] are k n o w n t o b e a s s o c i a t i n e c d r e a w s e i d t a h c t i v i ty in
t h e s y m p etic a t h n e r v o . u h s e T r e s a r y e s t p t r w i o e m a m pr ath y wa ys b y w h i c th h e s ymp at h et ic s ign als are c on ve yed t o ta rget or gan s [ E l e n k o v e t a l . , 2 0 0 . 0 ] O n e p a t h w a is y d i r e c t ura n e l
c o n n e c t i o n s, w h e r e n o r e p i n e p h r i n f u e n c t io n s a s a n e u r o t r a n s m a i ne t u r t a l e t r e r m i n a l. Th e
o t h e r i s k n o w n a s t h e s y m -a p a d t r h e n t o-m i c e d u l l a ( S A M ) p a , t wh h w ere a y e p i n e p h r i n (as e a
r e s p o n s e t o t h e s y m p a t h e t i c n e u r a l a c t i v i t y ) r e l e a s e d f r o m t h e a t d r e a n v a e l l g s l a n t d h s r t o h u e g h
b lood s t r a e n d a c m t s a s a h o r m i n o n v e a r i o u s o r g a s. n F o r e x a m p l , e th e symp at h et ic n eu ral
fib res d e s c e n d f r o m t h e b r a n i e n u ral i tn ermi t o n al b ot h in th e p rima r y l ymp h oid ti s s u es (b on e
m a r r o w a n d t h y m u s ) t h se a econ n d d ar y l ym p h oi d ti s s u es (s p leen an d l ymp h n od es ) [ Felten &
F e l t e n , 1 9 9 4 . ] I m m u n e c e l l s t h e elves m s h ave al s o b een r e p o r t e d t o e x p r e catech s s o lami n e
r e c e p t o r s, b u t th ei r p r o f i s l a e r e u n i q u e, i . . N e K -c e l l s h a v e h i -d g e h n s i t y a n d -a h f i f g i h n i t y -2- b e t a
a d r e ner g i c r e -c c e l p l t s o h r a v s e -d , h i e g n B h s i t -affin y it b y, u an t d T-c l e l l o s w h a v -d en e s it y l o w
a n d -a f l f o i n w �[ i t A y n s t e a d e t 9 9 a 8 l ] . . T , h i s 1 i s i n l i t n h e fin e dw in i gs t h th at c a t e c h o l a m i s, n e
n o r e p i n e p h r i n e a n d e p i n e p h a r c i t n i e v a t e t h e i m m u n e r , e in s p clu o n ds ie n g an in creas e of N K -
c e l l s a n d -cells c y t o i t n o c x i r c u l [ H T a e t n i n i o g n e t a l . , 2 0 0 an 0 ] d an in creas e of p r o-
in f l a m m a t o r y c y t o k pi rod n e u ct ion [ E l e n k o v e t a l . , 2 0 0 . 0 T ] h i s se r i e s o f e v i d e sn tron c e gl y
s u g g e s t s that th e s ymp at h et ic n erv ou s s ys tem ( p a r t i c u l a r l t y h e w S i A t M h a x ) i ds ire ctl y
c o m m u n i c a t s e w i t h i m m u n e c e in l l th s e b r a i -t n o-i mmu n e p at h wa y.
O n t h e o t h e r h o a r m n d o , n e s h i n t h e h y p o t h a l a -pituitary-a m u s d r e n a l ( H P A ) a x i s ha ve als o
b e e n con s id ered to p l a y a i m n p o r t a n t r o l e a s c o n n e c t o r s o mr od u lat ors b et ween th e b r a i n a n d
immu n e s ys tem [ F l i e r & U n d e r h i l l , 1 9 9 5 ; R e i c h l i n , 1 . 9 Cortis 9 3 ] ol , th e mai n s ecret ed h ormon e
t o t h e b l o o d s t r e a m i n t h e H P , is A a b x e i l s i e v e d t o m b e a j o a r st r e s s-r el a t e d h o r m o n e
[ H u c k l e b r i d g e e t a l . , 1 9 9 8 ; R o h l e d e r e t a l . , . 2 It 0 ha 0 1 s ] b e e n d emon s trat ed th at th e maj or
immu n e or gan s , i .e . s p l een an d th ymu s , a n d immu n e cells th ems elves ar e rich in c orti s ol
recep tors [ M i l l e r e t a l . , 1 9 . 9 T 4 ] h e e f f e c t o r f t i s c o l u p on in d ivi d u al t a r g e t c e l , l hs o wever , is
s u g g e s t e d v a t r o y f r o m s u p p r e s s i v e t o , s i t . . si ue m p pu res l a st ive, o r py rep arat iv e, pe r m i s s i v e a n d
s t i m u l a t o r y a c t i [ o S n a s p o l s k y e t a l . , 2 0 0 . 0 T ] h e v a r i o u s facto rs c o n t r i b u t ing to th is d ifferen ti at ion i n c l u d : e
Ty p e s o f r e l t e t a v r a g n e t c e l l s a n d t h e i r c o r t i s o l r e c e p t r o r f i s; l e
Timing o f s e c r e t , i do un rati on of e x p o s u r e, a n d c o n c e n t r a o t f c i o r t n i s o l; a n d
Com b i n at i o n w i t h c a s c a d i n g s e c r e t i o n s oth o f er m o l ecu les (h or mon es an d
c y t o k i n e s ).
P h . D . a t U n i v e r s i t y o f L o n d o n - 3 1 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
I n a d d i t i t o n t h i s c o m , p l t e h e x e x i a t c t y mech an is ms a t t h g e n e l e v e l a re al s o yet to b e
mad e cl ear . Fo r e xamp l e, co rtis ol is kn o wn to b e an tag on is tic a g a i n s t th e n u c l e a r f a c t o r k a p p
( N F B ) [ C h r o u s o s , 1 9 9 5 ; G o u l d i n g , 2 0 0 , 4 ] w h i is c h a k n o w n act i vat o r f or th e tra n s crip tion of
pr o-inf l a m m a t o r y c y t o k i n ( e s I -1 L , -6 I a nL d T N F - ) [ B a r n e s , 1 9 9 7 ] as well as a g e n o m i c
inhibitor a g a i n s t t h a e p o p t o t i c c a s s c a [ d K e a r i n & L i n , 2 0 0 . 2 B] y c on tras t , th e c o r t i s o l -i n d u ced
g e n e p r o d u c t s a r e k n o w n t o c o m a vp as r i t ran s e ge of p r o t e i n s i in n c g l th u e d An n exi n I, wh ich h as comp reh en s ive a n t i -i n fl am mat or y intra-c e l l u l a r s a c [ G t o i u o l d n i n g , 2 0 0 4 . ] N e v e r t h e l e s s , t h
evid en ce s t r o n g l y u s p p o r t s t h e c o n c l u t s h a i t o t n h e m e d i a t o or f s th e HP A axi s (p art icu larl y
cortis ol ) can e xert d irect in fl u en ce u p on i m m u n e c e l l s i n t h e -t b r o-i a mmu i n n e p at h wa y.
F u r t h e rm ore , i n v i v l o a b o r a t o r y s t r e s s s t u d i e s t h a h v a e t t i h l e l r e u c s o i t n s r i s a t e t n e t d
o r d e r of res p on s es in th e ch an ge levels of m e d i a t o r s b etwe en t h e S A M a n d t h e H P A , a x e i s . . an e
in creas e of co rt i s ol l e vel s was ob s erved a fter an in creas e of catech ola min e level s [ C low et al . ,
1 9 97 ; C l ow et al ., 2 0 0 0 ; Hu ckleb rid ge et al., 1 9 9 8 ; Mad d en , 20 01 ; R oh led er et al., 2 0 01 ;
U c h i n o e t a l . , 2 0 0 . 1 T ] h i s su g g e s t s t h a t c a t e c h o l a s m ma i n y e p r om ot e c ort is ol s ecr etion , s o that
t h e s e t w o m a i n a x o e f s t h e b r -t a i o-i n m m u n e p a t h w a y i n t h -n e e p u s r y o-e c n h d o o c r i n -im o mu n e
n etwork ma y al s o co mmu n i cate with eac h oth er.
1 .2 .2. 2 I m m u n e-to-B r a i n p a t h w a y
R e c i p r o c a , l it l has y b een d i s c o v e r th e d at t h e p -i r n o f l a m m a t o r y c y t o k i n e s I ( L-1, I -6 L an d
T N F - ) c a n a c t i v a t e t h e S A M a n d H P A [ B a e x s e s d o v sk y & d el R e y, 2 0 0 0 ; Bu cki n gh am et al. ,
1 9 9 6 ; P e r l s t e i n e t a l . , 1 9 9 3 ; T u r n b u l l & R i v i e r , 1 9 9 9 ; W a n g & D u n . n Th , e 1 9 9 b 9 l ] o -b o d r a i -n
b a r r i e r g e n e r a l l y p r e v e n t s t h e t r a n s p o r t a ti on of lar ge m olecu les f ro m b lo od to th e b rain , h owev er,
th e p r o-i n f l a m m a t o r y in c es y t (p o art k icu la rl y I L-6) we r e s h own t o b e cap ab le o f in c reas in g
p e r m e a b i l i t y o f t -b h r a e i n b l a o r r o i d e r [ C a s t e l n a u e Bu t ckin gh a al m, . 1 9 9, 9 ; 1 9 9 8 ; M u
T u r n b u l l & R i v i e r , 1 9 9 . 9 Fu ] rth er mo re, c yt o ki n es h ave b een s h own to b e r eleas ed f r , an o d m
a f f e c t , i p n e g r i p h e r a l r v n e s a n d t h e b r a i n a s w e pl erip l a hs eral im mu n e cel ls [ Han s en et al.,
1 9 9 8 ; M a r z e t a l . , 1 9 9 . 9 Th ] e p r -infla o m mat o r y c yt oki n es (IL-1 i n p a r t i c u l a r ) w e r e ls a o
d e m o n s t r a t e d t o i n s i t c k i n a e t s e s b e h a v i o u r e ( . g . f e v e r , f a t i g u e , s l e e p a i n d e an s s orexi a)
[ D a n t z e r , 2 0 0 4 ; K e l l e y e t a l . , 2 0 0 3 ; V o -C l l m o n e n r a , 2 0 0 1 ; W a t k i n s & M a i e r , 1 9 . 9 With 9 ] th e
f i n d i n g t -1 h a recep t to t rs h he ave I al sL o b een fou n d on n eu ron s an d glial cells , p articu larl y
d e n s e i n e ht ip h p ocamp u s [ Cu n n i n g h a m & D e S o u z a , 1 9 9 , 3 i ] t w a s su gges ted th at th ere is a
d irect in teract ion b et ween th e im mu n e cells a n d t h e b r i n a i t n h e i m m -to-b u n e rai n p at h wa y
[ B e c h e r e t a l . , 2 0 0 0 ; M a i e r & W a t k i n s , 1 9 i 9 n 8 ] t h e p -n s y e c u h r o o-e n d o c r i n -i o m m u n e n e t w o r k
[ F i g u r e 2 ].
P h . D . a t U n i v e r s i t y o f L o n d o n - 3 2 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
T h e h i p p o c a m p u s a n d th e a m yg d a la, wh i ch p la y a co re role in le arn in g, mem or y a n d
cogn iti on [ B l a n k e t a l . , 2 0 0 , 2 are ] als o k n o w n t o h a v e n imp a o rt an t r ol e in th e s tres s res p on s e
[ d e K l o e t , 2 e 0 r s , 0 2 0 0 3 ; ]. Th e H h ie p p ocamp u s e u s r h a s & b e e s n L ho a w n m t m o b rich e in
c o r t i s o l r e c e p t o r [ s d e K l o e t e t a l . , 1 9 9 8 ; D o w n i n g & M i y a n , 2 0 0 0 ; M i l l e r e t a , l a . n , d 1 9 9 4 ]
c o r t i s o l was s h own to en h an ce mem or y b y me an s of th e g l u c o c o r t i c o i d r e c e p t o r s G ( C R s ) in th e
h ip p ocamp u s [ d e K e l t o e t a l . , 1 9 9 . 9 In ] a d d i t i o n , th e GC R s in h ib ition (b y an tag on is ts ) in th e
a m y g d a l a w a s a l s r o e p o r t e d t o i m p a i r m e m o r y i c n o c n l s u o d l i n i g d a s t r i e o s s n f u l m e m . o Th r i is e s
imp airmen t o f mem or y c on s olid ation w a s s u gges ted to res u lt in d ecreas in g th e leve l s of fear an d
an xiet y [ M c G a u g h o o z e & n d a a R l , 2 0 0 2 ; R o o z e n d a a l , 2 0 0 . 0 F ] u r t h e r m o r , e it has b een
d emon s t rat ed t h at t h e s ymp ath etic n erv ou s s ys te m an d th e HP A a xis man a ged to p r ov oke
an xiet y [ T a n a k a e t a l . , 2 0 0 . 0 ]
H e n c e , it w a s s u g g e s t ed t h a t t h e i m -to-b m u n r e a i n p a t h [ w M a y i e r , 2 0 0 3 ] c a n e x t to e n d
p s y c h o-b e h a v i o u r a l r n s e s p or o ‘m i n d-b o d y ’ in teract ion [ Y u a s a & K a s u l i s , 1 9 8 7 as ] in th e
p s y c h o-n e u r o-e n d o c r i n -i o m m u n e n e t w . o r k
C on s eq u en tl y, it is p r o p o s e d t h a t t h e s e i n -c t e r l l u l a r i n t e r a c t i o n s -cellu a n d i lar n t r a
m e c h a n i s m s each i n level of t h e p s y c -n h e o u r o-e n d o c r i n -im o mu n e n et work en ab le th e immu n e
s y s t e m t o m a i n t a i n h o m e o s t , a i.e. s i s t h i be alan n h ce e a of l t r eact h ion s b et ween in co mp eten t
immu n e res p on s es , wh i ch ma y lead to ma lign an c y o r in fection , an d exces s ive in fla mmati on ,
wh ich m a y l e a d t o -i mmu a u t no e d is eas e or al le rg y.
1 .2 .2 . 3 Ci r c a d i in a th n e n e u r o-e h n d y o c t r i h n -i m o m m u n e n e t w o r k
Ea c h o r g is a kn n o wn to s f y o s l t its l e o w m w n h o m e o s t a t r i e c s t-a l e r t c ycl es . These r e s t-
alert c y c l e s s y n c h r o n i with s e t h e s l e -w e p a k e c y c l [L e a v i e , 2 0 0 1 ]. Th e y h a v e b e e n o b served as
d i u r n a l v a r s i [C a t leri i o ci n et al ., 1 9 9 7 ; Gl as er et al. , 2 0 0 1 ; Mas ch ke & Hech t, 2 0 0 4 ; Saka mi et
a l . , 2 0 0 2 ] o r h a d th ei r own ci rcad ian p a t t e s r [ n Folka rd , 1 9 9 0 ] i n t h e l e v e l s o f t h e i r m . e d i a t o r s
T h e b i o l o g i c a l -wa s ke l e ce ycl p e, a ci rcad ian rh yth m , is origin all y d riven fro m a
p h ys i o l o g i c a l c yc l e o f c h a n g e s i n b o d y t e m p e r a t u r e , i . e . o n e c yc l e o f d i u r n a l c h a n g e s i n t h e s -e
t
p oin t temp erat u re [ F o s t e r & K r e i t z m a n , 2 0 0 . 4 O ] n e e x a m p l e e o f o b t s h e r v e c d i r c a d i a n p a t t e r n s
i n t h e n -e e u n r d o c r i n -i o m m u n e n e t w a o r e k t h e sh ifts in d o m i n a n e c i n t h e b a l of a n c e
i n t e r a c t i o n within s each n e r v ou s , e n d o c r i n e [ La yc oc a k n & d Wi s e i , 2 0m 0m 3 ; u n e s y s t e m
M a r s h a l l & B o r n , 2 0 0 :
2 ]
P h . D . a t U n i v e r s i t y o f L o n d o n - 3 3 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
1 . Th e p a r a s ym p a t h e t i c i s d o m i n a n t o v e r t h e s ym p a t h e t i c a t n i g h , t an d vi ce vers a
d u r i n g t h e d a ; y i n t h e n e r v o u s s y s t e m
2 . A p ea k s ecr et i on o f mel at on in p reced es s leep [ L a v i e , 2 0 0 1 ] an d a cortis ol s u r ge
p reced es waki n g [ B o r n e t a l . , 1 9 -S 9 c 9 h ; w a S l b p e a t e t h a l . , 1 9 9 ; 2 ] a n d
3 . T h . 1 c y t o k i n -2 e ) s are h( igh e . er g at . n i gh I t tL h an d u rin g th e d a y [ B orn et al .,
1 9 9 7 ] a n d t h e y c a n c e n h s l e e i p n d u c t i o w n h i l e T h . 2 c y t -4 o k a i n -d
e s L ( e . g . I
1 0 ) s u p p r e s s s i l n e d e u p c t i o n a n d d t i h s e t s l u e p r e b p r o c e s s [ M a r s h a l l & B o r n , 2 0 0 . 2 ]
It ha s a l s b o e e n s h own th at th e ci rcad ian p at tern s of th es e s e c r e t e d m o l e c u l e s i n - t h e n e u r o
e n d o c r i n -im o mu n e n et work con tri b u te to th e s l e e -wa p ke c ycl e b y p r o mot in g or in h ib itin g s leep
[ M o l d o f s k y , 1 9 9 5 ]. For e xa mp le, pr o-i n f l a m m a t o r y c y t o k i n e s e. ( g. T N F- I -1 L a n d -6) I as L
w e l l a s m e in l are a t o kn n own to in d u ce s leep [Kr on fol & R emic k, 2 0 0 0 ; Kru eger & Majd e, 1 9 9 4 ,
2 0 0 3 ] . In ad d it ion , c o r t i s o l a -i n d n f l p r a o m m a t o r t o y k i c n e y a n t a g o n i s t s e. ( g. I -1 L r a ) a s w e l l as
n egative mo od (e. g. a n x i e t a y n d ep res s ion ) can in h ib it s leep [ S a k a m i e t a l . , 2 0 0 . 2 ]
R ecip rocal l y, d i s o r g a n i z a t i o n o f -w t a h k e c s y l c e l e p h a s b e e n s h ow n t o i n d u c e
al t e r a t i o : n s
1 . In th e le vel s o f th e n e u r o-en d ocrin e h or m on es [ v a n R e e t h e t a l . , 1 9 9 in 4 ] clu d in g
imp airmen t o f mel at on in s ecreti on [ S u z u k i e t a l . , 1 9 9 ; 3 an ] d
2 . In i mmu n e p aramet ers [ C r u e s s e t a l . , 2 0 0 3 ; M o l d o f s k y , 1 9 in 9 5 clud ] in g s h ift in g the b a l a n c e o f T h . 1 / T h . 2 c uy ctio t o k n i toward n e p r Th o d .2 d omi n an ce [S aka mi et al .,
2 0 0 2 ] .
T h e s e a l t e r a t i o n s m a y b e a s s o c i a t e d w i t h e a c h o t h e r s i n c e m e l r a t e o p n o i r n t o w e d a s
s timu lat e Th .1 c yt o ki n e p rod u ction [ G a r c i -M a a u r i o n e t a l . , 1 9 9 9 ; I n s e r r a e t a l . , . 1 It 9 9 h8 as ]
als o b een s h own t h at s l eep d ep rivation , p articu larl y th e rap id e ye mo vem en t (R EM ) s leep
d ep rivat ion , imp ai rs i mmu n e res p on s es [ C a s e y e t a l . , 1 9 7 . 4 Th ] e ‘s l e e p e f f i c ie n c y ’ , i .e. th e
p ercen tage o f t ot al s leep am ou n t in a v a i l a b l e -time s l e e (i p n cl u d in g awake ti me in b ed ), was
s h o w n t o c o r r e l n e a t g a e t i v e l w y i t h t h e c l i n i c a l p a r a m e st en e tin r s g r d e is p eas r e e s ev eri ti es b oth in
c y s t i -fib c r os is p at ien ts [ M i l r o s s e t a l . , 2 0 0 2 ] a n d -i i n f n e c t e H d I p a V nt ts i [ e C r u e s s e t a l . , 2 0 0 . 3 ]
T h e s l e e p e f f i was c i e al n sc o y r e p o r t to e d b e s ign ifi can tl y d ecreas ed in recu rr en t d ep res s ive
p atien ts , an d t h e p ercen t age of th e R EM s leep was in creas ed with in th e d ecreas ed time o f s leep
[ T h a s e e t a l . , 1 9 9 . 5 Th ] is s u g g e s t s t h e i m p o r t a n h c e a l t o h i n m a i an n t ap a i pn rop i n ri g at e
a m o u n t o f t Rh EM e s leep .
P h . D . a t U n i v e r s i t y o f L o n d o n - 3 4 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
In p atien ts wi th d ep res s ion , wh o o f t e r n e p o r t s leep p rob lems , mel at on in s ecretion is
rep orted to b e imp ai red , an d ex o gen ou s melaton in ha s b e e n s h own to res to re s lee p q u al it y an d
mo od [ L e p p a m a k i e t a l . , 2 0 0 . 3 Ex ] ogen o u s mel at on in was als o s h own t o imp r ove mo od an d to
inc r e a s e t h e R E M s l e e p i n d e p d r e ps atien s ts d u ri n g th e n ext d a y of ad min is tration [Bau e r et al .,
1 9 9 5 ; S p a -S t c h w a l b e e t a l . , 1 9 9 a 8 l ] t h o u g h t i h m e p r o v em e n t mi n ood an d in crea s ed amou n t of
th e R E M s l e e d p i s a p p e a r i e n d t h e f o l l o w . i Fu n g rth er, d a y a h igh c ort is ol t o melato n in ratio
( c a u s e d b y i m p a i r m i e g n h t -t i m o f e m n e lat on in s ecret ion ) ha s a l s b o e e n s h own to correl at e wi th imp aired c e l l -med i at ed i mmu n e res p on s e s an d with an in creas e in d ep res s ive moo d [ Fi orin a et
a l . , 1 9 9 9 . ] H e n c e m e l a t , o a n s i w n e l l a s c o r t i s o l a p p e a r e to d h a ve an i mp ort an t r ol e regard in g
s l e e p r e g u l a t i o n i n -n t e h u e r o-e p s n d y o c c h r o i n -i o mmu n e n et wo rk.
C o n s e q u e n t l it y has b e e n s u g g e s t e d t th h a e s l e e p p r o c e s s itself p la ys a n i m p o r t a n t r o l e i n
in teract ion s in th e p s y c h o-n e u r o-e n d o c r i n -im o mu n e n e t w o r [ k Kru eger et al . , 2 0 0 3 ; Mars h all &
B o r n , 2 0 0 2 ].
1 .2 .2 . 4 Ci r c a d i a n d n s u b r j e c h t w i y v e e l t l-b h e i m n g
P s y c h o l o g i c a l l y , t -wak h e e s cl ycl e e p is a rob u s t regu lat or of h u man ale rtn es s [ Hu ll et al.,
2 0 0 3 ] . At t h e b e gi n n i n g of s leep , th e b od y red u ces th e in p u t of exte rn al s timu li (n e u ral s en s or y
in p u ts ) an d t h ere i s al s o l es s p h ys ical m o vemen t (n eu ral mot or ou tp u t s ). Th is s leep in du ction
a n d i t s m a i n t be o e n h el a p fu n l c for e c o n a s o l r i d a e ting mem k n o or y w in th e awa k e learn in g
p r o c e s s, s o th at e f f e c t i v e c o g n i t i v e f d au yti n c me t i co an n bi e n p res erved [S tic k gol d et al., 2 0 0 1 ;
S t i c k g o l d & W a l k e r , 2 0 0 5 ; W a l k e r e t a l . , . 2 Al 0 0 5 e ] r t n e s s th a e n c d o g n i t ive e ffect i ven es s in
f u n c t i o n v h e a b e e n d i s c u in s s r e d l a tion to su b j e c t i v w e e l l-b e i n g r a t i n g a s n d q u a l i t y o f l i f e
d u rin g th e d a y t i m e a n d t o s u b s e q u e n t s leep q u a l i t a t y n i g h t. T h e m o s t c o m m o n l y u s e d s e -l
f
rep ort meas u re of s leep q u al it y i s t h P e i t t s b u r g h S leep Qu al it y In d ex (P SQI) [ Bu ys s e et al.,
1 9 8 9 ] .
Sl e e p q u a l , as i t meas y u red b y th e P SQ I, h as b een r e p o r t e d ith t am o ou nc t of o r r e l a t e w
s leep , n amel y th e s l e e p e f f c i y , c i a n e d n w i t h t h e p e r c e n t a g e s o f R E s l M e e p i n t h e t - o t a l s l e e p
time [ M i l r o s s e t a l . , 2 0 0 . 2 Sleep ] q u al it y h as al s o b een s h own to r e p o r t e d t o c o r r e l t a h t e e w i t h
q u a l i -o t f y -l i f [ e C o h e n e t a l . , 1 9 9 , 8 a ] n d it has b een s u gges ted th at imp roved s leep q u alit y ma y
c o n t r i b u t e t o b e t t -o e f r -li fe q u [ Ma l ye i rs t & y Bad ia, 1 9 9 5 ] . R e c i p r o c a l l a yti y , me d r el axat ion exercis e has s h own to imp r ove th e s leep q u alit y [ S h a p i r o e t a l . , 2 0 0 . 3 It ] ha s a l s b o e e n
d e m o n s t r a t e d t h a ut b jects s wi th a h i g h a m p l i t u d e o f a l p h a d a w y t a i v e m bs e rain i n waves , wh ich r e p r e s e n t s a c a l m e r o r r f e mi l a n d x e , sd leep s t sa ign t e ifi can o tl y l on ger an d d eep er [Eh lers et al. ,
P h . D . a t U n i v e r s i t y o f L o n d o n - 3 5 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
1 9 9 8 ] . O n t h e o t h e r , h a d i n d s o r g a n i z a t i o n o -w f ake t h e c ycl s e l w e a e s p f o u n d t o i m p a i r t h e
q u a l i -o t f y -li fe [ E d e l l -Gu s t a f f s o n , 2 0 0 2 ; E d e l l-Gu s t a f f s o n & He t ta , 2 0 0 1 ].
C o l l e c t i , v th e ere l y m a y b e an i n t e g r a t r e l d a t i o n b s e t h w i e p e n n i g h t t i m e w e l l-b e i n g (s leep
q u a l i t y ) a n d d a y t i m e w e l l-b e i n g (q u a l i -o t f y -l i f ), e a n th d e d a yt i me w e l l -b e i n g ma y con trib u te to
th e n i g h t t i m e w e l l-b e i n g a n d v i c e v e r i s a n t h e p -ne s y c u h r o o-e n d o c r i n -i o m m u n e n e t w . o r k
1 .2 .3 P s y c h o l o g i c a l i n p u t i n -n t h e u r p o-e s y n c d h o o c r i n -i o m m u n e n e t w o r k
T h e w o r d ‘S t r e s s’ w a s d e f i n e d b y H a n s S , a e l py he ys ici an an d en d ocri n ol ogis t wh o
in s tigat ed s tres s res earch , a s “ t h e -s n p o e n c i f i c r e s p o n s e o f t h e b o d y to an y d e man d ” [Sel ye ,
1 9 3 6 ] . S e l y e a l s o e m p h ed a s i th s e d is ti n cti on b et ween ‘St r e s s o r’ (th e cau s e) an d ‘St r e s s’ (th e
effect) [ S e l y e , 1 9 7 5 a ].
1 .2 .3. 1 S t r e s s o r
Li fe e ven ts (s u c h a s t r a u m a , d i s e a s e , e x e r a c n i d s l -c i f h e a n g i n g e x p e r i e n c e ) s c h a l l e n �g
e
a n i n d i v i d u a l ’ s c a p a c i t y t o a d a p t t o i n n e r a n d o u s t e r c h d a e l m l a e n s d g s e ma . y T bh e
p h y s i o l o g i c a l l y a r a n o d u / s o i r e n m g o ti o n a l l y t a x i n g , a n d t h e s e e v e n t s m a y l e a d t o c o g n i ive t an d
b eh avi ou ral res p on s es .
P h ys iol ogi cal s tres s o rs (i n c l u d i n g t r a u m a , i n f e c t i o n ) a ffect n d s h ut man a r v a o rgan t i o n
s ys te ms d i rect l y t h rou gh cat ab oli c ch an g es (en erg y c on s u min g ch an ges ). P s ych olo gical
s t r e s s o r s�(s t i mu l i wh i ch arou s e h u man emoti on s ) can als o a ffect h u man or gan s ys tems th rou gh
t h e e f f e c t s o f p s y c h o l o g i c a l s t r e s s , b o t h -n e d i u r o-e e c n t d o l c y r i v n -i i o a m m t u h n e p s y c h o
n e t w o r k (i .e. a p p r a i s a l o f s t r e s s o r a c ts as an i n p u t i n t h e n e ) t w a o n r d k mod b y u lat ion of h u man
b e h a v i o u r i n c l u d i n g e a t i n g h a b i t s , e x e r c i s e , s m o k i n g a n -med d s e l icat f ion .
S t r e s s r e l a t e d -e v l e i n t f s e h ave oft en b een examin ed eith er in h ealth y p op u lation s u s in g
a c a d e m i c e x a m i n a t i o n s w h e r -cells e , iN n K p art icu lar, were meas u red as a s t r e s s-r e l a t e d m a r k e r
[Dein zer & S ch u l l er, 1 9 9 8 ; Glas er et al., 1 9 85 ; Gru zelier, Le v y et al. , 2 0 0 1 ; Gru ze lier, Smith et
a l . , 2 0 0 1 ; Ki e c o l t-G l a s e r e t a l . , 1 9 8 6 ; Ki e c o l t-G l a s e r e t a l . , 2 0 0 [ 1 s ] e e a l s o 1 . 2 . 4 . 2 a n d 1 . 2 . , 4 . 3 ]
o r i n p a t i e n t p o p u l a t i o n i.e. s ( clin ical l y s t res s ed in d ivi d u als ) wh o are p ers is ten tl y e xp os ed to th e
p r e s e n c e o f l -lon i f g e d is eas es . T h e s e life-l on g d is eas es often u s ed in th e literatu re i n clu d e
malign an c y (b reas t can cer i n p articu lar ) [ An t o n i et al ., 2 0 0 1 ; Baid er et al ., 2 0 0 3 ; Bakke et al . ,
2 0 0 2 ; S p i e g e l e t a l . , 1 9 8 9 a ] n d i n f e c t i o n s ( p a r t i c u l a r l y w i t h t e h he u man
h e p a t i t i s v i r u s o r
P h . D . a t U n i v e r s i t y o f L o n d o n - 3 6 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
i m m u n o d e f i c i e n c y v i : r u s H I ) [ An V t on i et al ., 2 0 0 2 ; An ton i et al. , 2 0 0 0 ; C arb on e et al., 2 0 0 0 ;
C r u e s s e t a l . , 2 0 0 3 ; C r u e s s e t a l . , . 1 T 9 9 h 9 e ] HIV in fect i on is a l i -th f e reaten in g d is eas e d irect l y
r e l a t e d t h t e o i m m u e n c e l l , s p a r t ic u la r l y C D 4 -c ells T , s o it ma y b e c on s id ered as a go od
examp le of a life-l o n g s t r e s s o r t o b o t h ’s o n b e i o l o y g an d p s y c h o l o y. g In ad d it ion , s t r e s s has
b e e n s h o w to n d e t r i m e n t a l l y af f e c t th e HIV d i s e a s e p r o g r e [C s s atalan i o n et al . , 1 9 9 5 ; C ol e et al.,
2 0 0 3 ; C o l e e t a l . , 1 9 9 7 ; C o l e e t a l . , . 1 9 9 6 ]
He n c e , th e t w o s u b j e c t g r o u p s ed s for i n v i in v ves o ti gat ion in th is p roj ect were :
1 . Un i v e r s i t y s t u d e , n t f s a c i n g a c a d e m i c e x a m i n a t , i as o n an s exa mp le o f in d ivi d u als
with time-l i m i t e d s u s t a i n e d s , t a r e s n s d t h e p r i m a r y o -c u e l t l s; c o m e m e a s
a n d
2 . H I V-i n fect ed a d u lts, n ot rec eivin g a n t i -re trociral m e d i c a t i , a o s n an ex amp le of
indi v i d u a l with s o n -goi n g d i s e a s e-a s s o c i a t e d s t r e , s an s d th e p ri mar y ou tco me
m e a s u r e w a s -cells. C D 4 T
1 .2 .3. 2 St r e s s p e r c e p t i o n
On e in d i vi d u al ’s p ercep t i on of a p articu la r s tres s or will d iffe r f ro m an oth er’s . Fact ors
a f f e c t i n g s t r e s s p e r c e p t i o n c a n b e c l a s s ifi ed in to th ree cate gori es [ F o l k m a n & M o s k o w i t z , 2 0 0 4 ]
S t r e s s o r-r e l a t e d : i n h e r e n t q u a l i t y ( t y p e ) , i n ; t e n s i t y a n d f r e q u e n c y
E n v i r o n m e n t -r e l a t e d : p h ys i c a l a n d s o c i a l r e s o u r c e s; a n d
In d i v i d u a l -rel at ed : c ogn i t i ve ap p rais al, co p in g s kills , an d p ers on alit y.
A m o n g t h e s thr e e e fact ors , th e i n d i v i d u a l-r e l a t e d f a c t o ar re s th os e m os t d irect l y
s u s cep t ib l e t o p s ych ol o gi cal in flu en ces [ H a n , 2 0 0 2 ]. An in d ivid u al’s ap p rais al of a s t r e s so r h as
two ele men ts [ L a z a r u s & F o l k m a n , 1 9 8 4 : ]
1. Pr i m a r y a p p r a l i (p s erc a ep ti on of a d e m a n d, th reat o r s t i m u lu s ); a n d
2. Se c o n d a r y a p p r a i s a l (j u d ge men t in on e’s cap ab ilit y o f c o p in g w i t h a t h r e a . t )
P rimar y ap p rai s al can b e ei th er n eu tral, b en ign o r t h r e a n t i e n g [Te x t b o x ]. W 2 h en th e
p r i m a r y a p p r a i s a l o f a s t r e s s o r w p a s e r c e i v e d a s th reat , th en con s eq u en tl y t h e s e c o n d a r y
a p p r a i s a l w o u l for d mu lat e an d r e s u l t a cop i n in g a c t i o [ n Laza ru s , 1 9 9 9 ].
P h . D . a t U n i v e r s i t y o f L o n d o n - 3 7 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
T e x t b o 2: x APP RAI SAL O F A S T R E S S F U L L I F E E V E N T
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2 3 2 3 =
T w o t y p e s o op f in c g wi th a th reat h a v e b e e n h y p o t h e s i s e d : ( 1 ) e m o t i -f o o n c us ed and (2 )
p r o b -f o l c u e s e m [ d F o l k m a n & M o s k o w i t z , 2 0 0 . 4 ] T h e s ma e y b e m a i n l y a s s o c i a t e th d e w i t h
levels o f p ri ma r y an d s econ d ar y ap p rais al , res p ectivel y. R e c e n t l y , n a d d i nt al i o in d ep en d en t
c o p i n g s t r a t e g y , -makin m e a n i g n fg ocu s ed , h as b een p rop os ed [ T e x t b o x 3 ]. T e h m e a n i -n
g
m a k i n g-f ocu s ed el emen t was p rop os ed as an in d ep end en t cop in g s t rateg y in wh ich th e p ers on
w e i g hs v a l u e s , b e l i e f s a n d g o a l s t o m o d i f y t h e m e a n i n g s f o u f l a t s t r a e s n s a [F c r t a n i k o l n , 1 9 7 0 ],
p a r t i la c r u l y u n d er s u s t a i n se tres d s th at ma y n ot b e a men ab le to the f i r s t t w e o l e m e n t s [P ark &
F o l k m a n , 1 9 9 7 ]. Fo r e x a m p l e , the m e a n i -m n g a k i n g c o p i was n g i l l u s t r a t e d a s trateg t h e y
caregi vers mos t freq u en t l y rep o rted to em p lo y wh en th e y h ave to c o p e with b eh avi ou rs of
d e m e n t e d c a r -r e c i p i e n t [ s G i g n a c & G o t t l i e b , 1 9 9 . 6 ]
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P h . D . a t U n i v e r s i t y o f L o n d o n - 3 8 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
T h e s e t h r e e c o p i n g s t r a t e g i e s h a v e b e e p n a r i a n p t h r e a g r s into a e t d e th d e con a n d cep t of th e
s e n s e o f c o h e r e n oC c e ) [ A ( n S t o n o v s k y , 1 9 9 3 ], in w h ich s tres s fu l p e r c e p t i c o a n b e al tered an d
r e d u c e d t h r o u g h th ree co mp on en ts [ G e y e r , 1 9 9 7 ]:
1 . C o m p r e h e n s i b i : l To i t m y a k e a s t r e s so r r a t i o n a l, u n d ers tan d able a n d / o r p r e d i c t a . b l e
2 . M a n a g e a b i l : i t y T o b e c o m e c a p b a l e o f i n f l u e ing n c d irect l y u p on a n d taki n g in
c o n t r o l o f h i s / h e r s t r e s s-rel at ed e n v i ro n m e n t .
3 . M e a n i n g f u l n e s : s To ob tai n wort h y a w a r e n e s s c b o y m m i t m e n t in a n d i n v e s t m e n t of
h is /h er own exi s t i n g r e s o u r c es.
It h as b een s u g g e s t e d t h a omp t c reh en s ib il it y can b e con s tru cted t h r o u g h t i h n e d i v i d u a l’s
own th ou gh ts an d th eori es , d e s p i t e a n i n s e c u ituation; r e s that man ageab il it y can b e ach ieved b y
a c t i v e i n f o r -s m e a e t k i n o g n s t r a t e g i e s , b y s o c i a l s u p p o r t a n d b y p o s i t i v e r e in terp ret ation of th e
s itu ation ; an d that me a n i n g f u l n e s s c a n b e creat ed b y a c l o s e-r e l a t s i h o i n p an d a faith (or a b el ief a n d c o n f i c d e n i n o n s e l f / a o n r d s o m e t h i n g g r e a te r ) [ F r a n k l , 1 9 7 0 ] a s w e l l ba y s a b e h a v i o u r a l
c o m m i t m e n t / e f f o r t [ S t r a n g & S t r a n g , 2 0 0 . 1 ]
1 .2 .3 . 3 P s y c h o l o g i c a l t r a i n i n g i n t e r v e n t i o n
S i n c e p s y c h o t h e r a p y b e g a n t o r a as p p a e fo a rmal l y re co gn is ed in terven tion with in
med ici n e (p a r t i c u l a r l y m a m e n o t n a g l h e a l t h p r o f e s s ), i o hn us n d red s of fo rms of p s ych oth erap ies
h ave b een in trod u ced [ R o t h & F o n a g y , 1 9 9 6 . ] In recen t d ecad es , th e s t yl e o f p s yc h oth erap y h as
s h i f t e d i n i ts mai n focu s fr om a p a t e r n a l i s t i c s t y l e a t h ( e r i a . p i e s t-o . ri g en i tv at i ed n g th erap y t o a
c l i e n t / p a t i e n t ) to a n e mp owerin g s t yle (i .e. train in g or p r ovid in g a c l i e n t / p a t i e n t w s e i l f-h t h e l p
/ s e l f-a d m i n i s t r tech a t e nd iq u es in clu d in g s ki ll s to get s u p p ort s o th at th e y can man age s tres s b y
th ems el ves ).
Th e latt er t yp e of p s ych ol o gical in ter ven t ion h as focu s ed u p on a t rain in g as p ect , i .e .
t e a c h i n g s p e c i f i c s k / i t l e l c s h n i q u e s a n d e n c o u r a g i n g c l i / e pn atien t s ts to u s e th es e i n d ai l y li fe
[ B a i d e r e t a l . , 2 0 0 1 ; B a t e y e t a l . , . 2 T0 h0 is 0 ] t yp e of in ter ven ti on aims t o h elp p atien ts red u ce
s t r e s s l e v e l s a n d i m p e r w o v e l l-b ei n g th ro u gh th e mod ificati on of b eh aviou r, co gn ition , o r
emoti on [ M i l l e r & C o h e n , 2 0 0 . 1 Th ] is t yp e of in ter ven ti on in clu d es s tres s man age men t
( b e h a v i o u r t h e r a /or p y c a o n g d n i t i -b v eh e a vi ou ral th erap y [ An ton i et al., 2 0 0 0 ; C ru es s et al.,
1 9 9 9 ; C r u e s s e t a l . , 2 0 0 ), 0 relaxat ] i on me th od s [Gi ll an i & Smith , 2 0 0 1 ; Gru zelie r, Le v y et al .,
2 0 0 1 ; K e e f e r & B l a n c h a r d , 2 0 0 , 2 ] s e l f-h yp n os is or vi s u al is at ion [ Gru zelier, Lev y e t al., 2 0 0 1 ;
G r u z e l i e r , S m i t h e t a l . , 2 0 0 1 ; W h i t e h o u s e e t a l . , an 1 d 9 9 b6 iofeed ] b ack or c on d it ion in g
in terven ti on s [ M i l l e r & C o h e n , 2 0 0 1 ; R a y m o n d e t a l . , 2 .
0 0 5 ]
P h . D . a t U n i v e r s i t y o f L o n d o n - 3 9 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Bas ed on th e a p p r a i s a l t h e o ies r o u t l i n e d a b , o it v c e a n b e h yp o t h e s i s e d t h a t p s ych ol ogical
t r a i n i n g an d p ract ice can al ter s t r e s s f u l p e rc e p t i o ( p n r i m a r y a n d s e c o n d a r y a p p r a i s a l s ) b y
p r o v i in d g altern at i ve or s u p p lemen tal p ers p ectives an d co p i n g s k i l l f s o r s t r e s s f u l l i f e e . v e n t s
Primar y ap p rai s al m a y b e a l t e r e d f r o m a t h r e a t t o a n e u t r a l o r a b e n i g n s t imu lu s b y ad ju s tin g
i n d i v i d u a l r , se in a l ce i on t e’s y p ercep ti on is b as ed on on e’s p ers p ectives a n d exp eri en ce. Th e
se c o n d a r y a p p r a i s a l m a y b e a l t e r e ne d w cop b y in l g e sa ki r ln ls i n g ord er t o s tren gt h en on e’s
cop in g ab il it y t o the s t r e s s f u l p e . r c e p t i o n
Self-h y p n o s i s
A m o n g t h e m a n y p s y c h o l o g i c a l i n t e s r for v e s n e t l f-a i o d n m i n i s t r a t e d s tres s man age men t,
on e ap p roach c o m m o n l y u se d i n c l i n i c a l s t u d i e s i n self-h v o l v e y s p n o s i s t r a i a n i d n g p r a c t i c e
[ Ki e c o l t -G l a s e r & Gl a s e r , 1 9 9 2 ; Ki e c o l t-G l a s e r e t a l . , 2 0 0 . 1 H] yp n os is (b ot h wi th an d wi th ou t
s e l f-h y p n o s i s t r a i n i n g is ) ar gu ab l y on e of th e more accep ted th erap ies with in comp l emen tar y
m e d ici n e [ A f a r i e t a l . , 1 9 9 9 ; S t e w a r t , 2 , 0 0 a 5 n ] d self-h y p n o s i s h as b een s tu d ied as a fo rm of
p s ych ol ogi cal i n t erven t i on for d ecad es [ Gru zelie r, 2 0 0 2 a; Gru zelier , Le v y et al ., 2 0 01 ; Sch u lz,
2 0 0 1 ; S p ie g e l e t a l . , 1 9 8 9 ; W h i t e h o u s e e t a l . , . 1 9 9 6 ]
On e o f t h e u n i q u e p e r s p e c t i v e s i n h y p n is o s th i s e con cep t of th e ‘h y p n o t i c s t ’, a t i.e. e a
state o f m i n d i n w h i c h a p e r s o n ' s n o r m a l c r i t i c a l o r [ G r u s z k e l p i e t r i , c 1 9 9 n 8 a . ] t u r e i s b y p a s
Th e h y p n o t i c s t is a t e u s u a l t l a u y g h t as a n a l t e re d l e v e l o f a w a r e n e s s or a s t a t e o f m i n d w h e r e
on e can gai n mor e c on trol ove r him- o r h ers elf an d on e’s c o g n i t i s o ab n ou t or p erce p ti on s of
‘reality’. Th is ma y in creas e th e c o m p r e h e n s i b i i l n i t h e y c o p i n g s t r a t e g i e ss ee [ ab o ve 1 .2 .3 .2 ].
Self-h yp n os is t yp i cal l y i n c l u d e s a f o c u s in g of at ten ti on , f ol low ed b y men tal an d p h ys ical
r e l a x a t , i a n o d n m e n t a l i m a g e r y o f d e ‘ e p e n i n ’ g in and ‘a b s o r p t i ’ o into n a h yp n ot ic state. As a
‘s u g g e s t i ’ o in n a h yp n ot ic state, at ten ti on f o c u se d o n e x e r c i s e s o f -c on a n trol x i , e gt uy id ed
i m a g e r y o f h e a l nt d h th e a f e e l i n g s o f c o n f i d e n c e a n d h a p p s , i i.e. n e s an in creas e in i n n e r s e n s e o f
e m p o w e r m e t. n Th is p ro ces s a i m s t p o r o v i d e p in c g o s ki ll s to i n c r e a s e t h e m a n a g e a b i l i t y
[ 1 . 2 . 3 . 2 . ] F o r t h e p u r p o s e o e f n h a n c ing the man age ab il it y, s o me skills f r o m t co h e g n iti ve
b eh avi ou ral th erap y (C BT ) we re als o p ro vid ed as a s u p p l e m e n t a r t e y c h n i q u in e thi s p r o j e c t
[A p p e n d -2i]. i x A
J o h r e i
T h e o t h e r t r a i n i n g i n t e r f or v e n a t s e i l f-a o n d m i n i s t r s a t r e d a t e g a y p p l i in e d this p r o j e c t s w a
J oh rei, a J a p a n e s e n o n-con tact h e a l i n g h i m c h e l t o o s h k o s i d m i l w a r t o -o t n h -o e f -h l a n y d i s
n g
P h . D . a t U n i v e r s i t y o f L o n d o n - 4 0 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
t e c h n i q u e s. J oh rei is cl as s ifi ed u n d er s u b tle en erg y m ed ici n e a n d a s categ a or y o f
comp lemen tar y med ici n e [ C l a r k e , 2 0 0 0 ] b e c a u s e i t d e a l s w i er t y h of ‘h i m e a l g i n -light’ g or
u n d i s c o v e r ‘vital e d e n e r g y’. Du ri n g a J oh rei s es s ion , th e p ractition er vis u alizes a s p iritu al
h e a l i -l n g i g h t c o m i n g f r o m a n i m a g i n a r ( a y s s i f o u l r i g c h e t c o m e s f r o m t h e S a u n d ) t r a n s m its
th is to th e reci p ien t th rou gh th e p alm of h i s / h e r o u t s t r e t c h e . d As h a wit n d h ot h er s u b tl e en erg y
m e d i c i n e m e t h o d s l Th i erap k e eu ti c tou ch [ M e e h a n , 1 9 9 8 ; O ' M a t h u n a e t a l . , 2 , 0 Ki 0 2 [C ] h an g,
2 0 0 3 ] or Sp iri tu al h eal in g [ P a t t e r s o n , 1 9 9 8 , ] J oh rei h as it s own p h il os op h ical b ack grou n d , in
o t h e r w o r d , s J o h r e i p r o v i d an e s alte rn at iv e p ers p ect ive o f s tres s fu l life even ts .
Th e phi los op h ical b ackgr ou n d o f J o h r e i i n c l u d e k s e y p t r w i o n c i p l e s a i m i pn l y g t o s u p
altern at i ve p ers p ect i ves :
1 . ‘P r o c e s s o f P u r i f ’ i c w a h t i c o h n e n c o u r a g e s in g c o h n a e n ’s g p ers p ect ives d u ri n g
s t r e s s f u l a n d / o r d i f f i c u l t p , se hr i iftin o d s g fro m f ocu s in g on n e g a t i v i t i e o s f th e mo m en t
to f ocu s i n g u p on fu t u re ou t com es wh en t h e p r o b l e m p e r i o d is o v e r; a n d
2 . ‘I Z U N O M E’ w h i c m h e a n s a d yn ami c s tat e of h arm on y in a p p r o p r i a t e t an i d m i n g
b a l a n ce b e t w e e n t w o d i c h o t o m i s e d c o n c / e p a t t s t i t u , d e.g. e s b e t w e e e n n d e a v o u r t o
p e r s i s t m a k i n you g r own d es ti n y wi th ‘M a k o t o’ ( s i n c e r i t y , i n t e g r i t y , t r u t h a n d l o v e
u s e d f o r o ’s n e s e l f a w a r e n e s s ) [ H a r d a c r e , 1 9 8 8 ] an d d e t a c h m e n t ‘l t e o t ’ g (tru o s t in n atu ral t i me cou rs e wh i ch is b e y o n d o n e’s c o n t r o l ).
‘J o h r e i ’ literally m e a n s “ p u r i f i c a t i o n o f , s the p o i r i a t p ” p r o a c ma h y al s o p r o v i d e a n
a l t e r n a t i o v r e a d d i t i o n a l p e r s p e c t i n v lif e e even o ts wi th th e con cep t o f s p i r i t u a [ Seaward l i t y ,
2 0 0 0 ] . E x p e r i e n c e o f J o h r e i l i f-c s on a tai s ne ed ti me wh en on e can q u i e t l y, m i n d f u ll y an d kin d l y
con cen trat e u p o n t h e r e c i p i e n t ’ s b e n e f i t, a s w e l l a s h i , s s / i h n e c r e t o h w e n J o h r e i p r a c t i c e i s
b as ed u p o n t h e c o n c e p t t o h n a e t c a “ n h e a l o n e s e l f b y h e a l i n g ” o [ t N h a e i r t s o , 2 0 0 3 . ]
H e n c e , J o h r e i d i f f e r s f r o m s e -h l f y p n o s i s i n a i t n l y h i a n t p a , i alth r s i o ut gh i s p r a c
s e l f-J oh rei an d d is tan t J oh rei t e c h n i q u s e c a n b e p r o v i , d a e n d i n f a c t, w e r e p r o v i d e d a t th e en d
o f t r a i n i n g s e i s n s i t o n h e c u r r e . n I t n s a t d d u i d y t i o n , t e a c h i n g a p p r e c i n a d t i i n g o s n an d o f s u r r o u
h u m a n r e l a t i o s n (n s h amel i p y ‘Spiritua l C o s’) r d is g i v e n a s a o n e o f m a j o r fi ve p r i n c i p s l to e
p r a c t i se J o h r e i [A p p e n d -2ii]. i x Th es A e c on cep ts m a y b e c ollecti vel y a b l e i t n o c r e a s e a s en s e of
r e c e i v i n g s u p p o r t (m a n a g e a b i l ) i a t n d y to en h an ce th e m e a n i n gf u l n e s, b o t h o f w h i c h a n
p r o m o t e c op in g ability [1 . 2 . 3 ].
. 2
P h . D . a t U n i v e r s i t y o f L o n d o n - 4 1 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
P o s s i b l l e t a e r a t s in i o the n neu ra l pa rt o f t h e n e t w o r k
H y p n o s i s , b y d e f i n i t i o n , c o m p t r h i r e s e s i n t e -lin r ked p r oces s es [ S t e w a r t , 2 0 0 5 : ]
1 . Fo c u s e d a t t e n , t i o n
2 . In d u ct i on of a h yp n ot i c state, a n d
3 . Re c e p t i v en e s s t o s u g g e s . t i o n
P os itive emi s s i on top o grap h y (P ET) s tu d ies h ave imp lied th at th es e p roces s es o f h yp n os is
a r e n o t p r o c e s s o f s i m p l y f o l l o w i n g i n s t r u c t i o n s b u t t h e y i n v o e l a v ch an ge of p er cep ti on in th e
b r a i , n s u c h a s in vi s u al p ercep ti on [ K o s s l y n e t a l . , 2 0 0 0 a ] nd in p a i n s e n s a t [ i Fa o n ym on vi ll e et
a l . , 2 0 0 0 ]. P a r t i c u l a r l y in i p ercep n p a ti on , it w a s s u g g e s t e d t h a t is t h a e s r t e r o n r g e l a t i o n s h i p
b etween th e p s yc h o l o g i c a l s t a te o f m i a n d n e u r o l o g i c a l r e s p t o n s p e a i n s t i m , u i.e. l u s a p ai n
s timu lu s was s h own to cau s e d ifferen t n eu rolo gical res p on s es w h e t h e r n a in creas e or a d ecreas e
i n b l , o d o e d p e n d f i g n l u p o n w t h e s t a t e o f m i n ‘h d y p i n o t i h c e s t ’ a [Mon t e tg ome r y et al .,
2 0 0 0 ; P a t t e r s o n & J e n s e n , 2 0 0 . 3 ] H e n c e, i t w a s s u g g e s t e d t h a t self-h yp n os is ma y d irectl y b e
a b l e t o a l t e r t h ap e p rais p r i al m at a tr h y e u n c o n s c i o u s l e v e l as well as at th e c o n s c i o u s l e v e l.
O n t h e t h o e r h a n d , f e w s t u d i e s h a v e th e i pn hv ys e s iol t oi gi g cal a t p e r d o c e s se s as s oci ated
w i t h a J o h r e i s e . s s wi o T o pn rel i mi n ar y s t u d i e s h ave d emon s trated th at exp erien ced p ractition ers
w e r e s h o w n t o i n c r e a s e t h e h a p o w a e v r e s, o w f h i a c l h p i n d i s c a t a e n e x p e r i e n c e o f r e , l a x a t i o n
d u r i n g t h e J o h r e i [Dwived s e s s i o et n al . i n p r e p a r a ]. t Single-b i o n l i n d e d s ies t u c d o m p a r ing a
J o h r e i s e s s i ( recei o n ver was s it ti n g wi th e yes cl os ed , s ep arated b y a cu rtain f r the o m p ract it ion er ,
a n d g iv e n J o h r e i f r o m b e h i mock n d ) s a e n s d s i o (th n e s ame s et ti n g wi th th e s ame ar m
mo vemen ts of th e s am e p ractition e r b u t with n o in ten tion b y t h pe ractiti on er to p r act is e J oh rei)
h a s d e m o n s t r a t h t a t e d s i m u l t a n e o u s l y r e c o r d e d b r a i n w a v e s f r o m b o t h n d p r e a c e t i v e t r i o n e r a
e x h i b i t se ign d ifi can tl y in cre as ed level s of ‘m u t u a l i n f o r m ’ a in t i t o h n alp e h a wave b an d (an
exp erien ce o f rel axat i on ) i n t h e J o h r e i , bs ue t s ns ot i in o n th e moc k c on d it ion [Dwi ved i et al. in
p r e p a r a t ]. i T o n h i s i n d i c a t e s a y in t creas h e a their t l e v t e l s h of e rela xation J o . h r e i s e s s
C o n s e q u e n t , l i t y w a s s u g g e s t e d t h a t th e p r a c t i c o e f J o h r e i m a y d i r e c t l y b e a b l e t ed o ur ce s tres s
l e v e l s.
I n s u m m a r y , t h w e po s ych ol ogi cal trai n i n g in terven tion s , self-h yp n os is an d J oh rei , were
i n t e n d e d t o p r o v i d u e b j e s c t s w i t h t e c h n i q u e s t o a l t e h r pe erc ep ti on of s tres s ors , to en h an ce
cop in g s ki ll s an d to p r ovi d e p r ofou n d rel axation [T e x t b o x ], a 4 n d t h e r e b t y o r e d u ce t h e e f f e c t s
o f s t r e s s u p o n t h -n e e u p r s o-e y c n h d o c r i n -im o mu n e n et wor k.
P h . D . a t U n i v e r s i t y o f L o n d o n - 4 2 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
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P u b l i s h e d f i n d i n g s r e g a r d i n g -as s t r se oc s s iat ed ch an ges are c omp lex an d d ifficu lt to
s u mmari ze b ecau s e o f t h e h u g e v a r i e t y o f s t r e s , s b o i r s o l o g i c a l m a r k e , r tim s , e p oi a n nd ts at
wh ich ch an ges ar e o b s e r v e d o r i n v e s t h t a i t g h a a t v e d b e e n u s e d i n t h e s e . s t Th u d is i e lat s ter d i f f e r e n c e i n p u b l i s h ed s t u d i e s i s p a r t i c u la r l y i m p o r t a n t w i t h r e g a r d t o t h e c u r r e n t p r o ect. j It is n e c e s s a r y, th e r e f o r , e t o b e ve r y s p eci fi c r egard in g th e timin g o f c h a n g e s i n s t r e s s r s e s that p o n s e
w i l l b e m e a . s u r e d
1 . 2 . 4 . C 1 h r o n o l o g i c a l d e f i o n f i s t i r e o s n s r e s p o n s e
T h e ch ron ol o gi cal d e fi n it ion a n d d i s t i n c o t f i s t o r n e s s r e s p o n s e s a r e a m b i ou g u s an d h ave
v a r ied f r o m s t u d y t , o e v s e t n u d t y h o u Han g h s Sel ye in trod u ced a c on cep t t h a t d e f i th n ree e d
p h as es of s t r e s s r e s p o n s e s a s t h e n a m e o th f e ‘g e n e r a l a d a p t a t i o n s y n d ’ r [ o S m e l e y e , 1 9 7 5 b ]:
1 . Ala r m s ta g e: t r i g g e r d i u n r g i n g w h i c h m a r s h a lled r e s o u r c e s a r e o ; r g a n i s e d
2 . Res is ta n ce s tag e: ad a p t a t i d o u n r i n g w h i c h r e s i s t a n c e t o a l a r m r i s e s a b o v e n o r m a ; l
a n d
3 . Ex h a u s t i o n s t a g e : wh en ad ap tat ion en ergy is u s ed u p .
R ecen tl y, it ha s b een d e m o n s t r a t e d b y u s i n a g m e t a-a n a l y si s s t r a t h t a e t g y S e l y ’s e t h ree
c a t e g o ri e s o f s t r e s s r e s ma p o y n hs ae ve c o u n t e r p ar t s w i t h i n t , an h d e ma y i m m u n e s y s t
r e p r e s e n t th ree d ifferen t i mmu n olo gical m o d i f i c a t s i [ S o e n g e r s t r o m & M i l l e r , 2 0 0 : 4 ]
1 . Up-re gu l at i on of i n n at e i m mu n it y an d s up p res s ion of ad ap tive im mu n it y b y s h o r t -
lasting ( s e c o n d s t o m i n u t e s ) s t r e s ; s
2 . Cy t o k i n e s h i f t f r o m T h [ E . l 1 e n k t o o v & T h C . h 2 r o u s o s , 1 9 9 9 witho ] u t con s is ten t
ch an ges in cel lu lar immu n it y b y t e m p o r a l ( h o u r s t o d a y s s ) t r e s s; a n d
3 . Gl o b a l i m m -s u u n p o p r e s s i o n l b o y n -l g a s t g i (wee n ks , m on th s to years ) s t r e s s.

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
In c o n t r a s t , t h e r e i s a w e l l-u s e d d i c h o t o m i s e d c h r o n o l o g i c a l d i s t i n c t i o n , i n i . . s acu t e r e te s s
an d s u s tain ed or ch ron ic s tres s . In te rms of th e g e n e r a l a d a p t a t i o n s y n d , r o cu a m te, e m omen tar y
o r s h o r t l a s t i n g s t r e fs orth s ( acu h e n tc e s t res s ) is d efi n ed con cep tu all y as th e s tres s th at falls in
th e p eri od fr om th e a l a r m s t a to g e t h r e e s i s t a n c e s t . a Su g e s tai n ed or ch ron ic s t res s (s u s tain ed
s t r e s s t h ) r e e s i s i t a s n c e s f t to a r g e t o h e m x h a u s t i o n s t . a g e
C o n s i d e r i n t g h s e l e e -w p a k e c yc l e a s a b i o l o g i c a ll y f u n d a m e n t a l , p e a r c u i t o e d o r s u s t a i n e d
s t r e s s i n t h i s t h e is s i s de f i ed n on th e b as is of t h i s c y c . l T e h a t i s cu , te a s tres s is d efi n ed as s tres s
th at h as it s effect s w i t h i n o n e d a y o r , i n o t h e r w o r d s , a s i n g l e c i r on c a tras d i a t, n r h y t h m . I n c
s u s tain ed s tres s is d efi n ed as s tres s th at has its effects f o r m o r e t h a n , o n e i . . od ver e a y mo re th an
on e circad ian rh yt h m. Th is can b e c o n s t r u e d a s “Su s tai n ed s tres s al ters ci rcad ian p attern s of th e
p s y c h o-n e u r o-e n d o c r i n -i o m m u n e n e t w o rk.”
D u e t th o e n a t u r e o f p s y c h o l o g i c a l in i n wh t e ich r v te rai n t n i n g o n a n d p r a c t i c e o c c u r ove r
a p r o t r a c t e d p e r i o d d ( a y s , w e e k s a n d m o n t h s ), th e effects of s u s tain ed s tres s u p on med iators in
t h e p s y c -n h e o u r o-e n d o c r i n -i o m mu n e n et wor k are th e cen tral f ocu s o f in teres t i n t h i s t h e . s Th i s e
wor kin g h yp ot h es i s i n t h e p roject is that su s tain ed s tres s dis tu rbs p s ych olo gical b al an ce with
c o n s e q u e n t i a l i n f l , a u n d e t n h e c d e t a s i l e d u c h p a n g o e b s n s e r v t e u nd dh er e i m m u n e
s u s tain ed s tres s s u pp ort in g th is wor kin g h yp oth es is a r e e x p l ained b e l o w i n j u c n o c t i o n w the i t h
s t r e s s r e s p o n s e in s th e p s y c h o-n e u r o-e n d o c r i n -i o m m u n e n e t w . o r k
1 .2 .4 . 2 A c u t e s t r e s r s e s p o n s e s t i h e n n e u -e r n o d o c r i n -i o m m u n e n e t w o r k
In th e p s y c h o-n eu ral p a rt o f th e p s y c h o-n e u r o-e n d o c r i n -im o mu n e n et work , th e p r i mar y
a p p r a i s a l o f a sc tres u t e s , p art i cu larl y rew ard an d f e a r r e a c t i o , n a s r e b i-d i r e c t i o n a l l g y u l r a e t e d v i a
n e u r o-h orm on al s ecret i on s [ C h a r n e y , 2 0 0 4 ]. In th e n erv ou s s ys te m, acu te s tres s is s h own to
a c t i v a t e t h e r s e y c r e n t o e u r o n s t h r o u g -er h gic in a n ervat m i in on e s ir n tg h e i c a n d G A B A
au ton omi c n er vou s s ys te m [ C o l e & S a w c h e n k o , 2 0 0 2 . ] This a m i n e r g i c p a t ha h s w a b y e e n
r e p o r t e d p r t o j o e c t d i r e c t l o y t h e C R F n e u r o n s i n t h e y H P o f A , t h o b e t h u e t r n eu m ral a n
n e t w o r k s utilise n e u r a l s yn a p t i c s i g n a l s v ia a n i n h i -e b rgic i nt et wo or r k y [ d e K G l A o e B t , A 2 0 0 3 ]
i n c l u d i n eu g ron n s in th e SAM. Fo r e x a m p l e , th e e x c i t a t o r y i n p u t s f r o m -c or l tical i m b regi i c on s
m o d u l a t e -e r t g i c h i e n t e r-n G eu A r on B A al n et work [C ol e & Sawch en ko , 2 0 0 2 ; Her man et al.,
2 0 0 2 ] . T h i s a s h b e e n s u gges ted to p r o v i e d a s t r e s s o r a s p e c i f i c -ch n e emi u r o cal s ig n at u re to th e
s ecretor y n eu ron s [ P a c a k & P a l k o v i t s , 2 0 0 .
1 ]
P h . D . a t U n i v e r s i t y o f L o n d o n - 4 4 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
In th e n e u r o-e n d o c r i n e p a r t o f t h , e i t n e w t a w r s o e r c k e n t d l i s y c o v e re d that th ere ar e b oth
m i n e r a l o c o r t i c o i d r e c e p t o r s ( M C R s ) a n d g l u c o c o r t i c o i d r e c e p t o r s ( G C in R th s ) e b rai n [d e Kl oet ,
2 0 0 0 ] as wel l as i n t h e en d ocrin e or gan s . H e n c e , d e Kloet [2 0 0 3] h a s h yp o t h e s i s e d t h a t t h e
M C R s a n d G C R s h a v e i n t -c e r omp lemen t ar y e ffect s a gai n s t s tres s res p on s es in th e cen tral
n e r v o u s s y s t e m s. S p e c i f i c a l l y , i t w a s h y p o t h e s i z e d t h a th t e ( 1 s) ymp at h et ic n eu ron s an d MC R s
r e s p o n d t o a c u t e s t ; r e a s n s d t h e n t h a t ( 2 ) s o o n aft e r th is res p on s e, th e p aras ymp ath etic n eu ron s
a n d G C R s f a c i l : i t a t e
1 . Re c o v e r y o f s t r e -i s s n d u c e d a c u t e i m m u n e r e s p o n ; s e s
2 . C o n t r o l o f e n e r g y in th m e e n t d o a c r i b n e o s ys l t e i m ; an s d m
3 . P r o m o t i o n o f i n f o r m a t i o n s t o t r h a be rain g e [ i d n e K l o e t , 2 0 0 3 . ]
I n t h ie mmu n e s ys tem , it ha s b e e n e l u c i d a t via e d m e t a-a n a l y s i s th at acu te s tres s in creas es
t h e n u m b -c e l r l s o i f n t h N e K b l o o d Ns K t r c yt e a ot m oxi a c n act d ivi t y, b u t th a t th er e is n o
con s is ten t effect u p o n t h e n u m -c b e r l l o -c s f ells o T [ S r e g e r B s t r o m & M i l l e r , 2 0 0 . 4 ] In a d d i t , i o n
it ha s b een s h o w n t h a t t h e a c u t e s -i t r n e d s s u c e d i n c r e a s e d N K c y t o t o , x mi eas c ua red c t i in v i t y
p e r i p h e r a l b l o o d m o n o n u c l e a r c e l l s ( P B M C , was s ) n ot d u e to an in creas e in t h e p e r-N K -cell
c y t o t o x i c a c t i v i t y s b u t d w u a e t o a n i n c r -cells e a s in e P BMC i s n [S ege p rs te ro r m c e n t a g e s
& M i l l e r , 2 0 0 4 . ] F u r t h e rm o r e, i n t h e i n t e r a c t i o n b e t w e e n t h e e n d o c r i n e a n d i m m u , n e s y s t e m s
th e acu te s t r e s s-i n d u ced ch an ges in immu n e cell d is trib u ti on were s h own to b e a s s o c i a t d e with
th e exp res s ion of th e GC R s in mice [ D h a b h a r e t a l . , 1 9 9 . 6 ] D i u r n a l es c h in a n ad g ren al s teroi d s
w e r e kn own to b e a s s o c i a t d e w i t h c h a n g e s o f te l de is u tri k o bc uy ti on , i .e. th e d iu rn al p eak in
glu coco rt i coi d (co rt i s ol ) l evels c oin cid ed with a d iu rn al trou gh in the n u mb er of p e rip h eral
b lood l ymp h oc yt e an d vi ce ve rs a [ M c E w e n e t a l . , 1 9 9 . 7 ]
Acu te s tres s a c t i n g t h r o t u g h e S A M a n d H P A a x e s o f -e n t d o h c e r i n e n -im u o r mu o n e
n etwork ha s b een s h ow n t o h a v inter-c e o m p l e m e n t a r y e f f e c t s a g a i n s t s t r e s s r e s , p i.e. o n s t e s o
p rom ot e o r t o s u p p r e s s i n f l a m t m o r a y r e a c t i o n [ s C h r o u s o s , 1 9 9 5 ; H u e t h e r , 1 9 9 : 6 ]
1 . Pr o m o t ing i n fl a mmat i on as th e alar m or ‘f i g h t o r flig h t ’ r e s p o n s e [C an n on , 1 91 4 ;
G o l i g o r s k y , 2 0 0 1 ]: t h e S A M a x i s i s s t i m u l a t e d t o p r o d u c e s wh c a t ich e c h o l a m i n e
a c t a s im mu n ol ogi cal ‘a l a r m s i g n a ls’ b y p r o m o t i n g s e c r e t -in i o flam n o mat f op r y o
c yto kin es [ E l e n k o v e t a l . , 2 0 0 0 b ] y m a i n l y s t i m on u l oc a t yt e es d [S trau b , M a ye r e t
a l . , 2 0 0 0 ]; a n d
2 . Su p p r e s si n g in fl ammat i on a s a r e s p o n s t e o t h e a l a r m ( r t e h a e c t r i e s o i n s t a s n t c a e g e
in the g e n e r a l a d a p t a t i o n s y n d r t h o e m o e r y ): ac u t e s t r e s is s kn own t o in creas e th e
P h . D . a t U n i v e r s i t y o f L o n d o n - 4 5 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
l e v e l s o f c o r t i s o l [ R o h l e d e r e t a l . , 2 0 0 2 w ] h i c h c a n c o u n t e ra c t th e al arm s ign al an d
s u p p r e s s a ct ivat ion o f th e i mmu n e s ys tem [ M c E w e n e t a l . , 1 9 9 . 7 ]
H i s t o r i c , a t l h l e y c o n c e p t o f t h i s c o u n t e r a c t i n g m e c h a n -i i mmu s m ni e n t h e e n d o c r i n o
p a t h w a y i t n h e a c u t e s t r e s r s e s p o n s e w a s o r i g i n a p rop l l os y ed b y B e s e d o v s k y & S o r k in [1 9 7 7 ] . It
w a s t h e pn arap h ras ed b y M u n c k e t a l . [ 1 9 8 , 4 ] w h o h y p o t h e s th i at s e th d e s t r e s s-i n d u ced in creas e
i n c o r t i s o l l e s e v n e o l t s p r o d t e o c t a g a i n s t t h e s o u r c e o f s t r e s s , i t b s u e t l f r a t h e r a g a i n s t t h e b o s d y ’
n o r m a l r e s p o n s e s t o s t . r Th e s s is p roces s was s u gges ted to p r e v e n t t h o s t e r e s s r es p on s es from
exces s ive ov ers h oot in g p roces s es th reate n in g h omeos tas is [ M u n c k e t a l . , 1 9 8 . 4 ]
Al t h o u g h t h e w h o l e p i c t u r e o f t h e m e c h a n i s m o f t h i s c o r t i s o -in l d u ced s u p p res s ive immu n e res p on s e is yet to b e in ves ti gated [ S a p o l s k y e t a l . , 2 0 0 , 0 ] ortis c ol h as b een con s id ered
a s a m a i s n t r e s s h o rm on e wh ich can s u p p r e s s t h immu e n e res p on s e b y a f f e c t ing t a r g e t s m a i n ly
t h r o u g h i t s e p r t o e r c (G C R s ) . Th is is con s id ered t o o c c u r p r i m a inhibiting r i l y b y the N F B’s
gen omi c f u n c t i o n s t o p r o m -s o pt ecif e in c o i n fl amm at ion an d to in h ib it a p o p t osis [Ka rin & Lin ,
2 0 0 2 ] . In c o n t r a s t t o c o r t i s o l , a n o t h e r a d r e n a l h o r m o n e i n t h e HP A a x s i , d eh yd r oe p ian d ros teron e
( D H E ; A an d it s s u lp h at e D H E A -S), h as comp licated ef fects . D HE A ha s b e e n rep or ted to s t i m u l a t e T h . 1 c y t o ( k -2 i I n L e t c . ) p r od u ct ion [C leri ci et al., 1 9 9 7 ; Cu tolo et al. , 2 0 0 0 ; Loria,
2 0 0 2 ] a n d t o b e h a v e a s a n a n t a g o n i s t t o c o r t i s o l in th is Th .1 / Th .2 re gu lat ion [ Wo l f &
K i r s c h b a u m , 1 9 9 9 ]. D H , hE owev A er, h a s al s o b een s h own to h ave a s imila r an d /o r s y n e r g i s t i c
e f f e c t w it h c ort is ol , i .e . inhibiting t h e N F B a c t i v a t i o n s u p a p n r d e s si n g p r o-i n fl am mat o r y
c yto kin es [ S t r a u b , S c h o l m e r i c h e t a l . , 2 0 . 0 0 ]
C ollecti vel y, it ha s b e e n s u gges ted th at a d ren al h ormon es (co rtis ol in p articu lar an d
comb in ed with D H E A/ -S ) p l a y a n i m p o r t a n t r o l e i -i n m t m h u e n e e n i d n o t c r e r i a n with c o t i o n
regard t o acu te s t r e s s r e s p o n s in e th e p s y c h o-n e u r o-e n d o c r i n -im o mu n e n et work .
1 . 2 . 4 . Su 3 s tai n ed s tres s a n d c h a n g e s th i e n p s y c h o-n e u r o-e n d o c r i n -i o m m u n e n e t w o r k
S u s t a i n e d s t r e h s s a s b e e n d e m o n s t r a t e d to in d u ce vari ou s c h a n g e s th i n e p s y c h o-n e u r o-
e n d o c r i n -i o m m u n e n e t w . o In r k t h e n e -i u r m o u n e b i-d irect ion al in teracti on [ La wr en ce & Ki m,
2 0 0 0 ] , t h e b -b l r o a o d i -b n ar rier p e r m e a b i l i a w t s y f ou n d to b e in creas ed u n d er Gu lf War s t res s
[ F r e e d m a n e t a l . , 1 9 9 . 6 ] It has al s o b een s h own th at i n h i b i t -e o r r g i y c n e G r A v B o u A s a c t i v i t y
was a t t e n u a t d e u nd er s u s t a i n e d s t r e [ s V s e r k u y l e t a l . , 2 0 0 . 4 ] T ese h f i n d i n g im s p l y t h a t t h se tres s
r e s p o n s e s i n t h e n e u r a l l e v e l u n d e r s tres s u s can t a i bn e more h yp e ractive a n d t h e b n e c o m e
d i f f i c u l t t o s w i t c h , o w f f h i c h m a y r e s u l t i n m a i n t ing a i n a v i c i o u s c y c o l f e s t r e s s r e s p o n .
s e s
P h . D . a t U n i v e r s i t y o f L o n d o n - 4 6 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
I n t h e i m m u n e s y s t e m u s, tain s ed s tres s h as b een d emon s trated to alter tis s u e s p ecific
d i s t r i b u t i o n o f l y m p h s o u c -p b y op t e u lat io n s i n v i [ v S o u d o e t a l . , 1 9 9 . 7 S ] p e c i f i a c l l y , erip p h eral
N K -cell l e v e l s h a v e b e e sn h own to d ecre as e u n d er s u s tain ed s tres s [Bor ella et al ., 1 9 99 ;
G r u z el i e r , S m i t h e t a l . , -Sa 2 0 0 ku 1 ; rai I et n o al u ., e 2 0 0 0 ; Maes et al., 1 9 92 ; Segers trom & Mille r,
2 0 0 4 ] . In c on t ras t , t h e e ffect s of s u s tain ed s tres s u p on in vivo d i strib u tion of l ymp h oc ytes ar e
n o t c l e a r-cu t an d are in con s is ten t in t h e l i t e r a , t u i r . e e . s i n o v m e e s t i g a t o r s r e p o r t in c reas es an d
oth ers rep o rt d ecreas es in th e s u b-p o p u l a t i o n c o u n ts ( e . g . h e l p e r T-l y m p h o c y t s e [d e Gu ch t et al .,
1 9 9 9 ; M a e s , V a n B o c k s t a e l e e t a l . , 1 9 an 9 d 9 ] c yt ot o xi c T-l y m p h o c y t s e [ Gru zel ie r, Smi th et al . ,
2 0 0 1 ; M a e s , L i n e t a l . , 1 9 ). 9 Non 9 ] et h el es s , in fu n ct ion al i n v i meas t r o u res of th e i mmu n e
s ys te m, su s tai n ed s tres s has b e e n s h o w n to s u p p res s cellu lar i m m u n e r s e p o n s es [B au er et al .,
2 0 0 1 ; B o n n e a u e t a l . , 1 9 9 8 ; D h a b h a r & M c E w e n , 1 9 9 7 ; K o h , 1 9 9 8 ; S e g e r s t r o m & M i l l . e r , 2 0 0 4 ]
H e n c e , s u s t a i n e d s t re s s h as b een b elieved to cau s e a d etri men tal ef fect u p on im mu n e cells in
v i v o r e s u l t i n g i n a n i d n c s r u e s a s c e p t i b i l mali i t gn y an t co y [ G a r s s e n , 2 0 0 4 ] a n d i n f e c n t [C i oh o en
& He r b e r t , 1 9 9 6 ; Ki e c o l t-G l a s e r & G l a s e r , 1 9 9 . 9 ]
N o t a bl y, t h e r e w a s a r e p o r t [ B o n n e a u e t a l . , 1 9 9 8 ] d e m o n s t r a t i h a n t g a d r e n a l e c in t o m y
m i c e p r e v e n t e d t h e s u p p r e s s iv e e f f e c t o f s u s t a i n e d s t r e s u s p o n th e a c u t e s t r e -in s s du ced immu n e
activation (meas u red b y i n v i c t y r t o t o x i c a c t i v i c y t o y k i a n e n d p r o d u c t i o n . ) H e n c e , ad ren al
h orm on es were s u g ges ted to p la y an e s s e n t i a l r o l e i n t h e o-s i u p m p m r e u s n s i v e e f f e c t of
s u s tain ed s t res s . Fu r t h e r , t h e r e a r e c o n t r a d i c t i v e c l i n i c a l f i n d i n g s w i t h r e g a r d to c o rtis ol le vels
u n d er s u st ai n ed s t res s , i .e. cortis ol le vels are h igh in p atien ts with th e p os t trau matic s t res s
d i s o r d e r ( P T S D ) a (k n d n o w d n e p r a e s s a i ) o in h n p ati , y en p to s a wi c n th d o r l t o i w s o l i s m
s o m a t o f o r m d i s o r d e ( r s c h r o n i c f a t i g u e s y n d r o m al e , gia, f bi u rn b r ou o m t sy yn d ro me et c.) [ Heim
e t a l . , 2 0 0 . 0 Th ] ere h a v e b e e n two in terl i n ked h yp ot h es es r e g a r d i th n g e mech an is ms w h i c h
c o n t r i b u t e t o s u p p r e s s c e l l u l a r i m m u e n s e p o r n s e s u n d e r s u s t a i n e d s t r [T e s e s x t b o x ]: 5
1 . Su s t a i e d n exp os u re to h igh l e v e l s of c o r t i s o l ; a n d
2 . At t e n u a t e d r e s p o n s e s c a u s e bd y h a b i t ation u t o r e p e t i t i v e s t i m u la t i . o n
Th e p r i m a r m y e c h a n i s m o f f t i r h s e t h y p o t h is, e s s u s t a i n e x d p o s u r e t o h i g h l e v e ls o f
c o r t i s o l , i s t h a t t h e s t r e s s r e a c t i o n i n t h e H P A a x i s i f s t c a o y p s i n a g c t w i i v t e h s t lls r e us ns d er f a
th e s u s t ai n ed s t res s , t h erefore t a r g ets are exp os ed to el evated le vels o f c o r t i s o l f or a p rolon g ed
time [ d e K l o e t , 2 0 0 3 . ] Th is ma y b e a s s o c i a t d e with mu lt ip le p os it ive feed b ack l oop s in th e HP A
axis [ G o l d e t a l . , 2 0 0 , 2 t ] h e n t h i s s u s t a i n e d h i g h l e v e l s ex acerb o f c at o e r t ht e i is mb o l al an m ce a y
o f i n t e r a c t i o n s w i t h i -n n e u t r h o-e e n d p o s c y r c i h o n -i o m m u n e n e t w [ o d r e k K l o e t , 2 0 0 3 , ] in clu d in g
P h . D . a t U n i v e r s i t y o f L o n d o n - 4 7 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
l o s s o f n e u r on s i n t h e h i p p o a c m p u s [ S a p o l s k y , 2 0 0 0 ]. Fu r t h e r , it i s w e l l-kn o wn th at mos t
p atien ts wi th d ep res s ion h ave ch an ged cir cad ian p a t t e s r in n t h e n e t w o r k , p a r t i c o c r u t i l s o a l r l y i n
levels , i.e . el e vat ed tr ou gh an d flatten ed p e a k l e v e l s w i t h a n r a r n r g o e w e o d f f l u c t u a t i o n
[ G o l d s b y e l t . , a 2 0 0 2 ; W e b e r e t a l . , 2 ; 0 as 0 0 ] w e l l a evid s en ce of s y m p a t h e t i h c y p e r a c t i v i t y
[ B e l a n o f f e t a l . , 2 0 0 2 ; C h r o u s o s & G o l d , 1 9 9 2 ; Go d l & C h rou s os , 1 9 9 9 ; Hol s b oe r, 2 0 01 ;
S c h a t z b e r g e t a l . , 1 9 8 . 5 F ] u r t h e r m o r e , g r o w i n g e v i d e n uc gges e s ts th at th e med iat o rs of th e S AM
a n d H P A a x s e are r e p e a t e d l y e l e und v a t er e sd u s tai n ed s tres s and often fail t o s h u t off p romp tl y
b e f o r e xp eri en ci n g an ot h er r e p etitive ch allen ge b y a s t res s or [ M c E w e n e t a l . , 1 9 9 . 7 ]
Th e lat er m e c h a , a n t i t e s n u a m t r e d s p o n s e c a u s e d b y a h b i t u a t [ i Kirs o n ch b au m et a l .,
1 9 9 5 ; S c h o m m e r e t a l . , 2 0 0 , 3 is ] als o k n o w n a s a p r o g r e s s i v e d i m i n u tion o f t h e r e s p o n s e
again s t r e p e t i t i v e s t i m u l ation [ H e i m e t a l . , 2 0 0 . 0 Th ] e at ten u at ed res p on s e in h ormon al s ecretion
h a s b e e n o b s e r v e b o d t h i th n e ne u r a l l e v e l (a m y g d a l a) [ C a r t e r e t a l . , 2 0 0 an 4 ] d th e H P A a x i s
[ G a a b e t a l . , 2 0 0 2 ; J o h n & B u c k i n g h a m , 2 0 0 3 ; P a r i a n t e & M i l l e r as , 2 well 0 0 1 ] as th e c yt o ki n e
level [ G a ab e t a l . , 2 0 0 . 5 It ] ha s a l s b o e e n d e m o n s t r a t e d t h a t s u s t a i n e t d t s e n t u r a e t s e s t h a acu e te
s t r e s s re s p o n s es in th e en d ocrin e an d immu n e s ys te ms . A s a c o m m e n c i n g c o n d i t cu i o te n , s tres a s
i n c r e a s e g l u c o c o r t i c o i d s a n d a l t e r l y m p h o c y t e d i s d t s tream r i b u t o f i r at o n s . Th i n e t h e b l o o
g r e a t e s t c h a n g e s i sn e, glu t h e coc ort ic oi d level s an d a l t e r a t i o n o lf ymp h oc yt e d i s t r i b u , t were i o n
s e e n o n D a y 1 , b u t t h e r e a f t w e i r t h r e p e a t e d e x p o s u r e t o t h e s a m e a c u t , e th s e t cr he an s s ges
d ecreas ed an d reach ed th ei r lowes t at Da y 3 5 [ D h a b h a r & M c E w e n , 1 9 9 7 . ] A c c o r d i ln y, g it is
h y p o t h e s i s e d t h c a t c a u m u l a t e d n e g r e a p e t i t i v i e r v e s e p o n s e s f i n e b o e th d th e b SAM a c k s f r o m
a n d HP A a x e s r e s u l t in imp aired r eaction s in th eir h o r m o n e s e c r e s. t i o n
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Th es e ma y b e ab l e t o rep res en t th e d iffer en t s tages of th e s u s tain ed s tres s , i.e. th e r es i s tan t
a n d t h e e x h a u s t i s t o n a g e s i n t h e ’s S e gl en y e eral ad ap tat ion s yn d r ome . It s h ou ld b e n oted ,
h owever , th at th ere remai n s c o n f u s i o ab n ou t th e mech an is ms t h a t u n d e r l s i u s e t a i n e d s t r , e s s a n d
P h . D . a t U n i v e r s i t y o f L o n d o n - 4 8 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
wh eth er th es e ma y be b e s t t h o u g h t , o f as two c on s ecu ti ve s tages th at occu r a f t e r a n o t h e r, or as
t w o d i s t i n c t res p on s es th at occu r in p arall el. O t h e r f a c t o r s l i k e g d e i n f e t f e i r c e n s c ( e e.g. gen d er)
ma y a l s o c o n t r i b u te to th is con fu s ion , b u t rep orts s till remain in con s is ten t [ Lu n d b erg, 2 0 0 5 ;
S a u r o e t a l . , 2 0 0 . 3 N ] o n e t h e l e s s , t h e c e l l u l a r i m m u n e r e s p o n s e s a r e b e l i e v e d t o b e i
m a i n l y b y e i t h e r o r b o a t b oh ve m e c h a s n i n s t h m e p -n s y e c u h r o o-e n d o c r i n -i o m m u n e n e t w . o r k
H e n c e , t h i s p r o j e c t f e o d c u s o n t h e h yp o t h e s i s t h a t p s yc h o l o g i c a l i n t e r v e n t i o n c a n c o u n t e r a c t, o r
at leas t b u ffer, th e n e gat ive e f f e c t s o f s u s t a i n e d s t r e s s u p o -n n e u t r h o-e e n d p o s c y r c i h o n -im o mu n e
ne t w o r k , p a r t i th c u e l im a r mu l ny e s ys te m.
1.3 Ap p r o a c h t a k e n
T h i s t h e s i s i s b a s e e hd yp ot u p ho es n is t h at p s ych ol ogi cal in terven tion actin g th ro u gh th e
p s y c h o-n e u r o-e n d o c r i n -i o m m u n e n e t w o w r i k l l c o u n t e r a c d t e t r t i m h e n t a l e f f e c t o f s tres s on th e
i m m u n e sy s t .�In e v e m s t i g a t i o n w a s p e r b f y uo sr in m g e a d s e ri es o f i n v i an v o d i n v i st tud r o ies .�
Th e p s ych ol ogi cal i n t erv en t ion s u s ed to cou n teract s tres s were Self-h yp n os i s an d J oh rei,
b o t h o f w h i c h p r o v i d e t r a i n i n g a n d p r a c t i c e o f -h s e l f p s t r e s s m a n a g e m ne iq n ut es .� t e c h
U n i v e r s i t y s t u d e n t s f a c i n g e x a m i n a t i o n w e r e u s e d a s a n e x a m p l a e t i o m f -l e i m i t e d s t r f e u s l s
s i t u a t i o n , a n d th e p r i m a r y o u e t r e c N o -c K m e l e l p e m r c e n a t a s g e u s r a n d e N s K C A w l .� e v e l s
H I V-in fect ed p at ien ts were u s ed as an ex amp le of o n g o i n g d i s e a -a s s e s o c i a t e d s t r e f s u s l s itu at ion ,
an d t h e p r i m a r y o u t c o m e m e a s u r e s w C a D s 4 -c e T l l c t o u s n . uA mb n er of val id at ed
q u e s t i o n n a i r e s w a s u s e d t o d e m o n s t r a t e t h a t s e a x n a d m -g o i n o n i a n t g i o d n i s e a s b e o t in h du ce
s t r e s s, a n d t o e x p l o r e t h e e f f e c t s o f t h e en p tion s y c s h uo pl on o g si tres c a s l p ercep i n t te ion r v .
In ad d it ion , i n v i exp t r o eri men ts were p er for med to exp lo re th e d irect in flu en ce o f t h e
s tres s h orm on e, co rt is ol , on th e p erip h era l N K -c e l l s -l a y m n p d h o c T y t e s.
P h . D . a t U n i v e r s i t y o f L o n d o n - 4 9 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Chapter II
M a t e r i a l s a n d M e t h o d s
P h . D . a t U n i v e r s i t y o f L o n d o n - 5 0 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
C O N T E N T S O F C H A R P T E 2
M a t e r i a l s a n d M e t h o d s
2 . 1 P a r t i c i p a n t w s i t h r e g a r d s t o o u t c o m e s a n d m e a s u r e m e n t t i m e p o i n t s
2 . 1 . 1 S t u d e n t v o l u n t e e r s
2 . 1 . 2 P a t i e n t v o l u n t e e r s
2 . 1 . 3 C a s e m a t c h e d p a t i e n t s f r o m d a t a b a s e
2 . 1 . 4 L a b o r a t o r y v o l u n t e e r s
2 . 2 P s yc h o l o g i c a l in t e r v e n t i o n
2. 2 . 1 Self-h y p n o s i s t r a i n i n g
2 . 2 . 2 J o h r e i t r a i n i n g
2 . 2 . 3
M o c k i n t e r v e n ( t C i o n o t n r o l s f o r t h e p s y c h o l o g i c a l t r a i n i n g s )
2 . 3 S e l f-r e p o r t u e s q t i o n n a i r e s
2 . 3 . 1 S t r e s s p e r c e p t i o n
2 . 3 . 2 . 1 State an xi et y s c ore in th e State a n d T r n a x i e t y I n A v e n t o r y
2 .3 .2 .2 I m p a c t o f E v e n t S c a l e ( I E S )
2 .3 .2 .3 P e r c e i v e d S t r e s s S c a l e ( P S S )
2 .3 .2 P e r c e i v e d q u a l i t y o f l i f e
2 . 3 . 2 . 1 L o c u s o f C o n t r o l s c a l e ( L o C )
2 .3 .2 . 2 M e n t a l C o m p o n e n t S u m m a r y i n th e S -3 F 6 (M C S ) 64
2 .3 .2 . 3 P i t t s b u r g h e S p l Q e u a l i t y I n d e x ( P S Q I )
P h . D . a t U n i v e r s i t y o f L o n d o n - 5 1 - I m p e r i a l o C n o d l o n l e g e L
63
63
63
63
64
53
56
58
60
60
61
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P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
2 . 4 M at eri a ls an d met h od s i n v i t r o
2 . 4 . 1 M a t e r i a l s a n d e x p e r i m e n t k i t s
2 .4 .1. 1 C h e m i c a l s a n d r e a g e n t s
2 . 4 . 1 . 2 B i o l o g i c a l r e a g e n t s
2 . 4 . 1 . 3 F l u o r e s c e n t l y c o n j u g a t e d a n t i b o d i e s f o r f l o w c y t o m e t r y 65 a n a l y s e s
2 .4 . 1 . 4 C omme rci al l y av ai lab le lab orat or y kits fo r col ori metri c a n a l y s e s 66
2 . 4 . 2
E q u i p m e n t s u s e f d o r i n v i i t n r v o e s t i g a t i o n s
2 . 4 . 2 . 1 F l o w c y t o m e t r y
2 . 4 . 2 . 2 C o l o r i m e t e r 68
2 .4 .3 Met h od s i n v i t r o
2 . 4 . 3 1 P r e p a r a t i o n o f or cell t cu i lt us re s i n u v e i t r c o u 69 l t u r e m e d i
2 .4 .3 .2 NK c yt ot o xi c acti vit y m e a s u r e bd y f l o w c y t o m e t r y
2 .4 .3 .3 N K -cel l ch aract eris tics d u rin g N KC A as s a y m eas u red b y fl ow
c y t o m e t r y
2 . 4 . 3 . 4 P rol iferat ive res p on s e m e a s u r e bd y [ 3 H ] -t h y m i d i n e i n c o r p o r 74 a t i o n
2 .4 .3 .5 T-cel l ch ara ct eris tics afte r i n v i t i r n o c u b a t i o n m e a bs y u fl r ow e d
c y t o m e t r y
2 .5 S t a t i s t i c a l a n a l y s e s
P h . D . a t U n i v e r s i t y o f L o n d o n - 5 2 - I m p e r i a l o C n o d l o n l e g e L
64
65
66
70
73
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64
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P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
2.1 P a r t i c i p a n t s w i t h r e g a r d o s u t c t o o m e s and me asur e me nt ti me
p o i n t s
2 . 1 . 1 S t u d e n t v o l u n t e e r s
Un i v e r s i t y s t u d e n t s f a c i n g t h e a c a n d e p m eri i od c were e x a m recru i n a it t ed i t o in ves tigate
th e effect s of a time-l i m i t e d s u s t a i n e d s t r e s acad s ( emi c e x a inations m ) u p on th e p ercep ti on of
s t r e s s a n d a s s o c i a t e d c h a n g e s i n i m m u n o l o g i c a l p a , r a m e t p e r a s r t i -cell c u p ercen l a tage r l an y d N K
N K C A l e v e l . s T h e y w e r e r ite e c d r th u rou gh p os ters d is p la yed in Imp erial C ollege Lon d on an d
b y w o r d-o f -m ou t h con t act s u s in g s tu d en t res earch as s is tan t s (P s ych olo g y BS c s tu d en ts ). Eth ical
ap p roval was gran t ed f ro m t h e R ive rs id e R es earch Eth ics C om mittee an d all v olu n teers were
g i v e n d e ta i l e d i n f o r m a t i o n s h e e t s , i n t e r v i e w e d a n d n a s k i e n d f o t r o m cs e on i d sg en n t a for m [s ee
Ap p en d i x 1 ] . Al l s u b j ect s were as ked to f as t ove rn igh t b efo re g i ving a m orn in g b lo od s amp le
(b etween 8 :0 0 an d 9 :0 0 a.m . in o rd er to min imis e d iu rn al effects [ M c G l o n e e t a l . , 1 9 9 ), 1 an ] d
g i v e n a s i mp l e b reak fas t aft e r th eir b lo od collection . At th e en d of th e s tu d y, e ach p articip an t
r e c e i v e d £ 3 0 f o el r e xp t en r a s es v an d in con ven ien ce.
In t otal, 4 8 u n ivers it y s tu d en ts were rec ru ited p rior to their e x a m i n a t s. i Th o n e med i an age
was 2 1 yea rs an d the r a n g e w a -2 s 3 1 ye 9 ars wi th on e p art ici p an t of 3 7 years . Th er e were 2 6
m a l e s a n d 2 2 f e m a . l T e s h i r t y n i o n f e t h p e a r t i c i p a n t w s e r e m e d i c a l s t u d e n a t s I m p e r i a l C o l l e g e
(fr om f i r s t t o f i f t h y e a r : s p e f c i t f h e i c o u y r e w s a e r e s n o t r e c o r d e d ) a n d t h e r e m a in in g n in e
w e r e o n o t h e r U n i v e r s i t y o f L o n d o n c o u r s e s ( w s p a e s c n o i t f r i e c o r d i e n d f ). o r m a t i o n
T h e r e w e r e t w o e x a m i n a t i o n p e r i a o n d d, s f o r t h e E x a m a s s e s s m e n t p o i n t , s t were u d e n t s
a s s e s s e d w i t h in f i v e d a ys p r i o r to t h e i r e x a m i n a t i [ o F n i s g u r s e 3 a n ]. d C 4 o n t r o l ( -exa N o n m)
p e r i o d s f o r c o m p a -p r e riod i s were o n ch os w en i as t fol h l ows : e f or x s o a m e m s t u d e n t s (C oh ort
A) , i t w a s f o u r w e e k s a f t e r e x a m i n a , t an i o d n for s t h e r e m a i n d e r (C o h o r ) , t it was B f ou r wee ks
after recru it men t (w h i c h w a s f o u r t o e i g h t w e e k Ex s a b m e s f ). o r Se tu d en ts were fre e to with d raw
f r o m t h e s t u d y a t a n y t i m e w i t h o u t g i v i n g a n y s p e c i f i c r e a , s o n a s n a d total of 2 1 s t u d e ts n
w i t h d [ r F i e g u s w r e 3]. B l o o d s a m p l e s w e r e t a k e n a n d q u e s t i o n n a i r e at s th w e e r e c o m p l e t e d
recru it men t an d at th e Ex a m a n d N -exa o n m as s es s men t p oi n ts .
P h . D . a t U n i v e r s i t y o f L o n d o n - 5 3 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
R e c r u it m e n t �
(48)
W i t h d r e w ( 1 0 )
W i t h d r e w ( 1 ) W i t h d r e w ( 1 0 )
Fi gur e 3: N u m b e r s o f tudents s r e c r u i t e d a n d r e m in a t i he n si t ud n g y a t t he Exa m a nd Non-e x a m
a s s es s m en t t i m e p o i n ts . T h e n u m b e r o -out f d s tr ud o p e nt s is a ls o indic at e d.
Weeks from the Recruitment
1 2
Fi gur e 4: T iming of the Ex a m a n d n-e N o xam a s s es s me nt t i m e p o i n ts wit h r e sp e ct t o re cru it me nt f or
i n d i v i d u a l s t u d the e n t Cohorts s i n A and B
Bef ore co mb in in g C oh ort s A an d B to tes t th e h yp oth es es th at (1 ) acad emic e x a m i n a t i s o n
c a u s e s t r e s s in u n i v er s i t s t y u d e n t ; s an d ( 2 ) p s y c h o l o g i c a l i n t c e a r n v e r n e t d u i c so e tn res s effect s ,
comp arab il it y o f t h e t w o g r o x a u m p s a nd a N t o n-e x t a m h t e i m e E p o i n ts w a s ed bc y o n f i r m
s t a t i s t i c a l a n a l y cs oe mp s ari n g C o h o r t s A a [ n A d p p e n B d i x 6 : T s a b l -1 A e t -6 o ] . T h e A l e v e l f s o
th e P SS and t h e S t at e an xi et y s c ore of th e ST AI, l ymp h oc yte s u b s ets d is trib u tion an d NK
c ytot oxi c act i vi t y (N KC A) w ere c omp ar e d . Th e levels of th es e meas u res were n ot d ifferen t
b etween th e t w o c o h o r t at s t h e N -exa o n m time p o i n t s, s o th e two c o h o r t s were co m b in ed into a
s in gle gr ou p i n ord er t o e xamin e ch an ges in th e levels of t h es e meas u re men t s .
A t o t a l o f 2 7 s t u d e n t s w e r e s t u d i e d , b u t n o t a l l o f t h e p a r t i c i p a n t s p r o v i d e d c o
s ets . Some d at a were in comp lete b ecau s e of t e c h n i c al f a i l u r e e w a i n t a l h y s e t s an h d b ecau s e
s t u d e n t s d i d rn n uo t p to t pu rovi d e s amp l es or failed to co mp lete q u es tion n aires . C on s eq u en tly,
t h e n u m b e r s i n e a c h a n a l y t s i o s t e s t fi rs t h h e yp o t h e s i s t h a t acad emic e x a m i n a t i s cau o n s e s tres s
in u n i v e r s i s tu t dy en ts w e r e :
8
4
0
4 w e e k s 4-8 w e e ks
C o h o r t A
E x a m
E x a m s
[Co h or t A (21)]
Non-e x a m
[Co h or t B (26 ) ]
Non-e x a m
R e c r u i t m e n t R e c r u i t m e n t
1 2
8
4
0
C o h o r t B
E x a m
Non-e x a m
Non-e x a m
[ G r o u p A ( 1 1 ) ]
Exa ms
[ G r o u p B ( 1 6 ) ]
P h . D . a t U n i v e r s i t y o f L o n d o n - 5 4 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
P ercei ved s t res s s cal e (P S S ) an al ys is : 2 2 s t u d e n t s
State an xi et y s c ore an al ys i s : 2 5 s t u d e n t s
N K c yt o t o x i c a c t i v i t y a n a l ys i s : 2 1 s t u d e n t s
C D 4 a n d C -c D 8 e l T l s -cell a an n al d ys es : N K
2 6 s t u d e n t s
In ord er t o tes t th e s ec on d h yp oth es is th at p s y c h o l o g i c a l i n t e r c a v n e n r t e i d o u n c e s tr es s
e f f e c t s, th e s a m e 4 8 u n i v e r s i t y s t u d , e as n t ds es cri b ed a b o v e , w e r e e a c h r a n d o m l y a s s i g n e d t o
o n e o f t h r e e g r o u : p s
R e l a x a t i o n o n c t r o l g r o u p : e xp eri en ci n g m o c k n e u r -f o e e d b a c k s e s s i o n s,
Self-h y p n o s i s g r o u p : t a u g h t a n d p r a c t i s i n g S -h e yp l f n o s i s wi th i m a g e r y , o r
J o h r e i g r o u p : t a u g h t a n d p r a c t i s . i n g a n o v
F o r b o t h C o h o r t s A a , n train d in B g an d p ract ice of ei th er in terven tion c om men ced at
r e c r u i t m e n t a n d w a s e n c o u r a g e d t o c o n t i n ir u e x u a n m t i n l a t i t o n h s e , t h ef e r ore , f or C oh ort A,
train in g an d p ract ice las ted fou r w eeks an d , for C oh ort B , ei gh t to twel ve w eeks . F o r a n a l y s e , s
b o t h i n a t e i x o n a d m a t w a e r e c o m b i n e d [ F ]. i g u r e 5
B a s e l i n �e
(48)
T r a i n i n -s g e s s i o n
W i t h d r e w 1) ( 1
Fi gur e 5: T i m i n g o f t -ups r and a i d a n ta-c i o n l l g e c , t i o n f s e i o s o n l s l ( B o a s w e l and i n e Ex a ms a s s es s ment
points) and nu m b e r s o f tudent s s a t t he s e s s i s o n
Of 4 8 s t u d en ts recru i t ed , 1 1 with d rew fro m th e s tu d y. C o mp lete d atas ets were n ot
o b t a i n e d f o r t h e 3 7 s t u d e n t s r e m a i n i n g . H e n c e , t h e n u m b e r o f s u b j e lc ys t s is v a r i e d f o r e a c h
comp ari n g b et ween th e p s ych ol o gical in terven tion grou p s an d t h e R e l a x a t i o n c o n t : r o l g r o u p
PSS 3 2 s t u d e n t s
S t a t e a n x i e t y s c o r e i n t h e S T A I
N K c y t o t o x i c a c t i v i t y
Practice & follow-ups
4 w e e k s 4-8 w e e ks
Exa ms
(21)
3 5 s t u d e n t s
3 1 s t u d e n t s
L y m p h o c y t e s -p u b o p u l a t i -c o e n l l s a n 3 d 4 s t u N d K e n t s
E x a m s
(16)
P h . D . a t U n i v e r s i t y o f L o n d o n - 5 5 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
2 . 1 . 2 P a t i t e n v o l u n t e e r s
Af t e r a p p r o v a l f r o m t h e R i v -in e fected r s i p at d ie ne ts wh R o e s e a r c h
were n ot recei vi n g a n t i -r e t r o v i r a l t r e a t m e n t (treatmen t n a ï v e H I -p a V t i e n t s ) w ere re cru it ed to i n v e s t i g a t ( 1 e ) t h e e f f e c t -goin s o g f d i o s n e a s e ( H -i I n f V e c t n ) i uo p on s tres s p ercep ti on an d
a s s o c i a t e d c h a n g e s i n i m m u n o l o g i c a l p a r a m e t e r s, C D -c 4 e l l T c o u n t i s n p a r t i c u l ; a r an d (2 )
w h e t h e r p s y c h o l o g i c a l i n t e r c v a e n t r i e d o u n c s e t r e s s e f f e c . t T s h e cl in ical im mu n ol ogi cal data
w e r e o b t a i n e d f r o m t h e p a t i e n as t e at r te hc e o Cr hd el sd ea a t an a d b Wes t min s ter Ho s p ital.
A t o t a l -i n f o e c f t e d i 6 n 3 d i v i d H u I a l V s i n c l u d i n g t h r e e , f with e m a a l e med s ian a g e of 3 7
y e a r s (r a n g e -5 2 7 8 y e a r s) wh o w e r e r e g u l a r a t t e n d e e s t o t h ’s e c S l t i . n i c S t a t e p t h e n C ea h e l s
an d Wes t mi n s ter Hos p it al , w e r e recru ited b y a r e s e a r c h a s s t i a s n t , M r . B r y a n M . B e n n e t t , a n d
res earch n u rs es accord i n g t o th e in clu s ion criteria : (1 ) n o t r e c e i v i n g a n t i-ret ro viral t r e a t m e n t , ( 2 )
n o s y m p t o m r -i e n f g e c a t r i o d n i ( 3 a ) n md ore g th H an I 2V 0 0 cel ls p er L o f C -cells’ D 4 T in t h e i r p e r i p h e r a . l T h b e l o o -in d H fected I V p art ici p an ts were giv en d etailed in formati on s h eets an d
e a c h g a v e s i g n e d i n f o r m e d c o n s e n t. T h e y p a r t i c i p a t e d f o r m o r e t h a n f i v e , m o n t h s i n t h e s
d u rin g Au gu s t 2 0 0 3 t o Decemb er 2 0 0 4 .
F o r e t h s t u d i n y v e s t i g a t in g t h e e f f e c t s -g oin o f g d o i n s e a s e ( H -in I fecti V on ) u p on s tres s
p ercep ti on an d as s oci at ed ch an ges in d i s e a se p a r a m e t e r s, t h e r a t e o f -cell d e c o l u n i t n e i n C D 4
was cal cu lat ed b e t w e e n t h recru e it men t ti me p oi n t a n d f o u r m o n t h s l a t e as r the p ri mar y ou tc ome
m e a s u r e o f t h e . T h s e t u t d y i m i n g o f c l e i c k-u n i p c s a l w i c t h r e g a r d t o w o t h t e i m e p o i for n t s th e
p s yc h o l o g i c a l a s s e s s m e n t (t h e R ecru itme n t an d After 4 mon th s ) was as foll ows [ Fi gu re 6 ] :
- Recruitment
-
Ba s e l i n e
Fi gur e 6: T iming of t he m e as u r e m e nt c olle ct io n t ime p o i n t s (R e cr u i t m en t and Af t e r 4 m o n t h s ) a nd t he
one-m o n t h b l o c k s (Bas e line , T e r m o n e t o T e r m f o u r ) f o r c l i n i c a l r o u t i n e b l o o d c o l l e c t i o n s
Un f o r t u n a t , e n ot l y all of th e p at ien ts recr u ited h ad th eir C D4 T-cell c o u n t s meas u red a t
e a c h T e r m [T a b l e ]. 4
T e r m o n e
T e rm t w o T e rm t h r e e
4 m o n t h s
- After 4 months -
T e r m f o u r
P h . D . a t U n i v e r s i t y o f L o n d o n - 5 6 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
T able 4: Numb er a nd per c ent a ge of H I V-i n f ec t e d i n d i vi d u a ls who had CD4 T-ce l l counts ch e c k a t t he m o n t h l y t i e m r i e o d s p f r m o t h e Re c r u i t m e nt to four mont hs a ft er th e r e cr uit men t (T er m 4)
N u m b e r s o f p a t i e n t s ( T o t a l N = 6 3 )
V a l i d n u m b e r M i ss i n g
N P er ce n t N P er ce n t
T e r m 4 ( f o u r m o n t h s a f t e r t h e R e c r u i t m e n t t i m e p o i n t ) 23 36.5% 40 63.5%
T e r m 3 ( t h r e e m o n t h s a f t e r t h e R e c r u i t m e n t t i m e p o i n t ) 18 28.6% 45 71.4%
T e r m 2 ( t w o m o n t h s a f t e r t h e R e c r u i t m e n t t i m e p o i n t ) 19 30.2% 44 69.8%
T e r m 1 n e ( o m o n t h a f t e r t h e R e c r u i t m e n t t i m e p o i n t ) 14 22.2% 49 77.8%
B a s e l i n e ( 2 w e e k s b e f o r e a n d a f t e r t h e r e c r u i t m e n t ) 22 34.9% 41 65.1%
T h e r a t e o f d e c l i n e Ci D4 n T-c t h e l l c o u n ts ( C D 4 g r a d i e n t ) was th eref ore cal cu lat ed fro m
t h o s e i n d i v i d u a l s w h o h a sd t two a t me l e as a u remen ts mad e in th e as s es s men t p erio d . Of t h 6e 3
p a r t i c i nts p a r e c r u i , on t e l y d 3 8 p a t i ) h ad e sn u ffi t ci en s t d at a ( from 6 0 wh . ich 3 to % c alcu late th e
rate o f d ecl i n e i n t h e C D 4 T-cells d u rin g th e fou r mon th p lu s on e mon th (fi ve mon th s
a l t o g e t h e r ) t u s d y p e ri o d , a n d i t r h e d a t w a e r e u s ed to i n v e s t i g a th t e a s s o c i a t i o n b e st tres w e s e n
p e r c e p t i o n da is n eas d e p rogres s ion .
T h e s a m e 6 3 -in H I fe V cted i n d i v i d u a l s were r a n d o m l y a s s i g n e d t o o n e o f t h r e e g r o u p s :
C o n t r o l (wait-listed c o n t r o l: w a i t i n g f o r f o u r m o n th s b efore b ein g ran d oml y
a s s i g n e d t o t h e S e -h l f yp n o s i s o r J o h r e i) g rou p ,
Self-h y p n o s i s t r a i a n i d n g p r a c t i c e g r o u p , a n d
J o h r e i t r a an i n d i pn ract g ice grou p .
R an d omi s at i on u t i l i s ed ran d om n u mb ers gen erated b y a res earch er b lin d with a co mp u ter.
I t w a s p e r f o rm e d b y u s in g s tu d y n u m b e r s a t r e c r u i t m e n t, an d t h e n t h e s a e n o n ym i s e d
p articip an t s were as s i gn ed t o on e of th e g r o u ps. Alth ou gh th e in itial n u mb er of p eo p le in each
g r o u p at ran d omi s at ion g e n e r a t e d b y a c o m p u t e was r al m os t eq u al , s o me s u b jects with d rew
b e f or e t h e t r a in i n g s e s s was i o n s tart ed (i . e. th e y d id n ot tu rn u p th e firs t s es s ion ) re s u ltin g in
d i f f e r e n t n u m b e r s o f p a r t i c i p a n . t T s h e r i e n w e r a e c 23 h p art g r ici o u p an ts in th e Self-h yp n os is
a n d 16 pa r t i c i p a n t s i n t h e J o h r e i a n d 24 in th e w a i t -listed c o n trol gr ou p s . T h e p s yc h ological
in terven ti on s were ad mi n is tered t o s ev en Self-h y p n o s i s an d eigh t J oh rei t r a i n i c on hg ort s .
A t r e c r u i t m e n t ( B a s after e l i the n e ) i a n n t d e r v e n p t e i r o i n o (a d f t e r 4 m o n t ) h s [ F i g u r ], e th e 7
p a r t i c i p a n t s w e r e a s k e d t o c o logical m p l e qt ue es tp ion s y nc ai h res o . Of 6 3 p atien ts , a total of
t w e l v e p a t i e n t s e i t h with e r d rew f r o m t h e s ot r failed u d y t o c omp let e s ome of q u es tion n aires
b e f o r e t h e e n d o f o n e t -mon h e th t r a i n i n g s e s s i o . n Hen s ce, a tot al o f 51 s u b ject s ( 2 1 i n S e l -f
h y p n o s i s , 1 2 i n J o e h i r a n d 1 8 i n w a i t-l is te d con trols ) c o mp leted q u es tion n aires . Lymp h oc yte
s u b p o p u l a t i o n a n d H I V v i r a l l o a d d a t a w e r e o b t a i n -e e d xis f tin r g o m p at t ien h e t dp at r ab e as e, a n d
o n l y 3 8 s u b j e c t s ( 1 5 i n S -h e l yp f n o s i s , 1 0 i n J o h r e i a n d 1 3 i n w a i -l t i s t e d c o n t r o l g r o ) u hp ad
s
P h . D . a t U n i v e r s i t y o f L o n d o n - 5 7 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
s u f f i c i e n t d a t a f r o m w h i c h t o c a r l a c t u e l a o t f e d t e h c e l i n e Ci D4 n T-c t h e l l s d u ri n g th e s tu d y
p eriod .
- Recruitment - - Post-intervention -
B a s e l i n e T e r m o n e
T e r m f o u r
T r a i n i n g
1 m o n t h
F i g u r e 7: T i m i n g o f t w h o e m e a s u r e m e n t p o i n t s R ( e cr u i t m en t a n d P o st-i n t e r v e n t i o n ) wit h r e ga r d t o t he p e r i o d o f t r a i n i n g a n d f t he p r p a s yc c t h i o lo c e gi c o a l i n t e r v e n t i o n s
2 . 1 . 3 C a s e m a t c h e d p a t i e n t s f r o m t h e d a t a b a s e
Th e s a m e H I -in V fected i n d i v i d u a l s r e c r u i t e d t o t h e a b o v e w R e r C e an T al s ys t eu d iy n
th is cas e con trol led s tu d y. T h e p r e v i o u s R C T s t u d y ed u a s w a i t -listed c o n t r o l g r o u p , s f o t e r a t h e
f o u r mon th s of th e wai ti n g p e r i o , d th e y w ere ran d o ml y as s i gn ed to eith er t h e l f-h S yp n os is or
J o h r e i t r a i g n r i o n u o g p v e r t h e A u g p u s e t r 2 0 i 0 3 o t d o D f e c r e m o b . e Th m r is 2 in 0 creas 0 4 ed th e
n u m b e r i n t h e t w o g r o u p s :
Self-h y p n o s i s: 3 4 s u b j e c t c s o n s i s t in g o f s e v e n t r a i n i n g c o h o r ts
J o h r e i : 2 9 s ub j ects con s is tin g of eigh t t rain in g co h orts
In ad d it ion to th es e p art ici p an ts , 5 8 m a t c h e d d a t a b a s con e trol p at ien ts were s el ect e d
b l i n d l y f r o m t h e s a m e H I V p a t i e n with t d pa ermi t a b a s s ie on fr om th e Et h i c s c o m m i t te e . Th is
s election was p erf or med b y a n i n d e p e n d e n t lan r W . e s S t e a e l r th , c e w h i t h d o c t o r , D
f o l l o w i n g i n c l c u r s i t o e : r n i a
1 . C D4 T-c e l l c o u n t s > 2 0 0 c e l ls / L
�� �� �� Practice & Follow-ups
2 . HIV vi ral l oad > 1 0 0 0 v i r a l c o p i e s / m l
3 . Stu d y p eri od – s a m e 1 2 m o n t h s s p r e a d t o m i n i m i s e s e a s o n a l variati on ; an d th i s
r e s u l t s i n e i g h t c o n t r o l c o h o r t s w i t h r e g a r d t o c o m m e n c i n g m o n t h f o r a n a l y s i s
4 . Eq u ival en t m e a n C D 4 -l y m T p h o c y t e s c o u n t with s tha t of p art ici p an ts at th e
com men ci n g m on t h of t rai n in g in terven ti on .
3 m o n t h s
C D 4 -c T ell c ou n ts an d vi ral load le vels w ere ob tain ed fr om th e p atien t d atab as e. Th e
T r a i n i n g t i m e p o i n t w a s s e t a s t n h e -m m o n i t d h p to rai i n it n g io nf terven t h e ti on o s an d
s u b s eq u en t t erms were n amed aft er th e n u mb er of m on th s fro m th e Tr ain in g time p oin t (e.g.
T e r m o n e i s o n e m o n t h f r o m t h e a i T n r i n g t i m e p o i n t Figu ) [ re 8].
P h . D . a t U n i v e r s i t y o f L o n d o n - 5 8 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Training
B a s e l i n e T e r m o n e
T r a i n i n g
1 m o n t h
3 m o n t h s
Fi gur e 8: Ti m e-points (Tr a inin g t ime point and the T e r m s a cc or din g t o th e T r a i n i ). n g
In t e r v a l s b e t w e e n t -l h i e n e s d o r e t p e r e d s e n t o n e t e r m ( o n e m o n t h )
Th e C D4 ch an ge grad ien ts were co mp are d b e t w e en t h e i n t e r n v e n g t r i o o u p elf- s ( S
h yp n os is an d J oh rei ) an d t h e d a t a b a s e c o n t r o l g r o u p . F o r e a c h i Cn D4 d i v di ecl d u ia nl e , a
g r a d i e n t (cel ls p er l p e r m o n t h ) was c a l c u l a t retros e d p ect ivel y f ro m th e p reced in g 1 2 m on t h s’
d ata h el d on th e p at ien t record d atab as e (P r e-i n t e r v e n t i o n ) . T h e -in s e ter p ven r e ti on C D4
g r a d i e n t s w e r c o e m p a r ed b e t w e e t n h e t h r g e r e o u p s. S i m i l a r l y, a p o s t-i n t e r v e n t i o n C D 4 g r a d i e n t
w a s p r o s p e c t i v e l hy e C D4 c a gl rad c ien u l ts a in t th e d 1 2 . mon T th p eriod s p rior to an d after th e
T r a i n i n ( g P r -i e n t e r v e n t vs i . o P n o s t-i n t e r v e n t i o n ) [ F i 9] g were u r e co mp ared wi th in an d b etween
th e th ree gr ou p s .
Training
Pre-i n t e r v e n t i o n
4 m o n t h s
Fi gur e 9: C o m p a r i s o n f or m a t wi t h r e ga r d to t h e T r a i n i n g t i m e p o -i i n t t e rve ( n P t i r o e n vs . P o s t-
int e r ve nt io n ) . Int e r va l s be t we e n do t-l i n e s r e p r e s e n t t o e n e r m ( o n e m o n t h ) a s i n F i g u r e 8
Seven p a t i e n t s t h i Self-hy e n p n o s i s grou p , ten p at ien ts in th e J o h r e i g p r an o u d n in e
p a t i e n t s i n D a t -c a b o a n s t e r ls o were excl u d ed b ecau s e n o rou tin e b lood s amp les wer e taken
d u r i n g t h e 1 2 m o n t h s e i t h e r p r i o r t o o r a f t e r . In i th n es t e r exc v e ln ut d ed i o pn at ic en o m ts , m e n c e d
s e v e r a l p a t i e n t s c o m ed m e a n c t i -r e t r o v i r a l m e d di uc rin a t g i th o e n P o s t -i n ter ven ti o n p eriod , an d
the y were d r op p ed fro m t h e s tu d y. Tab le 5 s h ows th e n u mb ers of p atien t s wh o s tar ted d ru g
th erap y i n e ach gr ou p .
�� �� �� Practice & Follow-ups
T e r m f o u r
Post-i n t e r v e n t i o n
T able 5: N u m b e r and month of su bje ct s wh o s ta rt e d a nt i -r e tr ovir a l m e d i c a t i ao nd n dr oppe d fr om the
s t u d y ( N B : T er m X r ep r e s e nt s t ha t X m on t hs a f te r t he R e cr u i t m en t t i m e p o i n t )
T e r m 2 T e r m 5 T e r m 8 T e r m 1 1 Total
D a t a b a s e c o n t r o l s 0 1 3 3 7
S e l f-hypnosis 0 0 2 4 6
J o h r e i 1 0 1 1 3
P h . D . a t U n i v e r s i t y o f L o n d o n - 5 9 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
2 . 1 . 4 L a b o r a t o r y v o l u n t e e r s
T h i r t y o h n e a l t h y v o l u n te e r s, o f wh o m 2 1 were mal es an d 1 0 f e m a l e , s with a n a g e r e a n g
of 2 1 -6 0 y e a r s, were recru i t ed to d on ate b lood in o rd er to in ves tigate th e eff ects o f i n v i t r o
e x p o s u r e t o t h e s t r e s s -c e l h l o s r -l m a y o m n p n d h e o c T y , t s. e c o r t i s o l , u p o
Th is recru it men t was t h r o u g h w o -o r f d -m o u t h c o n t a c t s w i t h t h e a u t h a o n r d c o l l a g e u es
f r om th e Dep art men t o f Immu n olo g y an d th e Di v i s i o n o f N e u r o s c i e n c e a n d M . All e n t a l H e a l t h
b lood s amp l es were col l ect ed b etween 9 :3 0 an d 1 1 :3 0 a.m . to elimin ate th e e ffects of d iu rn al
variati on [ M c G l o n e e t a l . , 1 9 9 a 1 n ] d t h e n e i t h e r i s o l a t p e r d i p h e r a l b l o o d m o n o n u c ells l e a r c
(P BMC s ) or wh ol e b l o od wer e a s s a yed s t raigh t afte r c ollection .
2.2 P s y c h o l o g i c a l in t e r v e n t i o n
2 . 2 . 1 S e l f-h y p n o s i s t r a i n i n g
T h e s e l f-h yp n os is trai n in g, d es ign ed an d c o n d u c t e bd y an exp eri en ced cl in ical h yp n otis t
D r . T a n n i s M . L a i d l a w , c o n s i s t e d o o u f r f w e e k l y s e s s i o n ( s t w o h o u r s e a c h . )
T h e p a r t i c i p a n t s l e a r n t f i r s t a S p i e g e l-t y p e e y -roll e in d u ct ion (s yn ch r on is in g u p ward e y e -
r o l l s w i t h a d e e p i n s p i r a t i o n f , r o f m o l t l h o e w e n d o s e b y h o t l h d be i reath n g fo r a f e w s e c s, o n d
t h e n e y -r e o l l s d o w n w i t h ti e on x p i fr r om a th e mou th ) f o r ‘ i n s t a n t r .’ e Th l a e x y a t w i e o r n e a l s o
t a u g h t a s l o w e r r -t e yp l e a x in a dt ui ct o ion n tech n iqu e to ach ieve gettin g in to a s tate o f min d ,
‘h y p n o t i c s t .’ a t A e l l p a r t i c i p a n t s w e r e p r o v i d e d w i -rec t h ord a in s g t [Ap a n p d e a n r d i x a 2-i] u d i o
w h i c h p r o v i d e d i n s t r u c t i o n s f o r b o t h i n d . u Pc reviou t i o n s res ear ch h as s h own th at u n ivers it y
s tu d en ts p ract i s i n g i mmu n e s tren gth en im ager y in th e self-h yp n os i s t rain in g h ad les s cold
s y m p t o m s d u r i n g i r t h e a c a d e m i c e ination x a m p e r i o d t h a n s t u d e p n r t a s c t i s i n g r e laxa ti on ima ger y
[ Gru zel ier, L e v y e t a l . ]. It 2 0 w 0 1 a s a l s ho own in p at ien ts wi th gen ital h erp es th at s elf h yp n os is
c o n t r i b u s t e t o a r e d u c t i o n i n -relat d i s ed e a s se ymp toms [F o x e t a 9 l 9 9 . ; 1 G r u z e l i e r e t ]. a l . 2 0 0 2
H e n c e , the i n d u c t i o n t e c h n i q u e w mb a s in l ed a wi t e th r a sc po eci fi c ima ger y of i mm u n e
s t r e n g t h e n , i wh n g ich p art ici p an ts were to ld to p r a c t i s u e n d e r t h e h ‘ y p n o t i c s t ’. a t Fu e rth er, al l
p a r t i c i p a n t s w e r e t a a n x u i g e h t t y m t a n w a o g e m e n t t e c h n i q u e s :
1 . How t o u s e b reat h in g tech n iq u es to con tr ol acu te an xi et y [ L a i d l a w , 1 9 9 4 ; ] an d
2 . Th e I n t e ru p t Di s tract ion P roced u re ( IDP ) [ L ai d l a w , 1 9 9 9 ] for w orri es an d b el ief c h a n g e .
P h . D . a t U n i v e r s i t y o f L o n d o n - 6 0 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Each p art ici p an t wa s r e q u e s t e d to p r a c t i s e l f-h yp n o s i s d a i ly t o learn an d fa miliar is e
th ems el ves wi th t h e t e c h n i q [ u G e r u z e l i e r e t a l . , 1 9 9 . 8 D ] u r i n g o n -mon e th trai n in g p eri od , each
p a r t i c i p a n t a t t e n d e d f o u r g r o u p s e s s i o n s w i t h t h e h y p n o t i s t a n d e a c h w a s e x p e c t e d m, t o at p e r f o r
l e a s t , m o r e t h a n t e n s -h e l yp f n os is s es s ion s . Diar i e s w e k r e p t b y t h e p a r t i c i p a n t s t o r e c o r d t h e i r
p r a c t i c e f r e q at u e hn ome c y . Aft e r th e f ou r wee kl y t rain in g s es s ion s , m o n t h l y -u p f g r o u l p l o w
s es s ion s were c o n t i n e d u f o r a t l e a s t f o u r m o n b t h y s -inf H e I c t V e d i n d i v i d u . a l s
2 . 2 . 2 J o h r e i t r a i n i n g
Th e J oh rei trai n in g was p lan n ed an d c o n d u c t e bd y th e au th or wh o is a t rai n ed p ractition er
with more t h an 2 0 yea rs o f p ractice an d wh o is als o med icall y q u ali fied . O rigin al teach in g
t e x t b o o k s a n d s u p p o r t w id e ed r e b y p t hr e o Jv oh rei Acad em y [h t t p : / / w w w . j o . h r u e k/] i an . d o r g
J o h r e i A s s o c i a t i o n h [ t t p :/ / w w w . j o h r e ia s s o c i ation.co. u k/] s o t h a t t h au e th or cou ld t each , ed it an d
a d j u s t for each g rou p o f p art icip an ts in th e s tu d ies [Ap p e n d i x 2-ii] [ See al s o th e J o h rei
F o u n d a t i , o h n t t p :/ / w w w . j o h r e i f o u n d a t i o n . o r g /; I z u n o m e, h t t p : / / w w n w . o i m z u e . o r g ; / j o h r e i .
a n d J o h r e i i n s t , i h t t p u :/ t / e w w w . j o h r e i-i n s t i t u t e . o r g / o u r p ] e o p l e . a s p
Th e J oh rei i n t erv en t i on con s is ts of fou r w eekl y train in g s es s ion s (tw o h ou rs each )
i n v o l v i n g c o r e p r in c i p l e s n e e d e d t o t p i r s a e c J o h r e i t e c h n i q u e s s h u e c a h l i a g s n o n“ es el f b y
h e a l i n g o t h e ”; r s s tate of h a r m o n y, b al an ce an d timin g (I Z U N O M E), an d an in trod uction to the
th ree fou n d at i on s of J oh rei p h ilos op h y w h ich emp h as is es imp ortan ce of :
1 . Aw a r e n e s s o f s p i r i tu a l w e l l-b e i n g (Ar t o f livin g / Ar t o f He a l i n ); g
2 . Ap p r e c i a t i o n o f a e s t h e t i c A s r ( t a n d B e a ) u t ; y a n d
3 . Ap p reci at ion of Na t u r e i n c l u d i n g f a r m i n g p r a c t i c A e r ( t o f N a t ). u r e
I n J o h r e i p r a c t i , c e t h e p r a c t i t i o n e r i m a g n i n e t e h s e r e a l ‘h e a l i n -light’ g e n t e r i n g dh y i s b o
an d b e i n g t r a n s m i t t e d t h r o u g h h i s / h e r h a n d s t o w a r d s t h e r tition e c i p er i , e wi n t t. h ou T t h e p r a c
tou ch in g a reci p i en t , s l owl y mo ves h is /h er h an d s from th e h ead d own t o th e kid n e y area, fr on t
an d b ack. Th e p roced u re t a kes ap p ro xima tel y 1 5 min u tes in s ilen ce. Th e p articip an ts were
r e q u e s t e d t o p r a c t i s e J o h r e i d a i l y w i t h a p a r t n e r , b u t a t t h e e n d o f t r a i n i n g p -J e r oh i o rei d , an s e d l f
d is tan t J oh rei t e c h n i q u s e we r e in trod u ced as s u p p l e m e n t a r y t o o l s s o t h a articip t p an ts cou ld p ractice w h e n a p a r t n e r w a s n o le.
t a v a i l a b
P h . D . a t U n i v e r s i t y o f L o n d o n - 6 1 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
As in th e h yp n os is gr ou p , it w a s r e q s t u e d t h a t e a c h p a r t i c i p a n t p ractis e J oh rei at l eas t
f o u r t i m e s a t o lea w e rn e k an d fami li ari s e th ems elves with t h e t e c h n i q . u Diaries e w ere u s ed to r e c o r d p r a c t i c e f r a e t q u h e o n m . c Grou y e p mo n t h l y -u p f s e o s s l s i l were o n o w c o n t i n ed u for at
leas t fou r mon t h s .
2 . 2 . 3 M o c k i n t e r v e n t i o n ( C o n t r o l s f o r t h e p s y c h o l o g i c a l t r a i n i n g s )
T h is m o c k n e u r -f o e e d b a c k c o n d i was t i o ai n med to p r o v i e d a c o n t r o l a g a i n s t p o s s i b l e
p l a c e b o e f f e c ts f r o m p a r t i c i p a ’ n t e s x p e c t a t a i n d o n a g a i n s t fa c t o rs o f at ten tion give n an d
e x p e r i e n c e o f r e l a x a d t u i r o i n th n g eir trai n in g s e s s i o n s s in ce th is p roced u re w a s s h own to
gen erat e a rel a xat ion r es p on s e wh en u s ed as a c on trol c on d ition [ E g n e r e t a l . , 2 0 0 . 2 ]
T h i s c o n d i t i o n a p p e a b e r e h d i g -t t h ech o , wi th two c omp u ters an d electrod es fi xed to
e a r l o b es a n d t h e c e n t r e o f , an t d h wi e th s c au a dl it p or y rel a xi n g feed b ack s ou n d s (b ab b lin g
b roo k an d ocean wa ve) h eard o ver h ead p h on es . Th e s ou n d s were s u p p os ed ly rep re s en tin g alp h a
a n d t h e t a w a v e eed f b ack fr om th e p art ici p an t ’s own b rain waves as s ociated with r elaxation .
Alth ou gh t h e p ro ced u re was real , th e feed b acks were fals e as th e s ou n d s were r eco r d ed
p r e v i o u s l f r y o m a n o t h e r s e s s ion .
T h e pa r t i c i p a n t s is g i r n o u p t h a d e i g h t m o c -f k e n e e d b u a r ck o s e s s i o n s o v e r o n , e m o n t h
an d th es e s es s i on s were p erfor med b y Dr . Dwived i, a q u alified clin ical p s ych ol ogis t, with valid
n e u r o-feed b ack eq u i p men t .
2.3 S e l f-r e p o r t u e s q t i o n n a i r e s
P r i m a r y a p p r a i s a l i n s t r e s s p e r c e p t i o n ( a n x i e t y l e v e l a n d i m p a c t es o f s fu a l s et r ven t ),
s e c o n d a r y a p p r a i s a l en , s e o f ‘t a k i n g c o n t r o l o ’s f o w n e n l ’, i f pe s ych ol o gi cal fu n ct ion in g
(m e n t a l q u a l i t y ) o f a n l d i f s e l e e p q u a l i t y w e r e m e a s u t r h e f o d ll owi b y n g u s pi u bn lg is h ed
q u es tion n ai res .
P h . D . a t U n i v e r s i t y o f L o n d o n - 6 2 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
2 . 3 . 1 S t r e s s p e r c e p t i o n
2 . 3 . 1 . State 1 a n xi e t y s c o r e i n t h e a S n t d a t T e r a i t A n x i e t y [S I p n i v e l n b t e r o g r e r y e t a l . , 1 9 7 0 ]
T h e S t a t e a n d T r a i t A n x i e t s y c a l I e w n v a e s n d t e s o i r g y n d e t o m e a s u r e t h e l e v e l s o a f n x i e t y
b o t h a t t h e e x a c t t i h m qe ue es tion n ai re w as fi ll ed in (s tate an xiet y) an d as a gen era l ten d en c y
(t r a i t a n ). x State i e t y an xi et y le vel w as me as u red an d an al ys ed in th e cu rren t p roject . High s co res
a r e a s s o c i a t e d w i t . h a n x i e t y
2 .3 .1 . 2 I m p a c t o f E v e n t S c a l e ( I E S [Hor ) owi tz et al ., 1 9 7 9 ; J os ep h , 2 00 0 ; Sun d in & Hor o witz,
2 0 0 2 ]
Th e Imp act of Even t S cal e ( IES) meas u re s th e amou n t of s t res s wh ich res u lt s fro m a
p s ych ol ogi cal l y tr au mat is in g e ven t, s u ch as a d iagn os is o f H I V i n f e c . t High i o n s co res are
as s ociat ed wh en e v e nt b e i pn ercei g v ed as a s tres s or . Th is IES was meas u red an d an al ys ed in th e
s t u d y u -in s fect i ed n g in d ivi H dI u al V s in th is cu rren t p roject. Hi gh s cores are as s oci ated with
h igh i m p a c t o f t h e e v e n t.
2 .3 .1 .3 P e r c e i v e d S t r e s s S c a l e ( P S S [ ) C o h e n e t a l . , 1 9 8 3 ]
Th e P e r c e i v e d S t r e s s S c a l e PSS) ( is a s ca le d es ign ed to meas u re th e s e c o n d a r y ap p rais al
of s tres s ove r a p eri od (t w o wee ks or a m on th ) with t h e d e f i n i t i o n p er t ceived h a t “ st r es s is th e
d e g r e e t o w h i ch s i t u a t i o n s i n o n e ’ s l i f e a r e a p p r a i s e d a s s t r e s s fu l (un pr ed ict ab le, un co n tro ll ab le
a n d o v e r l o a d .” i n H g i g h s c o r e a s r e a s s o c i a t e d w i th s t r e s . s
2 .3 .2 P e r c e i v e d q u a l i t y o f l i f e
2. 3. 2 . 1 L o c u s o f C o n t r o l s c a l e ( L o C [ F ) u r n h a m & S t e e l e , 1 9 9 3 ; W a l l s t o n e t a l . , 1 9 7 8 ]
Th e L o c u s o f C o n t r o l s c a l e L ( o C) meas u res th e p ercep ti on o f c a ability p o f c o n t r o ll i n a g
e v e n t [ S c h m i t z e t a l . , 2 0 0 . 0 Low ] s c o r e s are as s oci at ed with h igh s en s e o f takin g c on trol of
o n e ’s own li f e, as s a l ed f r o m 0 ( t o ter t a n l a l ) y t i o n 2 4 ( t o t e r a n l a l ) y [ R o e t x t e r , 1 9 6 7 : ]
I n d i v i d u a l s w h o h a v e i n a t e n r n a l l o c u s o f c o n t r o l b el ieve th at even ts res u lt p rimari l y
f r o m th ei r own b eh avi ou r an d action s .
T h o s e wh o h a v e a e n x t e r n a l l o c u s o f c o n tr o l b e l i e v e t h p a o w e r f u l o t h e r p a r t n e r s , f a t e
o r c h a n c , e p ri mari l y d et er mi n e even ts . H i g h s c o r e s a re as s o ci at ed wi th low con tr ol.
P h . D . a t U n i v e r s i t y o f L o n d o n - 6 3 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
2 .3 .2 . 2 Men tal C omp on en t Su mma r y in th e S F -3 6 ( M C S ) [ W a r e e t a l . , 1 9 9 * 4 ]
T h e S -3 F 6 is a s cal e d evel op ed t o m e a s u r e t h e l e v o e f l s q u a l i t y o f . Th l is i f c e o n s i s t s o f
two s u b s et s , i .e. Ph ys i cal an d Men tal h eal th clu s ters as s c a l e s of th e P h ys ical C omp on en t s
S u m m a r y ( P C S ) t a n h d e
M e n t a l C o a m r p y o ( n M e C S n ) . t s H s c i o r g e h s iS n eac u m h m s u bs et are
a s s o c i a t e d a w h i igh t h p ercei ved q u a l i t y o f p l h i y s f i e c al l y ( P C S ) a n d m e n t a l l y ( M C , S )
r e s p e c t i . v e l T y h e M C S w a s m e a s u r e d a n d -in fecte a n d a il n d iy vi ds u als e d i n t h e
in th is cu rren t p roj ect . H i g h s c o r e s a re as s oci at ed wi th h igh p s ych ol ogi cal fu n ction in g.
2 .3 .2 . 3 P i t t s b u r g h S l e e p Q u a l i t y I n d e x ( P S Q [ B I ) u y s s e e t a l . , 1 9 8 9 ]
T h e P i t t s b u r g h S l e e p Q SQI) u a l i s t a y s I c a n l d e e d x e v e ( l P o p e d t o m t e h a se s u br ject e ive q u a l i t y o f c s o m l b e i e n p e d w i t h b e h a v i o u r a l i t e m s, e . g . s l e e p . d H u r i g a h t i s c o n r are e s
a s s o c i a t e d low w i t s l h e e p q u a l . i t y
All s e l f-rep o rt d at a a n o n ym i s e d a n d d e p e r s o n a l i t o s p e r d o t e c t t h e c o n f i d e n t i a l i ty of th e
s tu d y p art ici p an ts . Al l d a t a c o l l e an c t d i en o n tr y was p e r f o r m e d b y r e s e a r c h a s s i s t a bn lin t s d to t h e t r e a t m e n t c o n d i t i o n s o f t h e s t u d y p a . r t i c i p a n t s
* N o t e : T h -3 e 6 sS cal F es , in cl u d in g t h e M e n t a l C o m p o n e n t S (MC u m m S) a r , ar y e
s c o r e d s u c h t h a t r h i s cores g h e rep res en t b et ter fu n ction in g (in th is cas e, h igh er
p s ych ol ogi cal fu n ct i on i n g), an d low er s c ores r ep res en t p oore r fu n ction in g. In all o f
t h e o t h e r a s m u e r em e n t s u s e d i n t h i s s t u d y , h i g h e r s c re o r e s f u r n e c p t r i e o . s n e i n t g p o o
2.4 M ater i al s a n d m e o t d h s f o r i n v i t i r n o v e s t i g a t i o n
2 . 4 . M 1 a t e r i a l s a n d e x p e r i m e n t k i t s
2 .4 .1 .1 C h e m i c a l s a n d r e a g e n t s
Th e fol l owi n g M a t e r i a l s w e r e
h t t p :/ / w w w . s i g m a a l d r i c h . c o m /)
R P M I 1 6 4 0
1 % g l u t a m i n e ( 2 0 0 m M )
p u r c h S a i s g m e a (D d ors et , f U . r K., o m
1 % p en i ci l l in (5 0 00 IU/ ml ) / s t r e p t o m y c i n ( 5 0 0 0 m c g / m l )
1 % H e p e s b u f f e r
P h . D . a t U n i v e r s i t y o f L o n d o n - 6 4 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
1 % n o n-e s s e n t i a l a m i n o a c i d s ( 1 0 0 x )
1 % s od i u m p yru v at e (1 0 0 mM) .
F o e t a l c a l f s e r u m ( F C S )
P h o s p h a t e b u f f e r s a l i n e ( P B S )
L y m p h o p r e p® (f o r p e r i p h e r a l b l o o d m o n o n u c l e a r c ) e l l s s e p a r a t i o n
P a r a f o r m a l d e h y d e ( P F A )
0 .0 5 % E o s i n d y e
P r o p i d i u m i o d i d e ( P I )
P h y t o h a e m a g g : l m u i t i o ) g e n i n ( P H A
S t a p h y l o c o c c a l e : n s t u p e r r a n o t i t g e o n ) x i n B ( S E B
H y d r o c o r t i s o n e
R a d i o a c t i v e [
3 H] th ymi d in e w a s p u r c h a s e d f r o m Am t h ers e h am [Ame rs h am P h armacia
B i o t e , c B h u c k i n g h a m s h i , r U e . K., h t t p :/ / w w w 6 . a m e r s h a m b i o s c i e n c e s . c o m /]
2 . 4.1 . 2 B i o l o g i c a l r e a g e n t s
T h e a n t i g e n s o f p u r o i t e f i n e d e r p i v a t i ( v e P : t P u b D e r c u l o s i s a n t i ) g e an n d Herp es
S i m p l e x v i r u s c o m m o n a n t i g e n ( H e r p e s ) w e r e p r o olo v i gd y e cl d in b ical y lt ab h orat e I or m y m u n
at C h el s ea an d Wes t mi n s t er hos p ital.
Th e K 5 6 2 c e l l l , a i n e hu man ch r on ic m ye logen ou s leu kae mia cell lin e f or N K c yt o toxic
a c t i v i t y m e a s u r e m e n t, was p u rch as ed fro m th e E u r o p e a n c o l lection of cell cu ltu res [E C A C C ,
Salis b u r y, U. K. ].
2 . 4.1 . 3 F l u o r e s c e n t l y c o n j u g a t e d a n t i b o d i e s f o r f l o w c y t o m e t r y a n a l y s e s
An t i b o d y c o c k t a i l s -F o f I T C C/ D C 4 D 5 3-P E / C D 4-C y -C h r o m e/ C D 8-A P C a n d C D -4
5
F I T C/ C D 3-P E / C D 1 9-C y -C h r o m e/ C D 5 6-AP C , stan d ard p an els of flu ores cen tl y co n ju gated
a n t i b o d y c o c k t a i l s f o r t e l s y u m b p o h p o u c l y a t i o n a n a l y , s we e s re p u rch as ed fro m B e c k m a n
C o u l t e r [B e c k m a n C o u l t e r, B ed ford s h ire, U. K., h t t p :/ / w w w . b e c k m a n c o u l t e r . c o m /]
In d i v i d u a l a n t i b ies o d o f C D 3 , C D 4 , C D 8 , C D 4 5 9 5 , N k C p 0 D 3 , 5 6 , C D 1 6 ,
N k p 4 6 a n d A ( n c o n j e u g x a t i e n d w i V t h F I T -C C , h r o P m E e , o C y r A P C ) w e r e p u r c h
B e c t o n D i c k i n s o n [B e c t o n D i c k i , n Os xo ford n , U . K., h t t p :/ / w w w . b d . c o m /] .
P h . D . a t U n i v e r s i t y o f L o n d o n - 6 5 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
2 . 4.1 . 4 C o m m e r c i a l l y a v a i l a b l e l a b o r a t o r y k i t s f o r c o l o r i m e tr i c m e a s u r e m e n t
T h e C y t o T o x ®, 9 6 a kit me as u ri n g N K c yt ot o xic a c t i v i t y , Pw ro a mega s p u r c h a s
[P romeg a U. K., h t t p :/ / w w w . p r o m e g a . c o m /]. T h i s C y t o T o ® x 9 a 6 n a l y sis i n c l u s d e m e a s u r em e n t s
o f r e l e a s ed L a c t a t e d e h y d r n o a g s e ( L D H ) in t h e s u p e r n a n t o f t h e c u i l u t m u r ( e a d f t -h m e ou e r d r 4
i n c u b a t i o n o f mix ed K 5 6 2 c e l l s a n d P B M C s ) w h i c h c o n t a i certain n s level s o f LD H fr om d ead
cells. Th is ki t was u s ed i n o r d e r t o a v o i d u -active s i n g sr u ba sd tan i o ce wh ich is requ ired in th e
gold s tan d ard met h od , th e 5 6 C r -r e l e a se a s s a [ y P r om e g a , 2 0 0 4 ].
E L I S A k i t s f o r m e a s u r i n g -S an t d mel h e at on il n were e v pe u rch l as s ed o f c o r t i
fro m i DS [iDS U . K., h t t p :/ / w w w . i d s l t d . c o m /].
2 . 4 . E 2 q u i p m e n ts u s e fo d r i n v i i t r n v o e s t i g a t i o n
2 . 4 . 2 . F 1 l o w c y t o m try e
Fl ow c yt o met r y i s a meth od f or q u an titatin g co mp on en ts or s t ru ctu ral f eatu res o f c ells
p rimari l y b y op ti cal mean s . F l o w c y t o m e m t e r a y s u r e s on e c el l at a ti me, b u t it can p roces s
t h o u s a n d s o f c e l l s i n a f e w s e c o n d s . T h e c e l l s -f a r i l e p t h a rou s s gh e d a s las i n er g l be eam b y
con tin u ou s fl ow o f a fi n e s t ream o f th e s u s p en s ion . Each cell s catters s o me of th e l as er ligh t,
a n d a l s o e m i t s f l u o r e s c e n t l i g h t e x c i t e d b y t h e cl oa me s e r f ro m th e lab el led fl u ores cen t
c o n j u g a t e d a n t i b o d i e s d e s i g n e d t o b o n d r s t p i e c i l f e i c o n p a t h e c e l l s u r f a c e o r i n . t h e c y t o p l a s m a
T h e f i v e m a i n c o m p o n e n t s o f f l o w c yt o m e t r y a r e :
1 . Fl ow cel l - l i q u i d s t ream (s h eath flu id ) ca rries an d align s th e c e l l s s o t h a t t h e y p a s s i n
s i n g l e f r i l o e u t g h h t h e l i g h t b e a m
2 . Li gh t s ou rce - c om mon l y u s ed is h i g h p o w e r w a t e -c r o o l e d a r g o n a n d / o r k r y p t o n l a s e r
3 . El e c t r o n i c d e t e c t o r w h i c h c a n q u a n t i t a t e t h e f a i n t f l a s h e s o f s c a t t e r e d a n d f l u o r e s c e n t l i g h t
4 . A n a l o g u e t o D i g i n vers t a l i on C ( o ADC ) s ys te m wh ich g e n e r a t es f o r w a r d s c a t t e r (FSC)
an d s i d e s c a t t e r SSC) ( s i g n a ls as wel l as l ab el led f l u o r e s c e n c e s i g n a l s
5 . Comp u ter f or an al ys is of th e s i gn als , an d to r e c o r d ata d for th ou s an d s of cel ls p er s amp le,
an d to d i s p l a y t h e d a t a g r a p n h d i c n a u l m l e r y i c a l l y
6 . Stat is ti cal an al ys is c an b e d on e s i m u l t a n e o u s o l r y a f t e r w a r d u a s n i a l n g y s i a s n p r o g r a m m e
P h . D . a t U n i v e r s i t y o f L o n d o n - 6 6 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
D a t a a c q u i s i t i o n
Th e c yt o met e r t yp i cal l y m eas u res s ever al p aramete rs s imu ltan eou s l y f or e ach cell :
Lo w a n g l e f o r w a r d s c a t t e (F r S C ) in ten s it y, p r op ort i on al to cell d iameter
Or t h o g o n a l ( 9 0 d e g r e e ) s c a t t e r i n t e n s i t y orti , on a p al p r to o tx hi e m q ua an t e ti l ty y o f p r o p
g r a n u l a r s t r u c t u r e s w i t h i n t h e c e l l ( S S C )
SS C
Fl u o r e s c e n c e i n t e n s i t i e s a t s th e v s e r a l w a v e l e n g
(each FL-1 , -2 F , L -3 F L a n d s o as o sn ocia te wi th a
d efin ed s t ru ct u re i d en t i fi ed b y a f l u o r e s c e n t p r o b e )
L i g h t s c a t t e r a l o n e ( F S C a n d S S C a p g h r : e . g . F i g 1 u 0) r e
is com mon l y u s ed t o ex cl u d e d ead cells , cell ag gre gates , an d
cell d eb ri s fro m t h e fl u o res cen ce d ata. It i s s u fficien t to
d i s t i n g u i s h l y m p h o c y t e s f r o m m o n o an c y d t e gran s u loc yt es in Debris
Granulocytes
Lymphocytes
Monocytes
b lood leu koc yt e s a mp les . F i g u r e : 1 FS 0 C v s . S S C d o t p lo t
Flu or es cen ce i n t en s i t i es are t yp icall y mea s u red at s everal d i f feren t wa velen gth s
s imu ltan eou s l y fo r each cel l . Flu ores cen t p rob es are u s ed to r ep ort th e q u an tities of s p ecific
c o m p o n e n t s o f t h e c e l l s . F l u o r e s c e n t a n t i b o d i e s a r e o f t e n d en u s iti e d es t of o s pr eci e p o fi r c t t h e
s u rface recep t o rs , an d t h u s t o d is tin gu is h s u bp op u lation s of d ifferen t cell t yp es .
G a t i n g a n d d a t a a n a l y s i s
I n o r d e r t o a n a l h y a r s a e c t c e r i s t i c s o f s p e c i f i c i m m u n -p e op c ue lat l il on , s u el b ect io n of th e
c e l l s n e e d s t o b e p r e c i fficien s e a n t. d Th e is s el ect ion is p erfo rmed b y ma kin g a gat e of re gion in
a d o t-p l o t d u r i n g f l o w c yt o m e t r y a n a l ys e s , f o r e x a m p l e :
1 . Aft er s et ti n g u p fl ow c yto meter f or acq u is ition , c r eate a d o t p l o t th w e i X-axi t h s as
f o r w a r d s c a t t e r ( F S C ) a n -a Y d xis t h as e s i d e sc a t t e r (SSC).
2 . A c q u i r e d a t a f r o m c , e l l a s n d r a w cir a cl e arou n d a re gi on of th e l ymp h oc ytes b as ed
o n t h e i r l i g h t s c a t t e r c h a r a c s t on e r i t s h t e i p c l o t ( F S C . SSC v s ). Th is b ecomes a re gi on
1 (R 1 ), t h e red ci rcl e of l ymp h o c yte in th e Fi gu re 1 0 fo r e xamp le.
3 . F o r fu rt h er a n a l y ses , c reate an oth er d ot p l ot th at en co mp as s es th e c e l l s f r o m Rt 1 h in e
t h e p l o t w i t h f l u o r e s c e n t s ( F L 1 v s . S S C o r F L 1 v s . F L . 2 e t c . )
P r e c i s i o o f pe n rcen ta g e in ly m p h o c y t e -p s o u p b u l a t i mea o n s ure d by f l o w c y t o m e t r y
Meth od ol o gi cal vari at i on i n l ymp h oc yte p ercen tages was as s es s ed in th ree p relimi n ar y
b lood s amp l es fr om on e vol u n teer. Nin e s amp le tu b es of b lo od were t aken at each t ime p oin t ,
P h . D . a t U n i v e r s i t y o f L o n d o n - 6 7 - I m p e r i a l o C n o d l o n l e g e L
F S C

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
a n d a s s e s s e d f o r p e r c e n t a g e s o f c e l l s e x p r e C s D s i 4 5 n g
+ C D 3 - C D 5 6 + (h e n c e f -cells) o r t an h d N K
C D 4 5 + C D 3 + C D 4 + + + +
( 4 C D T-cells) a n d C D C 4 5 D 3 C D 8 ( C D 8 T-cells).
F l u o r e s c e n t l y c o n j u g a t e d s D8 i n , Cg D4 l 5 e , C D5 a 6 n an t d i C D1 b o 6 d i e s o f C D
[Bect on Di cki n s on , Oxf ord , U. K. ] wer e u s ed t o d e t e r m i N n K e c e l l (C s yt ot oxi c an d R egu lat or y
N K -c e l l s u b s e t s )
a n d -l y m T p h o c y t e s ( 4 C D -c T e l l s a n -c d e l l C s ). D C8 el l sT amp les were
m e a s u r e b d y a FAC SC al ib u r fl o w c yt o m eter [B e c t o n D i c k i ] n s a o n d th e d at a gen erat ed b y fl ow
c y t o m e t e r w e r a e n a l y s e d b y a C e l l Q u e s t . s o f t w a r e
M e a n s a n d r a n g e s w e r e w i t h i n n o r m a l [ H l i a m n n i e t s e t a l . , 1 9 9 an 2 ] d s tand ard d evi at ion s
were cal cu lat ed in in d ivi d u al o c c a s i o an n d in tot al [T a b l e 6].
Table 6: M e a n p e r c e n t a g e s a n d c o u n t s ( s t a n d a r d d e v i a t i o n : S of D N ) K -c e l l s, C D 4 and C D 8 T-ce lls and
t ota l lymp ho c yt e c ount s us ing a s in gle vo lu nt e e r ( 9 t ube s co lle c t ed a nd a ve r a ge d on 3 s e p a r a t e o c c a s i o n s )
NK % C D 4 % C D 8 % N K count CD4 count CD8 count T ot a l l ym p h c o u nt
( S D ) ( S D ) ( S D ) ( S D ) ( S D ) ( S D ) ( S D )
T ime 1.
T ime 2.
T ime 3.
T o t a l m e a n
( S D )
9.7
(0.54)
8.3
(1.31)
14.3
(0.72)
10.77
(0.86)
48.1
(0.97)
46.8
(0.89)
44.4
(0.52)
46.4
(0.79)
29.6
(0.73)
28.8
(0.33)
28.2
(0.60)
28.9
(0.55)
94.8
(9.3)
65.6
(12.6)
130.3
(8.7)
96.9
(10.2)
438.4
(12.7)
346.1
(10.7)
381.0
(36.4)
388.5
(19.9)
270.0
(11.3)
894.3
(32.0)
P h . D . a t U n i v e r s i t y o f L o n d o n - 6 8 - I m p e r i a l o C n o d l o n l e g e L
213.4
(9.8)
249.3
(11.6)
244.2
(10.9)
712.6
(36.2)
859.2
(33.6)
822.0
(33.9)
H e n c e , l a l c h a n g e s i n p e r c e n t a g e s o f N K c e l -cells l s , a n d C C D D 4 8 -c T e T l l s mo r e th an
twice of s tan d ard d evi at ion s in total mean s , i.e. 1 . 9 0 , 1 . a n 5 d 1 8 . 1 res 0 p ect ivel % y, were
con s id ered as in o u t o f t h e 9 5 % c o n f id e n t i n t e r v a l. C h a n g e s i n e a c h -p c op e l u lat l ion s u mb ore
t h a n t h e s e p e r c e n t a g e s a r e c o n s i a d e dr ifferen e d a ce b et ween s amp les , an d th e s tatis tical
a n a l ys e s a r e p e r f o r m e d w i t h t h i s c o n s i d e r a t i o n i n t h e c u r r e n t p r o j e c . t
2 . 4 . 2 . C 2 o l o r i m e t e r
T h e c o l o r i m e t e r i s a n a p p a r a t u s t h a t a l lo ws th e ab s orb an ce of li gh t at a p arti cu lar w a v e -
len gth or f r e q u e n c y lour) ( c o o f vi s u al li g h t to b e d etermin ed . Dif feren t ch emi cal s u b s tan ces
ab s orb var yi n g f req u en ci es of th e vis ib le s p ectru m. C olo ri mete rs rel y on th e p rin cip le th at th e
a b s o r b a n c e o f a s u b s t a n c e i s p r o p o r t i o n a l t o i t s c o n c e n t r a t i o n , i . e . a m o olu r e tion c o n c e n t r a t e d s
gives a h i gh er ab s orb an ce r ead in g.
A q u an t i t at i ve r ead i n g f or t h e c on cen tration of a s u b s tan ce can b e fou n d b y makin g u p a
s eries of s ol u t i on s of kn own c on cen tratio n of th e ch emical u n d er s tu d y, an d p lottin g a grap h o f

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
a b s o r b a n c e a g a i n s t c o n c e tion n t r . a B y r ea d in g th e ab s orb an ce of th e s p ecimen s u b s tan ce on th e
grap h , a val u e f or i t s c on cen tration is f ou n d .
M e t h o d o f t h n e z y e m e l i n k e d i m -s m o u r n b o a n t a s s a y ( E L I S A ) [ V o l l e r , 1 9 7 8 ]
T h e E L I S A i s i d e a l l y s u i t e d t o a s s a y i n g p r o t e i n f a s c t b o ur t can s e . b e g . ad ap h o tr ed m o n e
to me as u re s mal l mol e cu l es as well. In t h e c u r r e n t p r o j e c t, v ariou s c om merciall y a vailab le
E L I S A k i t [iDS s U. K. , h t t p :/ / w w w . i d s l t d . c o m /] a n d C y t o T o x ® 9 6 [P rome ga U . K.,
h t t p :/ / w w w . p r o m e g a . c o m /] were p u rch as ed an d u s ed for meas u remen ts of th e h o r mon e le vels
an d LD H l e vel s t o d et er mi n e th es e con ce n tration s .
2 . 4 . 3
M e t h o d s in vitro [S e e a l s o A p p e n 4. d i f o x r d e t a i l e d p r o c e d u r e s ]
2 . 4 . 3 1 P r e p a r a t n i o f t i s s u e c u l t m u r f or e cel m e l d cu i lu tu re i n v i t r o
T i s s u e c u ( T l C M t ) wa u s r u s e d f o m r i n e c u d b a i t i o n u o m f c e l l s i n t h e p r o j e c t. It c o n s is ts
of R P M I 1 6 4 0 s up p l emen t ed with 1 % glu tamin e (2 0 0 mM), 1 % p en icillin (5 00 0 IU/ml)/
s t r e p t o m y c i n ( 5 0 0 0 m c g / m l ) , 1 % H e p e s -es sb en u f ti f al e ami r , n o 1 % aci dn s o (1 n 0 0 x), 1 %
s od iu m p yru vat e (1 0 0 mM).
Co r t i s o l l e l v in th e t i s s u e c u l t u r e m e d i u m
In ord er t o s u p p l y es s en t i al n u trition for c ell cu ltu re, 1 0 % Fetal C al f Seru m ( FC S :
S i g m a ® ) w a s a d d e d ( T C i M n ) wh en t cel i ls s were s u in cu e b ated c i u n l v i t . t r u o r e m e d i u m
E LI S A a s s a ys s h o w t h a t t h e t i s s u e c u l t u r e m e d i u m c o n tai n in g 1 0 % FC S con tain s 5 .9 n M
c o r t i s o l ; a n d t h i s w s m a s a l l i n c o m p a r i s o n t o t h e a m o u n t o f c o r t i s o l in f o th u e n d 3 4 i n p l a s m a
volu n teers (2 9 .5 - 265 . 8 n M ; m e a n 1 3 1 . 8 , S D = 5 0 [Fi . 3 ) gu re 1 1 ].
3 0 0
2 5 0
2 0 0
1 5 0
1 0 0
5 0
0
F i g u r e 1 1: I n d i v i d u a l c o r t i s o l l e v e l s i n t h e t i s s u e c u l t u r e m e d i u
m ( l e f t : 5 . 9 n M )
an d in p l as ma from 3 4 vol u n teers ( righ t : 2 9 .5 - 265 . 8 n M)
P h . D . a t U n i v e r s i t y o f L o n d o n - 6 9 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
C o n c l u s i o n :
Th e l e v e l o f c o r t i s o l i T n was C t M h e low , an d th ereaft er in th is th es is , TC M on l y was
con s id ered to b e c o r t i s o l e. f r e
2 .4 .3 .2 N K c y t o t o x i c a c t m i e a v i s u t r y e d f b y l o w to metr c y y [ G o d o y-R a m i r e z e t a l . , 2 0 0 0 ]
De t a i l e d p r o c e d u r are e s giv en in th e Ap p en d ix 4 .
E ffect or cel l s (P B M Cs ):
P e r i p h e r a l v e n o u s s b a l m o p o l s d e w e r e c o l l ue s in c t g e Vacu d tai n ers [Bect on Dickin s on ,
Oxf ord , U. K.]. Hep ari n i zed b lood was c e n trifu ged (1 5 0 0 rp m for 1 0 min u tes at r oo m
temp erat u re). Th e p l as ma w as re mo ved a n d th e b lood p ell et recon s titu ted b y th e a d d ition of
R P M I 1 6 4 0 . T h i s w t a h e n m i x e d a n d o v e to r Lymp l a i d h op o n rep . P B MC were rec ove red fr om
th e in terface aft e r cen t ri fu gi n g (1 5 0 0 rp m) f or 3 0 min s at r oo m te mp eratu re [ B o y u m , 1 9 7 4 ].
Viab ilit y was as s es s ed an d ad ju s ted b y d ye ( Eos in 0 .0 5 % ) exclu s ion .
Th e s ep arat ed effect or cel ls (P BMC s ) b y L y m p h o P r e ® p were was h ed twi ce an d
s u s p e n ded in th e TC M ; t h 1e 0 n l o f a n t i-h u man C D4 5 mon ocl on al an tib od y d irec tl y
c o n j u g a t e d w i t h f l u o r e s c e i n i ns at o t e h ( FITC i o c y a ) was ad d ed an d i n c u b a t e d f o r minut 2 0 e s.
T h e s e c e l l s w e r e w a s h e d after a g a i th n e , las t a was n d h , con cen tration of cells was as s es s ed b y
6
cou n tin g cel ls wi th d y e e x c l u s , i o a n d t h e c e l l c o n c e n t r a t i o n a d j c u e s l t l / s e ml d bt y o 5 x 1 0
ad d in g TC M p r i o r t o m i x i n g w i t h t a r g , e t i c e . l e l . s K 5 6 2 c e l l s , f o r . t h e N K C A a s s a y
T a r g e t 5 6 2 c e l l l i n l e ) : s ( K
K5 6 2 h aemat op oi et ic tu mou r c ells s erv ed as th e target cell f o r d e t e r ing m i Nn K c yt ot o xi c
a c t i v . i t K y 5 6 2 c e l l s a r e e a r y t h u h m r o a m n y e l o c y t i c l e u k a cell e m i lin a e, wh ich ma y tran s fo rm if
a l l o w e to d o v e r g r o w r e s u l t i n g i n l o s i n g t h e i r s e n s i t i v i ty t o b e -cells k i . l Hen l ce, e td h e b y N K
K5 6 2 cel l l i n e s h ou l d b e ren ewed ever y o n e to two m on th s , b y s tartin g with a n ew b atch of
frozen c el l s fr om t h e l i q u i d n itrogen freez er.
In o r d e r t o m a i n t a i n a r e a d y s u p p l y o f c e l l s i n t h e o p t i m a l g r o w t h p h a s e f o r h e t N KC A
a s s a y , o p t i m a l d u r a t i o n a n d c o n c e n t r a t i o n o f K 5 6 2 c e l l s d u r i n g c e l l c u l t u r e
d e t e r m ing i n th e gr owt h ch aract e ri s ti cs of th is cell lin e.
P h . D . a t U n i v e r s i t y o f L o n d o n - 7 0 - I m p e r i a l o C n o d l o n l e g e L

Cell numbers per mL (in Log-scale)
P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
G row th ch a ra cteri s ti cs of K 5 6 2 cell line u s e d a s t a r g e t s f o r a s s e s s i n
K5 6 2 cel ls s h ou ld b e i n t h e l o g a r i t h m i c g r o w fo t r h p e t h a s e u s e o as sf a y, as N cel K C ls A
i n t h e e a r l y ( d e v e l o p i n g ) a n d l a t e ( s a t o u f r t a h t e i e r d ) e v p e h l o a p s m e e n t ar e res is ta n t to killin g.
K5 6 2 cel ls (r e c o v e r e d f r o m f s a r m o p z l e n ) w e r e c u l t u r t e v d a r a i o u s s e e d i n g c o n c e n t r a tion s of
4 5 6
1 . 5 x , 1 0 1 . 5 x a 1 n 0 d 1 . 0 x c e 1 l 0 l ps er ml in 1 0 ml fl as ks wi th tis s u e cu ltu re m ed iu m, an d
o
each f l a s k w a s p l a c e d C a t i 3 7 n a 2 h u mid 5 % ifi ed C in O cu b at or fo r 3 d a ys . Th e K5 6 2 viab le
cell con cen t rat i on i n each fl as k w as as s es s ed on Da y 0 , 1 , 2 , an d 3 an d s imu ltan eou s l y th e
p e r c e n t a g e o f d e a d c e l l s w [ a Figu s m re e 1 a 2 s ]. u r e d
1 00 00 00 0 0
1 0 00 00 0 0
1 00 00 0 0
10 00 0 0
1 00 0 0
F i g u r e 12a: T h e g r o w t h r a t e c u r v e o f K 5 6 2 c e Fi l l gu s r e 12b: T h e de a d c e l l % o f K 5 6 2 c e l l s
( T h e r e d l in i n F e i g u r e b 1 i 2 n d i c ates th e ma ximum a c c ept ab le le ve l of dead K562 cell s)
4 5 6
Fi gur e 12: K5 62 ce ll gr owt h a t s t a r t i n g c e l l c o n c e n t r a , t 1.5x10 i o n s and o f 1.0x10 1 . 5 x 1 0 c e l l per s mL
Fi gu re 1 2 a s h ows th at fr om Day 0 t o 3 , t h e K 5 6 2 c e l l s w -g e rowth r e i pn h as t e h e l o g
r e g a r d l e s s o f s e e d i n g c o n c e n t r a t i o n . T h e t cell h i g h con e s cen trat ion s wer e ob tain ed with a
5
s e e d i n g c o n c e n t r a t i o n o f c e 1 l . l ps 5 er x mL. 1 0 F i g u r e 1 2 b i l l u s t s r th a t at e th e lowes t
5
p e r c e n t a g e d e a d c e l l s w a s o b t a i n e d w i t h a s e e d i n g c o c n e l c l e ps n er t r mL. a t i o n o f 1 . 5 x 1 0
H e n c e , i t c a n c o n b c e l u d e d t h a t t h e c e ls s h ou ld b e p as s ed ever y two t o th ree d a ys a t
5
a p p r o x i m a t e l y 1 . 5 cells x p1 er 0 ml o f c u lt u re in TC M s u p p lemen ted with 1 0 % foetal cal f
s eru m.
K562 growt h curve i n cul t ure
N K C A as s ay proc e du re:
1.5x10^4 cells/ml
1.5x10^5 cells/ml
1.0x10^6 cells/ml
da y0 da y1 da y2 da y3
Dead cell percentages
D e a d K5 6 2 % i n c u l t u r e c o n d i t i o n
Effect or an d target c el ls , i .e. f r e s h P B M C s a n d K 5 6 2 c e l l s , w e r e a d d e d 12 i n d u p l i c a t e
x 7 5 m m r o -b u n otto d m tu b es [Bec k Di c k in s on , Oxf ord , U. K.] t o yield th e Ef fecto r to T arg et
(E :T) rat i o o f 5 0 :1 , 2 5 :1 , 1 2 .5 :1 in 2 0 0 l. C on trol tu b es were s et u p with o n l y ta rg et or effe ctor
cells for d e t e r m ing i n s p o n t a n e o u s c e l l r a d t e a s. t h T u b e ix s ed b y w gen e tl r y te ap p in g, m an d
1 00
80
60
40
20
0
1.5x10^4 cells/ml
1.5x10^5 cells/ml
1.0x10^6 cells/ml
Da y 1 Da y 2 Da y 3
P h . D . a t U n i v e r s i t y o f L o n d o n - 7 1 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
in cu b at ed at 37 °C for t h ree h ou rs (in th e u n ivers it y s tu d en t s tud y) or f ou r h ou rs . After
in cu b at i on , t h e t ub es were p laced on ice u n til an al ys ed . Twen t y mic roliters of p ro p id iu m iod id e
( P I ) , w h i c h s t a i t n h s e n u c l eu s o f d e a d c e l ls , w e r e a d d e d t o e a c -1 h 5 min t u b ue tes 1 b0 efore
acq u is it i on .
F l o w c y t o m e t r i c a c q u i s i t i o n :
Fl ow c yt o met r y was p er for med with a FAC S C alib u r c yt om eter [B e c k D i c k i n ]. s o Th n e
i n s t r u m e n t w a s s e -c t o l f o u r t a w n a o l y s i s u s i n g F A C S c o m p s n o f j t w u a n r e c ith t i n i c o n w
C alib rit e b ead s [B e c k D i c k i n ]. s o D n a t a w e r e c o l l e c t e d i n l i s t m o d e a n d a n a l y s i s w or a s med p e r f
u s in g C el lQu es t s oft ware [B e c k D i c k i n ]. s o A n re gi on was s et on a d ot p lot of SSC vs .
f l u o r e s c e n c e 1 (FL-1 : C D 4 5 ) a r o u n d t h e c l u s t e r o f t a r in g e th t e con c e l trol l s a mp i d e le n t i f i e d
t u b e s a n d p e r c e n t a g e s o f P -s I t a i n e d c e l l n u m b e r
calcu lat ed b y s u b t ract i on of ta rget total fr om in d ivid u al totals [Fi gu re 1 3 ].
i n t h e r e g i C o A n was w e r e c o u n t e d
Fi gur e 13a: K 5 6 2 c e l only l s t ub e a c qu is it ion Fi gu r e 13b: P B M C s o n l y t u b e a c q u i s i t i o n
Fi gu r e 13d: K 5 6 2 h i s t o g r a m b y P I s t a i n i n g
(M 1 : P I s t a i n i n g p o s i t i v e c e l l s )
Fi gur e 13c: t e s t i n g t u b e ( m i x e d w i t h K 5 6 2 a n d P B M C s ) a c q u i s i t i o n
Fi gur e 13: A c q u i s i o n s e t t i n g s f o l o f w t c h yt e o m e te r f o r m e a s u r i n g t h e f l e v e C N l A K s o
A r e gio n s e t t in g ( R1) f or K562 [Figu r e 13a,b] and a p r o c e s s o f d e a d K 5 6 2 [Figur d e t e e c t 13c] i o n
f o l l o we d b y h i s t o gr a m p e r c e nt a ge a na l ys i s ( co u n t in g PI st a ine d ce ll n u mb e rs ) [Figu r e 13d]
P h . D . a t U n i v e r s i t y o f L o n d o n - 7 2 - I m p e r i a l o C n o d l o n l e g e L
M 1

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
P recis ion of le vel s in th e N K c y t o t o x i c a c t m i e v a i s u t r y e d b y fl o w c y t o m e t r y
Meth od ol o gi cal vari at i on i n N K c ytot oxi c activit y was as s es s ed in p relimin ar y b l o od
s a m p l e s f r o m t h r e e v o l u n t e e r s , . an d al T l nh in r e e e s a m p
s amp les were d u p li cat ed to meas u re N K c ytot oxic activit y. Ch a n g e s i n t h v e e l s e o f N K C A
mor e th an t w i c e o f s t a n d a r d d e v i a t % i o k n i s l ) l ( we i 1 . r n e g 4 4 c o n s i d e r e d a o s u t o f t h 9e 5 %
c o n f i d e n t i n t e r v a l. C h an ges in N KC A l e v e l m o r e t h 1 a . n 4 w 4 e r e c on s id ered as a d ifferen ce
b e t w e e n s a m p s l , e a n d r e s u l t s f r o m t h a e l y s t e a s t i w s e t r i e c a e l x a m a n i n e d w i t h t . h i s d e f i n i t i o n
2 .4 .3 .3 N K -ce l l c h a r a c t e r i s t i d c u s r i n g N K C A a s m s e a y s u r e d b y f l o w c y t o m e t r y
E xpr es s ion o f Na t u r a l c y t o t o x i c r e c e p t o r ( N C R m ) e a s u r e d b y f l o w c y t o m e t r y
Ce l l s u r f a s pc erf e or med s t b y a in cu i bn at i n g n with g 5 w l of p articu lar mon oclon al
an tib od i es for 1 5 mi n at r oo m te mp eratu r e in th e d ark. T h e a n a l y s i s o f n a t u r a l c yt o toxic recep to r
(N C R s : N k p 3 0 o r N ) k w p a 4 s 6 p e r f o r m e d u s i n g f o u -c r olo r fl ow c yt o met ri c acq u is ion an d
Flo w J o ® f l o w c y t o m e t r y a n a l y [Figu s e s r e 1 4 ].
FL-3: CD56-CyChrome staining
Whole
lymphocytes
Gated NKC
sample
C D 3 - C D 5 6 +
( N -c K e l l s )
F L -4 : C D -A 3 P C s t a i n i n g
F i g u r e 1 4 : a C D 3 - C D 5 6 + N K -cells in dot plot
N C R s ( + ) %
F L -1 : C D 1 -F 6 I T C s t a i n i n g
Fi gur e 14: Ac quis ion s e tt ings of t h e f l o w c y t o m e t e in r t h e N C R a n a l y s e s
C D 5 6 b r i g h t C D 1 6 -
R e g u l a t -c e o ll s r y N K
C D 5 6 dim C D 1 6 +
C y t o t o -c x e l i l s c N K
F L 2 : N k p 3 0 o r N k -P p 4 E 6 s t a i n i n g F i g u r e 1 : 4 NK-s b ub s et s of C y t o t o x i c a n -c d e l l s R i n e d o g t u p l ot l a t o r y N K
F i g u r e c 1 : 4 P p e r c e n t a g e o f N C R e x p r e s s i o n s
A regi on was s et on a d ot p l ot o f FL-3 (C D5 6 ) vs . FL-4 (C D3 ) to t arg et C D 3 - C D 5 6 + N K -
cells [F i g u r e a], 1 4 an d fu rt h er re gi on s f or N K s u -p b o p u l a t i o n s e w r e d e t e r m in ed b y a d ot p lot of
FL-3: CD56-CyChrome staining
P h . D . a t U n i v e r s i t y o f L o n d o n - 7 3 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
d i m
FL-3 (C D5 6 ) vs . FL-1 ( C D 1 6 ) [Fi gu re 1 4 b : C D 5 6 C D 1 6 + Cyt ot oxi c an d C D 5 6 b r i g h t C D 1 6 -
Re g u l a t -c o e l r l s y u b s e N ]. t s K Th e p ercen tage e xp res s ion s of NC R s were th en me as u red as a
p ercen tage o f FL-2 ( N C R s ) p o s i t i v e c e l l s w i t h i of n a t s el h ect e ed p o re p u gi l oa n t (C i o yt n ot oxic
o r R e g u l -c a e l t l s o ) r h is b y to y gra N m K [Fi gu re 1 4 c : p e r c e n t a g e o f c e l l s N e C x R p r s]. e s s i n g
2 .4 .3 .4 P rol iferat ive res p on s e m e a s u r e d b [ y
3 H ] -t h y m i d i n e i n c o r p o r a t i o n
P B M C c u l t u r e s w i t h s t i m u l u s :
P e r i p h e r a l b l o o d m o n o n u c l e a r c (P e l BMC l s s ) were cu lt u red wi th microb acte rial p rotein
(p u rified p rot ei n d eri vat i ve : P P D) an d Herp es an tigen (me mo r y recall an ti gen s ) f or 6 d a ys in
t i s s u e c u l t u r e m e d i u m ( T C M : c o n t a i n i n g 1 0 % f e t a l calf s e ru m) with /ou t co rtis ol [h yd r oc orti s on e,
S i g m ] a t ® o m e re a s l ymp u h oc yt e p rol ife r at ive res p on s es . In ad d ition , T h r e e d a y c u l t u s r with e 1 )
Staphy l o c o c c a l e n t e r o t o x i n B ( S E B u ) s e d a s a s t i m nt, u l a s u p e r a n t , wh i g ich e n ca n s ti mu lat e
b o t h n a ï v e a n d m e m o r y c ; e l a l n s d 2 ) P h yt oh aema ggl u ti n in A (P HA) ch os en as a mi togen wh ich
s t i m u l a t -cells e s an a d l th ereb l y T a ct s as a p os itive c on trol fo r p roli ferati ve res p on s es .
Whole B loo d C e l l c u l t u r e ws ith s ti mu l us [ H u t c h i n s o n e t a l . , 1 9 9 [See 9 ] al s o Ap p e n d i x 4 ]:
T h e w h o l e b l o o d a s r s meas a y uf ri o n g p r o li ferat iv e res p on s es was ap p lied in ord er t o
red u ce cel l h an d l i n g an d man ipu lation . In b rief, wh ole b lood (d ilu ted 1 /4 ) was in cub ated for 3
d a ys wi th 1 2 .5 g / m l o f SE B, s u p e r-a n t i g , e or n 1 2 .5 g/ ml of P H A, m i t o , g to e n m eas u re
l ym p h o c yt e p r o li f e r a t i v e r e s p o n . s e Ps HA or S E B were in cu b at ed with 1 :1 0 d ilu ted b lood with
o r w i t h o u t 2 5 0 -s h a n p e M d w c e l o l r p s l t in a t i tot e s al o am l ou n t of i 2n 0 0 9 L, 6 a n d in U cub ated
0 , 2 4 a n d 4 8 h o u r s f ol l o w e d t b h y e [ 3 H ] -t h ymi d in e in corp orati on as s a y.
[ 3 H ] -t h y m i d e i n i n c o r p o r a t i o n
T h e p l a t e s w e r e i n n c a u b 2 ha 5 u mid t % e ifi d C ed O at a mos t p h3 ere, 7 ° an C d th e cells were
p u ls ed wi th 1 C i t r i t i u m [ m e h yl- 3 H ] T h y m i d i n e ( [
3 H ] -T d R ) p er w e l l f o r las t h t e f ou r h ou rs o f
in cu b at ion . Th e s u p ern at an ts were h arves ted u s in g a S k a t n r AS o Har ves ti n g s ys te m [S h atr on ,
3
S u f f o l ] k a n d t h e a m o u n t o f H] [ in corp o r at ed wi th th e cells d etermin ed on a Walla c 1 2 0 5 Liq u id
scintillati on C ou n ter [P h a r m a c i a , B e c ]. k s R es u lt s were p res en ted as cou ts p er min u tes (cp m).
P h . D . a t U n i v e r s i t y o f L o n d o n - 7 4 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
2 .4 .3 .5 T-ce l l c h a r a c t e r i s t i c s te a f r i n v i t i r n o c u b a t i o n m e a s u r e d b y f l o w c y t o m e t r y
C e l l p r e p a r a t i o n f o r p r o l i f e r a t i o n a n a l y s e s
5
P r e v i o u s l y t i t r a t e d c o n c e n t r a t i o n o f P P D o r H e r p e s a n t i g e n w a s i n c u b a t e d
cells p e r m L P B M C s in total a mou n t o f 1 .2 m L p e r w e l l 2 4 i wel n l cu lt u re p l a t e s /ou w i t 2h 50
n M c o r t i s o l. 1 2 .5 g / m L o f P H A o r S E B w e r e i n c u 1 b : a 1 t 0 e d i w l i u t h e d b l /ou o o t d 2 50 w i t h
n M cort is ol in 2 4 -s hU ap ed w e l l p l s a in t e tot al a mou n t 1 .2 m L, an d in cu b ated f o r 0 , 2 a 4 n d 4 8
h ou rs . T h e p l a t e s w e r e i n c 2 u h u b m i a d t i f e i e d a t a m o t s p a h n e d 3 r , e th 7 e n ° cel C ls i n a 5 % C
were a l l o c a t d e i n t FAC o S 1 2 x 7 5 r ou n d b ot tom tu b es [Bec k Dic kin s on , Ox ford , U. K.] b ef ore
f o l l o w i n g p r o c e d u . r e s
S t a i n i n g c e l l s u r f a c e m a r k e u r p s o n T-l y m p h o c y t e -p s o p u b l a t i s o n
Ce l l s u r f a s p c e r e f o r m e s d t b y a in cu i bn at i n g n with g 5 w l of p articu lar mon oclon al
a n t i b o d i e s f o r 1 5 m i n a t r o o m t e m p e r a t wh u r ol e e bi ln o od t as h e s a y, d a er r yt k . h roc I ytes n
were l ys ed for 2 0 mi n wi th 1 ml of 1 0 x d ilu ted l ys in g s ol u tion [B e c t o n D i c k i ] n in s o th n e d ark.
I n b o t h m e t h o d s , c e l l s w e r e w a s times h e d wi t h tr h e te h e TC M an d fi xed in 1 0 0 l of 4 % o f
p a r a-f o r m a l d e h y d e i n P B S ( f i x a . t i o n b u f f e r ) f o r 2 0 m i n
E x p r e s s i o n o f C D 2 5 -l y o m r p h o C c y D t 9 e 5 s m u e p a s o u n r e d T b y f l o w c y t o m e t r y
C e l l s a m p l e s w e r e r u n o n a F A C S C a l i b u r f l o w c y t o m ) e an t d e r ( B e c t o n D i c k i n s o
an al ys ed b y C el lQu es t s o ft ware . C D 3 -C y -C h r o m e ( -3 F L ) a n d C D -A 8 P C ( -4 F L ) fl u ores cen t
c o n j u g a t e d a n t i b o d i e s w e r e u s e d t o l a b -p e l o p u l y a t m i p o h n o ( s c C y D t 3 e s u b
+ C D 8 + T-c e l l s an d
C D 3 + C D 8 - +
T-c e l l s a s C D T-c 4 e l l s ). At l e a s t 5 0 0 0 e v e n t s i n t h e l i g h t-s c a t t e r ( FSC /SS C )
l ymp h oc yt e re gi on we re acq u ired . E a c h ly m p h o c y t e s -p u o b p u l a t i o n a w s i d e n t i f bi y e a d g a t e on
FL-3 vers u s FL-4 d o t p l o t s , -C i . D e 8 . s c a C t D t e 3 r d o t p . l T o t h s e F -f I l u T o C r e s c e n c e i n t e n s i t i e s
(FL-1 ) o f C D o2 r 5 C D 9 5 -l ab el led l ymp h oc yte p op u lation s an d is ot yp e c on trol s w ere d is p la yed
a n d d e t e r m i n e d a s m e a n c h a n n e l v a l u e s o n a -d f o e u c r a d e l o g s c a l e i n h i s t o g r a m . p l o t s
T h e r e l a t i v e q u a n t i t oy r Co D9 f 5 C exp D 2 5 res s ion was calcu lated b y th e p ercen ta ge o f
c e l l n u m b e r s i n t h e p o s i t i v e i n t e n s i t y n flu a r or e a es , cen a n ce d im n te en a s it y (m. f.i. ) was
c a l c u l a t e d a s t h e d i f f e r e n c e b e t w e e n m e oa r n C D9 v a 5 l an u e d s is ot o f yp e C cD on 2 t5 rol lab elled
T M
s a m p l e s . T h e i n s t r u m e n t c a l i b r a t i o n w a s p e r f o r m e d b y C e l l
b ead s .
P h . D . a t U n i v e r s i t y o f L o n d o n - 7 5 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
E xpr es s ion o f Annexin V- PI o n -l y T m p h o c y t e s m e a s u r e d b y f l o w c y t o m e t r y
Th e A n n -F e I x i T C n ( -1 F L ) V a n t i b o d y & p r o p i d i u m i o d i n e : ( P I -3) F L s tai n in g met h od for
d etecti on of ap op tos is was u s ed to d eter m in e th e effect of c ortis ol u p o n a p o p t o t i c p r o c e s . s e s
Fo u r -c o l o r f l o w c y t o m e t i r s i c o n a c q lo a u n w d J o ® F f l o w c y t o m e t r y a n a l y s w e e s r e p e r f o . r A m e d
r e g i o n w a s et on a d ot p lot of SS C vs . FL-2 ( C D -P 3 E ) t o t -l a ymp r g he oc t yt es T , a n d fu rt h er
p e r c e n t a g e s o f n e c r o t i c c e l l s , a p o p t o t i c c e l l s a n d l i v e d c e bl y l a s d ow t e pr lot e of d e FL- t e r m i n e
3 (P I) vs . FL-1 ( An n exi n V) [Figu re 1 5 ].
Side Scatter (SSC)
W h o l e l y mp h o cytes
F L -2 : C D 3 s t a i n i n g
F L -3 : P I s t a i n i n g
Fi gur e 15b: s e t t -up i n a g re gio n f or a popt ot ic c e lls
u s i n g n e ga t i ve i s o t yp e c o nt r o l i n a d ot p l o t
Fi gur e 15: Ac quis ion s e tt ings of the f l o w c yt o m e ter i n t Annexin h e V- P I a n a l y s i s
A regi on was s et on a d ot p lot o f FL-2 ( 3) C vs D . SSC t o tar get T-cells ( F i g u r e a ) fr 1 om 5
w h o l e l ym p h o c yt e s g a te d b y t -S C h C e p l F o S t C p r e v i , an o u d s fu l y rt h er r e g i o n s f o r a p o p t o t i c
cell s u bs e t s e w r e d etermi n ed b y a d ot p lo t of FL-3 (P I ) vs . FL-1 (A n n e x ) i ( Fig n u re V 1 5 c:
FL-1: Annexin V staining FL-1: Annexin V staining
( g a t e d b -S y S C t p l o h t ) e F S C
T-l y m p h o c y t e s
Fi gur e 15a: a r e g i -c o e n l l s i f n a o d r ot p T l ot
Ne gati ve c ont r ol
( f o r g a t i n g p u r p o s e )
Apopt ot i c
c e l l s
L i v e c e l l s
Apopt ot i c
cel l s
L i v e c e l l s
N e c r o t i c c e l l s
E x p e r i m e n t s a m p l e s
N e c r o t i c c e l l s
F L -3 : P I s t a i n i n g
F i gur e 15c: a r e gi o n f o r a p op t ot i c ce l l s i n a do t p l o t
+ - +
ap op tot ic ( A n n e x & i P n I ) a n V d n e c r o t i c c e l l ( P ) I s u b s et s i n t -l h y e m p h T o c y t e s ). F i g u r b e 1 5
s ho w s t h e m e t h o d -u s e p t for t i th n e g re gi o n of ap op tot ic cells b y u s in g n egati ve is ot yp e con tr ols .
P h . D . a t U n i v e r s i t y o f L o n d o n - 7 6 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
2.5 S t a t i s t i n c a l ys e s a
All p s ych ol o gi cal an d p h ys iol o gical lab o r ator y s amp les we re a n o n ym i s e an d d p roc es s ed
u s i n g a n a ss ign ed s tud y n u m b e r to e n s u r that e t h e a n a l y s e ws ere p e r f o r m e d b l i n terms d l y of i n
t h e g r o u p s a s n u d b gr o u ps t w o h i c h t h e s a m s p b l e l o n g . t o
T o e x a m i n e t h a e p r i o r i h yp ot h es is th at p s ych olo gical in ter ven tion ma y c ou n teract th e
d e t r i m e n t a l e f f e c t o f s t r e s s o n w e l l-b e i n g , -t o r e n a t m e n t a n a l ys is (a n a l ys i s of res u lts fr om on l y
th os e wh o co mp let ed th e tri al) was p erf or med . W h e n statistical d i f f e r e es n c w e r e f o u n d in th e
p r i m a r y o u t c o m e m e a s in u r u e n i v a r i a t a e n a l y s e s , I n -t t e o-t n r t e i a t o n a n a l y s w i s a s p e r f o r m in e d
o r d e r t o c o n f i r m t h e r e s u l t s . T h e i n te n t i o -t n o-t reat is th e an al ys is of res u lts fro m e v er y s u b ject
en rolled i n t h e t ri al re gard l es s o f wh eth er th e y co mp leted th e trial, an d all in d ivid u al s wh o
w i t h d r e w w e r e c o u n t e d i n t h e n u m b e r o f s u b jects wh o failed th e h yp oth es is .
Un i v a r i a t s t e a t i s t i c a l an a l y s e s w e r e r m p e r d f t o t e s t s p e c i f i c h y p o t s h t a e t s e d s a t each
p o i n t i n t h e r e s u l t s s e c t io n [3 .1 a n d 3 . 2 i n v i sv tu o d ies ; an d 3 .3 an d 3 .4 in vir to e x p e r i m e n t s].
S a m p l e s i s z of e each grou p were rel at i vel y s mall in th e i n v i an v o al ys es [3 .1 an d 3 .2 ], an d
t h e r e f o re e s s e n t i a l l y m u l t i v s a e r s i a t r e a u n a l i t y ach k o e l ie y ve mean in gfu l res u lt s . If
mu ltivari at e an al ys es were p erf or med , s t a n d a rd e r r o r s w o u l d b e r e l h a givi t i nv g e ver l y y h wi i dg e
9 5 % c o n f i d e n ti a l i n t e r v a ls (C . I.) in d icating a l ot of u n certain t y in fin d in gs . Fo r th is reas on , it
was felt i n a p p r o p r i a t o e p erf or m mu lt iv a ri at e an al ys es .
Th e S t a t i s t i c a l P a c k a g e o f S o c i a l S c i e n c e v e r s i o n 1 1 . 0 ( S P [ S F S i e ® l ) d , 2 0 0 3 ] was u s ed
with a p val u e o f les s th an 0 .0 5 con s id ered as a s t a t i s t i c a l l y s i g n i f i , c an a n d t a v p a val l u e u e o f
l e s s t h a n 0 . 1 0 a s h a e S tu s d y t Sa ize t i Det s er t mi i nc at a ion l (SSD) t r pe ro n gra d . mm e T [ Leh man n ,
2 0 0 1 ] w a s u s e d f o r amp s le s ize cal cu lat io n a t t h e 5 % s i g n i pf ower. i c a n c e
Fo r in d ep en d en t n ormal l y d i s trib u ted d ata, a n a l y s e s o f v a ri a n c e ( A N O V A ) w e r e p e r f o r m e d
f o l l o w e d b y p o s t-h o c St u d en t t-t e s t e p s e a . t e -meas d R u res AN O V A w a s u s e d f o r l o n g i t u d i n a l
d a t a n ormal l y d is tri b u ted [ T a b a c h n i c k & F i d e l l , 1 9 9 . 6 For ] n o n-n o rmal l y d i s t r i b u dt ata, e d
r e p e a t -m e d e a s u r e A N O V A f o l l o w e d b y 1t 0 h % e tri mmi n g m et h od [ W i l c o x , 1 9 9 7 ]
p e r f o r m e trim d mi . n g met T h od h we as ap 1 p li ed 0 in % ord er to r em ove o u t l iers s o t h at th e
ANO V A m et h od can b e ap p lied . T o c o n f i r m t h e f i n d i n g f r A o m N O t V h A e f i o n g l th e l 1 0 o % w
trimmi n g met h od , t h e N -p o n a r a m e t r i c A N O V A th ( e K r u s k a l -Wallis r a n k t e s ) t wa s s u s e d
[ T a b a c h n i c k & F i d e l l , 1 9 9 . 6 ] T h e W i l c o x o n r a n k t e s t s w e r e u s e d n-n f or o mal r p l y a i r e d a n d n o
d is trib u ted d at a [ A j e t u n m o b i , 2 0 0 2 .
]
P h . D . a t U n i v e r s i t y o f L o n d o n - 7 7 - I m p e r i a l o C n o d l o n l e g e L
a w s

Chapter II I
Results
- 7 8 -

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
CO NTENTS O F CH APTER 3
R e s u l t s
3. 1 Th e i n flu en c e of p s yc h o l o g i c a l i n t e r v e n t i o n u p o n s -rela t r e s s t ed ch an ges i n
u n i v e r s i t y s t u d e n t s f a c i n g a c a d e m i c e x a m i . n a t i o n s
3.1. 1 V a l i d a t i o n o f a c a d e m i c e x a m i n a t i o n a s a s t r e s s i n d u c e r f o r u n i v e r s 83 i t y s t u d e n t s
3.1. 1. 1 Im p a c t o f a c a d e m i c e x a m pi on n a pt s ych i o n ol ou gi cal meas u res o f
s t r e s s a n d a n x i e t y
3.1. 1. 2 Imp act o f acad e mi c e xamin ation u p on i m m u n e p a r a m e t e r s
3.1.2 D i f f e r e n c e s in th e le vel s o f l ym p h oc yt e s u b s ets and NK c ytot oxic act ivit y
( N K C A ) b et ween u n ivers it y s tu d en ts w i t h h i g p e h rc e i v a e d n s d t r e s s l e v o e l w s 85
3.1.2 . 1 D i f f e r e n c i e n t h e p e r -cells c e an n d t th e a level g e s of No K f N K
c y t o t o x i c a c t i v i t y ( N K C A b etween ) u n iv ers it y s tu d en ts with h igh
a n d l o w p e r c e i v e d s t r e s s l e v e l s
3.1.2 . 2 D i f f e r e n c i e n t h e p e r c -cells e n t b a e g t w e e e n o f u n i rs T v it e y s tu d en ts w i t h h i g h a n d l o w p e r c e i v e d s t r e s s l e v e l s
3 . 1.3 T h e in fl u en ce of p s ych ol ogical i n t e r v e n t u i p o n s t r e -rel s s ated ch an ges in u n i v e r s i t y s t u d e n t s f a c i n g a c a d e m i c e x a m i n a t i o n s
3.1.3 .1 E f f e c t o f p s y c h o l o g i c a l i n t e r v e n t i o n u p o n s t r e s s cep p e tion r in u n ivers i t y s t u d e n t s a n t i c i p a t i n g a c a d e m i c e x a m i n a t i o n s
3.1.3 .2 E f f e c t o f p s y c h o l o g i c a l i n t e r v e n t i o n u p o -related n s t r e s s
l y m p h o c y t e -p s u op b u lat ion s in u n ivers it y s t u d e n t s anticip atin g
a c a d e m i c e x a m i n a t i o n s
3.2 T h e i n f l u e n c e o f p s y c h o a l o g i c n t e r v e n t i o n u p o n p e r c e i v e d s t -o r f -e
s s a n d q u a l i t
l i f e a n d v a r i o u s i m m u n o l o g i c a -a l s d i s e o a s c e i a t e d p -i n a fec r ted a m e t e r s i n
i n d i v i d u a l s
3 . 2.1 D i s e a s e-a s s o c i a t e d a n d s t r -r e s s e l a t e d c -in h fected a n g in e d is vi d u al i s i n H I V
p s ych ol og y i m m u n o l o g i c a l p a r am e t e r s 102
3.2.1 .1 P s y c h o l o g i c a l -in p fecte r o d if n d i ivi l d u als e s recru o it ed f t h e H I V
into the s t u d y
3.2 .1 .2 S t r e s s-r e l a t e d p e r c e p t i d o i n s a n e d a s e p r o g r e -s
s i o n m a r k e r s
i n f e c t i o n
P h . D . a t U n i v e r s i t y o f L o n d o n - 7 9 - I m p e r i a l o C n o d l o n l e g e L
83
84
86
91
93
95
103
110
93

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
3 . 2.2 Th e in fl u en ce of p s yc h o l o g i c a l i n t e r v e n t i o n u p o n d i p s r e a o r s g e s s i o n
p a r a m e t e -in r fected s i n dn ivi d u al H s I (r V an d omis ed con trolled trial f or fou r
m o n t h s p e r i o d ) 117
3.2.2.1 Effect of p s yc h o l o g i c a l in ter ven tion u p on p erceived s tres s an d
a n x i e t -i y n f e c i t e n d i n d H i I v i V d u a l s
3.2.2 .2 Effect of p s yc h o l o g i c a l int e r v e n t i o n u -cell p o n c ou nC ts D i4 n T
H I V-i n f e c t e d i n d i v i d u a l s
3.2.2.3 Effect of p s yc h o l o g i c a l in ter ven tion u p on oth er i mmu n olo gical
m a r k e r s ( -t l r a o n g s f o r m e d v i r a l l o a d l a e v n e l d s -c e N l l K c o u n t s ) in
H I V-i n f e c t e d i n d i v i d u a l s
3.2 .3 T h e i n f l u e n f c p e s y c o h o l o g i c l a in terven ti on u p on d is eas e p rogres s ion m ark er,
C D 4 -c T e l l s -in , fected i n in d ivi H d uI al V s (cas e con tr olled s tu d y o ver 2 4
m o n t h s p e r i o d ) 122
3 . 2 . 3 . 1 A n a l y s i s o f b a s e l i n e d i f f e r e n c e s b e -cell t w e e n t h e t h r
c o u n t 122
3.2 .3 .2 An al ys is o f t h e r a t e o f -c c e l h l a c o n u g n t e ( C i D 4 n g r a C d D i e 4 n t 123 ) T
3.3 In vi t ro i n vesti ga ti on i nt o th e effec t of exp osu re t o st ress h ormon es up on
N a t u r a l K i l l e r c e l l s
3 . 3.1 D e v e l o p m e n t a n d o p t i m i s a t ion o f a flow c yto met ric meth od f o r meas u rin g
N K C A 128
3.3.1 . 1 N K C A a f t e r i n c u b a t i o n o f P B M C s f o r 2 4 h o u r s
3.3.1 .2 N K -c e l l p e r c e n t a g e i n P B M C s a f t e r 2 4 h o u r s i 129 n c u b a t i o n
3 . 3 . 1 . 3 N KC A a f t e r 2 4 h r s i n c u b a t i o n o f P B M C s w i t h c o r t i s o l 131
3.3.1 .4 N K -c e l l p e r c e n t a g e i n P B M C s a f t 2 e r 4 h o u r s ith i n c u b a t i o n w
c o r t i s o l 132
3 . 3.2 C o m p a r i s o n o f t w o m e t h o d s f o r m e a s u r i n g N K c y t o t o x i c a c t i v i t y ( N : K - C A )
3 . 3 . 3
t h e f l o w c y t o m e t r i c m e t h o d a n d t h e c o ( l C o y r t o i T m o x e 9 t 6 r ® i ) c m e t 133 h o d
I n v e s t i g -cell a t pi rofi o les n a n d o f N K C N (c A K o l o r i m e t r i c ) m e t h o d 134
3 . 3 . 3 . 1 NKC A, as s es s ed b y c ol orim etric meth od , after in cu b ation o f
P B M C s f o r 2 4 h o u r s
P h . D . a t U n i v e r s i t y o f L o n d o n - 8 0 - I m p e r i a l o C n o d l o n l e g e L
117
119
121
128
134

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
3 .3 .3 .2 R e p e a t a s s e -cell s s p ercen m e tn ag t e an d o exami f n ation N K of N K
s u b p o p u l a t i o n s i n P B M C s a f t e r 2 4 h o u r s i n c u b a 135 t i o n
3 .3 .3 .3 E x p r e s s i o n o f N a t u r a l C y t o t o x i c R e c (Nkp e p t o r 4s 6 an d Nkp 3 0 ) b y
c y t o t o -c x e l i l c s ( -C C N D K 3 5 6 d i m C D 1 6 + ) p r e a n d p o s t 2 4 h o u r s
i n c u b a t i o n
3 .3 .3 .4 NKC A, as s es s ed b y c ol orim etric meth od , after 2 4 h ou rs in cu b ation
o f P B M C s w i t h 2 5 0 n M c o r t i s o l 138
3 .3 .3 .5 N K C A l e v e l s b e t w e e n p r e a n d p o s cu t b ation 2 4 h wi o u th r or s i n
w i t h o u t 2 5 0 n M c o r t i s o l 139
3 .3 .3 .6 C D 5 6 -cell N K s u b s et p rofi les in P BMC s after 2 4 h ou rs in cu b ation
w i t h 2 5 0 n M c o r t i s o l 141
3 .3 .3 .7 Exp res s i on o f Natu ral C ytot oxic R ecep to rs (Nkp 4 6 an d Nkp 3 0 ) b y
- +
c y t o t o x i c N -c K e l l s ( C D 5 3 6 d i m C D 1 6 ) a f t e r 2 4 h ou rs
i n c u b a t i o n w i t h o r w i t h o u t 2 5 0 n M c o r t i s o l 142
3 .3 .3 .8 N k p 4 6 e x p r e s s i o -cells n po re n an d pc os y t 2t 4 ho ou t rs o x i c N K
i n c u b a t i o n w i t h o r w i t h o u t 2 5 0 n M c o r t i s o l 143
3 .3 .3 .9 N K C A a n d N k p 4 6 e x p r e s -cells s i p re o an n d p os o t n c y t o t o x i c N
2 4 h o u r s i n c u t i b o a n w i t h o r w i t h o u t 2 5 0 n M c o r t i s o l 144
3 .3 .4 E n d o g e n o u s s t r e s s h o r m l o e n v e ls a n d N K C A ( c o l o r i m e t r i c m e t h o d )
3 .3 .4. 1 E n d o g e n o u s h o r m o n e l e v e l s a n d N KC A a t T i m e 0 p o i n t
3 .3 .4.2 En d ogen ou s h orm on es levels an d th e in creas ed levels o f N KC A
a f t e r 4 h ou 2 rs in vi tr o in cu b at ion of P B M C s with ou t exo gen ou s
c o r t i s o l 146
3.4 In vi t ro i n vesti ga ti on i nt o th e effec t of exp osu re t o st ress h ormon es up on
T-l y m p h o c y t e s
3 . 4.1 T-l y m p h o c y t e p r o l i f e r a t i v e r e s p o n s e s a g a i n s t c o m m o n a n t i g e n s
3.4.1 . 1 T-l y m p h o c y t e p r olife rat ion a ft er in cu b at ion of P BMC s fo r s ix d a ys
w i t h a n d w i t h o u t e x o g e n o u s c o r t i s o l 152
3.4.1 . 2 T-l ymp h oc yte p r olife rative res p on s e ag ain s t p u rified p rotein
d erivati ve (P P D) aft er i n cu b ation of P BM C s for s i x d a ys with or
w i t h o u t e x o g e n o u s c o r t i s o l 153
P h . D . a t U n i v e r s i t y o f L o n d o n - 8 1 - I m p e r i a l o C n o d l o n l e g e L
136
146
145
151

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
3.4.1 . 3 T-l ymp h oc yte p r olife rative res p on s e ag ain s t Herp es an tigen aft er
in cu b at i on of P BMC s for s i x d a ys with a n d with ou t exogen ou s
c o r t i s o l 154
3 . 4.2 T-l y m p h o c y t e p r o l i f e r a t i v e r e s p o n s e s a g a i n s t s u -a p e n r t i g e n a n d m i t o g e n 155
3.4.2 . 1 T-l y m p h o c y t e r olife p rat ive res p on s es aga in s t s tap h yl ococ cal
en terot o xi n B (S E B) aft e r i n cu b ation of d ilu ted wh ole b lood fo r
t h r e e d a ys w i t h o r w i t h o u t e x o g e n o u s c o r t i s o l 156
3.4.2 . 2 T-l ymp h oc yte p r olife rative res p on s es aga in s t p h yt oh aema gglu tin in
A ( P H A) a f t e r i n c u b a t ion of d ilu ted wh ole b lood f or th ree d a ys
w i t h o r w i t h o u t e x o g e n o u s c o r t i s o l 157
3 . 4.3 C e l l s u r f a c e m n a r p k r o e l r i f s e r a t o in g T-l y m p h o c y t s e f ollo wi n g s ti mu lat ion w i t h P H A
3.4.3 . 1 E x p r e s s i o n o f a n a p o p t o s i s ( C D 9 5 : - F a s ) c e l l s u r f
l y m p h o c yt es i n v i t r d o u r i -in n dg u ced P pH rol A iferat i on wi th an d
w i t h o u t e x o g e n o u s c o r t i s o l 158
3.4.3 . 2 E x p r e s s i o n o f c e l l-s u r f a c e A n n e -V x i an n d c yt op las mi c P rop id iu m
i o d i n e ( -l P ymp I ) h o c yt i es n a ft T er in cu b at ion with P HA f or th ree
d a ys w i t h o r w i t h o u t c o r t i s o l 163
3 . 4 . 3 . 3 E x p r e s s i o n o f a n a c -2 t i re cv ep a t or ) i ce o ll n s urf ( a ce C D ma 2 5 r ker : I L
byT-l y m p h o c y t e s -induc d eu d pr r oi life n r at g ion wit P H h A a nd wit ho ut e x o ge n o u s c or t i s o l 164
P h . D . a t U n i v e r s i t y o f L o n d o n - 8 2 - I m p e r i a l o C n o d l o n l e g e L
158

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
3 . 1 T h e i n f l u e n c e o f p s y c h o l o g i c a l i n t e r v e n t i o n u p o -r n e l s t a r t e s d s c h a n g e s i n
3 . 1 . 1
un i v e r si t y s t u d e n t s f a c i n g a c a d e m -e i c x s. a m
V a l i d a t i o n o f a c a d e m i c e x a m i n a t i o n a s a s t r e s s u n i n v d e u r c s i e r t y f s o t r u d e n t s
Th is s t u d y was d es i gn ed t o e xamin e th e h yp oth es is th at an ticip atin g an acad emic
e x a m i n a t i o n i n d u c e s s t r e s s a n d -r s t e r l e s a s t e d c h a n s g in e u n ivers it y s tu d en ts . Th e le vels o f s tres s
p e r c e p t i ( o P n e r c e i v e d S t r e s s S c o r e a n d S t a t e a n x i e t y s c o r a e n ) d N K -cel l p e r c e n t a g e s a n d N K
c y t o t o x i c a c t w i e r v e i t e x y a m i n e d i n u n i v e r s i t y s t u f d a e c n t i s n g a c a d e m i c e x a m (E i n xams a t i ) o n
an d comp ared wi th res u lt s o b t a i n e d i n t -e h x e a m n o n p e r i o d s o f u n i v e r s i t ( y N o -e l n i x a f m e ) in o r d e r t -s o tres s d as e s oci t at e ed c ch t a n ges . e In x ad a d ition m , C D 4 a n d C -cell D 8 p ercen T tages were e xami n ed .
3 .1 .1. 1 Im p a c t o f i a n a c t i a o n d u e p o m n i p s c y c h o l e o g x i c a l m m e a s u r e s o f n s x t i r e s t s y a n d a
P ercei ved s tres s l e v e l s ( P S S )
Th ere was a s i g n i f i c a n t i n c r e a s (t e = 2 , . d1 f = 2 1 , p = 0 . 0 4 5 ) in th e level s o f th e P SS at th e
E x a m s c o m p a r e d t o t h -e e x a N m o n t i m e p o i n t [T a b l e 7 a n d F i g u 6]. r e 1
T able 7: M e a n ( 9 5 % C . I . ) P S S s c o r e -e s xa a m t a n t d h E e x a N m o t n i m e p o i n ts
P S S
Non-e x a m Ex ams
Me a n s c o r e 21.5
26.2
( 9 5 % C . I . ) (18.6 - 24.5) (22.8 – 29.6)
n 22 22
Mean (95% C.I.) Perceived Stress Scores
Mean (95% C.I.) of PSS score
40
30
20
10
0
N =
2 2
Non-exams
p = 0 . 0 4 5
P h . D . a t U n i v e r s i t y o f L o n d o n - 8 3 - I m p e r i a l o C n o d l o n l e g e L
2 2
Exams
F i g u r e 6: 1 M e a n ( 9 5 % C s . c o I r . e s at ) the P S Non-e S x a and m E x a m t i m e p o i n ts

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
C o n c l u s i o n :
Pe r c e i v ed s t r e s s level s we re in creas ed i n u n i v e r s i t y s t u d e n w t h s e n f a c e d academi w i t h c
e x a m i n a t i s. o n
S t a t e n x a i e t y l e v e l s
T h e s t u d e n ts w e r e s h o w n t o mo b e re a n x i o u s (t = 2 .1 , d f = 2 4 , p = 0 . 0 4 8) at th e Ex am
t i m e p o i n t t h a n at th e N o n -e x a t i m e p o i n t [Tab le 8 a n d F i g u 7]. r e 1
T able 8: M e a n ( 9 5 % C . I . ) S t a t e a n x i e t y s c o r e s i n -e xa t m h e and S T E A xa I m a t i t me t p o h i e n ts N o n
S t a t e a n x i e t y i n t h e S T A I
Non-e x a m Ex ams
Me a n s c o r e 36.6
41.8
( 9 5 % C . I . ) (32.7 - 40.5) (38.5 – 45.1)
n 25 25
Mean (95% C.I.) of State score in STAI
50
40
30
20
10
0
N =
2 5
Non-exams
P h . D . a t U n i v e r s i t y o f L o n d o n - 8 4 - I m p e r i a l o C n o d l o n l e g e L
2 5
Exams
Fi gur e 17: M e a ( n 9 5 % C . I . S ) t a t e a n x i e sc t o y r es in t h e ST AI a t t h Non-exam e and E xa m t im e p o i n ts
C o n c l u s i o n :
Mean (95% C.I.) State Scores in the STAI
p = 0 . 0 4 8
Ac a d e m i c e x a m i n s a t i n i c o r e n a sed a n x i e t l y e v e l in s u n ivers it y s tu d en ts .
3 .1 .1.2 Im p a c t o f inations a c a d u p e o n m i m m c u n e e p a r x a m a e t m e r s
Previou s r e s earch s u g g e s t e d t h a t t h e l e v e l s o f N K c ( N y t K o C t A o ) x an i d c N a K c -cel t i ls v i t y
ma y b e a s s o c i a t d e w i t h p s y c h o l o g i c a l s t r e s s , i . e . t h e es h y a p r o e t h t e s h a -in t d u ced e s tx res a s m
d e c r e a s e s t h e N K c y t o t o -c x e l i l s c i n a t h c e t u n i v e r i s i n t ts y . y Hen s t u ce a d e n d t h e l
th is s tud y was d es i gn ed t o ex amin e th es e h yp oth es es with an ad d ition al exp lorat or y
in ves ti gat ion o f th e ef fect s u p on th e level s of C D4 an d C D 8 -cells T .

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
N K C A l e v e l s
T h e N K c yt ot oxi c act ivi t y le vels were n o t s t a t i s t i c a l l y ds if i feren g n i f t (t i c = a 0 n . t 2, l dy f =
2 0 , n s) b et ween th e N o n -e xam an d E x a m t i m e p o i n ts [Ap p e n d i x 6 : T a b l -7]. e A
C o n c l u s i o n :
A n t i c i p a t i o n o f a c a d e m i c e x a m i s n da id t i no ot n a f f e c t th e l evel s of N KC A.
N K -c e l l -c a e l l n l d e v e l T s
Th e res u lt s f r o m 2 s tu 6 d en ts sh ow th at n on e of th e -cell N K ( t = 0 . 3 , , d f n s), = 2 C 5 D -4
T
cell (t =0.6, d f = 2 5 , n s) o r C -c D e 8 l l (t T =0.2, d f = 2 5 , n s) p e r c e n t a g e s w e r e s ign if ican tl y
di f f e r t be etween n th e N o n -e xam an d E x a m t i m e p o i n ts [Ap p e n d i x 6 : Tab le A-8].
C o n c l u s i o n :
p ercen t age.
S u m m a r y :
An t i c i p a t i o n o f a c a d e m i c e x a m i s n da id t i no ot n a f f e c t N K -c e l l a n d C D 4 a n -c d e l l C D 8 T
T h e d a t a i n d i d c a th t at e an an ti ci p at ion of acad emic e xamin ation s in d u ces s tres s an d
p r o v o k e s a n x i e t u ny ivers i n it y s tu d en ts . Howev er, th e acad emic e xa min ation s d id n ot ap p ear to
affect t h e l e K-c v e l l s , o f C D 4 N -cells a n d o r NC K D 8 c yt ot T o xi c act i vi t y in th e u n ivers it y
s t u d e n t s, i n t h i s s tu d y.
It is con cl u d ed t h at acad emi c ex ams a re a valid s tres s fu l li fe e ven t (s tr es s or) to in cr eas e
s t r e s s a n d a n x i e t y l e v e l s f o r u n i v e r s i t y s t u d e n t s ; b u t th at acad emic exams d id n ot a p p ear to
p r o v i d e c o n c u r r e n t c h s a in n g e i m m u nol o gi cal p ara met ers , i.e. le v e l s -c e o l f l -cells s , N K an T d
NK c yt ot o xi c act i vi t y.
3 .1 .2 D i f f e r e n c s e in the le vel s of ly m ph ocy te s u b s e t s a n d NK c y t o t o x i c a c t i v i t y ( N K C A )
b e t w e e n
u n i v e r s i t i y t h s t h i u d g e percei h n t a ve s n d d s tres w l s l o e v w e l s
Th e p revi ou s s ect i on s u g ges ted th at an an ticip ation of ac ad emic e xamin ati on s d id not
a f f e c t t h e l e v e l s i mmu o f t nh e e p aramet er s . H o w e v e r , a d s e s c r i b e d i n t h e i n t r o d u c t i o 1 n .2 .3 [ .2
P h . D . a t U n i v e r s i t y o f L o n d o n - 8 5 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
a n d 1 . 2 . ], 4 i . n d 3 i v i d u a l ’s p ercep ti on of s t r e s s h as b een s h own to b e m o r e a s s o c i a d t with e
i m m u n e p a r a m e t e r s, p a r t i -cell c u p rofi l la es r , th l an y a s t r e N s s K f u l l i f e e v e n t i t s . e Hen l f ce, in this
s e c t i , o i n m m u n e p a r a m e t e r s ( -c N K e l l s [ 3 -l . y m 1 . p h 2 o c . y t 1 e s ] [ , 3 . 1 . T 2 . 2 ] ) w e r e c o m p a red in two s u b grou p s of s tu d en ts a s s e s s e t d o b s tres e s ed an d n o t -s tres s ed indi v i d u a l accord s in g to th ei r
P S S s c o r e s. T h e u n i v e r s i t y s t u d e n ts , wh o filled th e P SS qu es tion n ai res an d h a d b lood collecti on
fou r wee ks a ft er recru i t men t , w e r e d i v i d e d i n t o two s u bg r o u p s o n t h e b a s i s o f the PSS (Med ian
= 2 2 .5 , Mean = 2 3 .1 , St a n d a r d d e v i a t i o n = 7 . an 7 ) d lab el led as N o t -s t r e s s and e d S t r e s s e d
i n d i v i d u a l in s t h i s s tu d y:
S t r e s s e i d n d i v i d u a l s : P S S s c o r e w a s m o r e t h a n o r e q u a l t o 2 2
N o t -s t r e s s i e n d i v i d u a l s : P S S s c e o r w a s l e s s t h a n 2 2
Th ere was n o s t at i s t i cal l y s i gn ifican t d iff eren ce in th e n u mb ers of S u b j e c t s b etwee n th e
N o t -s t r e s s e d a n d S t s r u e b s g s r o e u d p s w i t h r e g a r d t o g e n d e r d i s t r i b u t i Ap o n p [ e n d i x 6 : T a b l -9]. e A
3 .1 .2 .1 D i f f e r e n c e s in th e p e r c e n t a g e o f N -cells K an d th e level o f N K c yt oto xic acti vit y
( N K C A ) b e t w e e n u n i v i e t r h s i h t i y g p ercei h s ved t a u n s tres d e s l n l e v t e o l s w w
Re s e a r c h a s s u g g e s t ed t h -c a e t l l s N a K r e a f f e c t e d b y s t r [1 e .2 s .3 s .2 p an e r d c e p t i o n
1 . 2 . 4 ]. . 3 A c c o r d i n g l y , t h i in e s if, in s u nt ivers u id t y sy tu d en w ts a , s p e r f o r m e
p erceived s t res s l ev el i s as s ociated with
1 . o w L N -c K e l l p e r c e n t a g e
2 . Low N K c yt o t o x i c a c t i v i t y l e v e l, a n d
3 . L o w p e r-N K -c e l l c y t o t o x i c . a c t i v i t y
In ad d it ion , t h e i n f l u e n c e o f g e n d e r u p o n t h e s e p a r a m e t e . r s w a s i n v e s t i g a t e d
NK-c e l l l e v e l s
There was n o s i gn ifi can t d i f f e r e n c be etw een th e S t r e s s a e n d d N o n -s t r e s s e u d b gr o u p s in th e p ercen tages of N K -c e l l s (t = 0 . 7 , d f = 3 9 , [Ap n s ) p e n d i x 6 : T a b le A-1 0 ].
G e n d e r d i d n o t a p p e a to r aff ect th e res u lt s . T h e r e w a s n o s i g n i f i c n a d n e t r v g s e . s t r -e
s s
p e r c e p t i o t n e r i a c n t i o n ( F = 1 . 7 , d f = ; m 3 a 9 l , e : n t s = 1 .1 , d f = 1 8 , n s ; an d female : t = 1 .5 , d f =
1 8 , n s ) [Ap p e n d i x 6 : T a b l es -1 A 1 a n d ]. 1 2 Hen ce, it was c on cl u d ed th at th ere was n o gen d er
b i a s w i t h r e g a r d t o t h e r e s u l t al f r ys o is m b et c ween o m p a tr h e i S s t o n r e s a s n an e d N o t -s t r e s s e d
s u b grou p s .
P h . D . a t U n i v e r s i t y o f L o n d o n - 8 6 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
With reg ard t o gen d er d i ffe ren ce, h o w e v e r , ma l e s t u d e n t s
h a d a t r e n d - t o w a r d s
c e l l p e r c e n t a g e th s an fe mal e s tu d en ts (t = 1.9, d f = 3 8 , p = 0 .0 6 6 ) [Tab le 9 a n d F i g u 8]. r e 1
C o n c l u s i o n :
T able 9: M e a C.I n .) N K ( -c e 9 l l 5 p e % r c e n t a g e s i n m a l e a n d f e m a l e s t u d e n t s
N K -c e l l (%)
Ma l e Fe m a l e
Me a n l e ve l 11.0
8.0
( 9 5 % C . I . ) (8.5 – 13.5) (6.1 – 10.0)
n 20 20
Mean (95% C.I.) NK-cell (%)
1 5
1 0
5
0
m a l e f e m a l e
Fi gur e 18: M e a n (95% C.I .) NK-c e l l p e r c e n t a g e s i n m a l e a n d f e m a l e s t u d e n t s
Th e r e w a s i n o f d f e r e -c n e c l l l e v e l s i b e n t w e e n N s K t r e s s e d a n d n o t-s tres s ed s tu d en ts .
M a l e s t u d e n t s a p p -c e l a l r p e e r c e d n t a g t e t s h o a n f h e m a l v , e bs e u t th ih s d i ifferen g h ce e r N K
was n ot s t at i s t i cal l y s i gn i fi can t.
Na tura l K i l l er cy toto xi c a cti vity (NK C A) l e v e l s
p = 0 . 0 6 6
The S t r es s e d s t ud en ts h ad s i gn ifican tl y lo wer N KC A le vel s c omp ared t o th e N o n -s t r e s s e d
s tu d en ts (t = 2.4, d f 9 = , p 3 = 0 . 0 ) 2 [T 3 a b l e 1 0 a n d F i g u 9]. r e 1
T able 10: Me a n ( 95% C.I .) l e v e l s o f N K C A ( % k i l l i n i g n ) the Not-s t r e s s and e d S t r e s s e s d u bgroups
N K C A (% ki l l in g )
Not-s t r e s s e d St re s se d
Me a n l e ve l 12.0
5.8
( 9 5 % C . I . ) (7.7 – 16.3) (2.8 – 8.7)
n 20 21
P h . D . a t U n i v e r s i t y o f L o n d o n - 8 7 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
NKCA levels (95% C.I.) at Time point 1
20
15
10
5
0
N =
2 0
Non- s t r e s s e d
P h . D . a t U n i v e r s i t y o f L o n d o n - 8 8 - I m p e r i a l o C n o d l o n l e g e L
2 1
St r e s s e d
Fi gur e 19: M ea n (95% C.I .) N K C A (% k i l l i n g i ) n t he N ot -s t r e s s e a d n d S t r e s s subg e d r o u ps
Ge n d e r d i d n o t a p p e a r t o a f f e c t th e res u lt s . T h e r e w a s n o s i g n i f i c a n t g e n d e r v s . - s t r e s s
p ercep ti on in teract ion ( F = 0 .6 , d f = 3 9 , n s ). Th is was c on fi rmed wh en th e S t r e s s an e d N o t -
s t r e s s e s u d b g r o u p s w e r e c o m p a r e d i n e a c h g e n d e r . The s e p S a t r a e t s e s l male e y d s t u d en ts h ad
s i g n i f i c a n t l y r l No KC w e A level s c o mp ar ed to th e N o n -s t r e s s male e d s t u d e n t s (t = 2 .2 , d f = 1 9 , p
= 0 . 0 3 8 ) [Tab le 1 1 a n d F i g u r e ]. Th 2 0 e s ame tren d was s h own in fe male s tu d en ts , b u t it d id n ot
a c h i e v e s t a t i s t i c a l s i g n i f i c a n c t e = ( 1 . 1 , d f = 1 8 , [Ap n s ) p e n d i x 6 : T a b l -13] e . Wi A t h regard t o
d ifferen ce b et ween mal e an d female s tu d en ts , t h e r e w a s n o s i g n i f i c a n t d i n f th f e r le evel n c e s of
t h e N K C A (t = 0 .1, d f = 3 9 , n s) b e t w e e n m a l e a n d f e m a l e s t u d e n Ap t s p [ e n d i x 6 : T a b l -14]. e A
T a b l e 11: M e a n ( 9 5 % C . I . ) l e v e l s o f N K ) C in A the ( Not-st % k i r es l se l d i and n g S t r e s s m e a d l e s t u d e n t s
N K C A (% k i l l ) i n g
Not-s t r e s s e d St re s se d
Me a n l e ve l 12.9
4.7
( 9 5 % C . I . ) (6.6 – 19.2) (1.2 – 8.2)
n 11 10
NK cytotoxic activity (%killing)
NK cytotoxic activity (%killing)
Mean (95% C.I.) NKCA in male (%killing)
2 0
1 5
1 0
Fi gur e 20: M e a n ( 9 5 % C . I . )
5
0
p = 0 . 0 2 3
p = 0 . 0 3 8
N o t - s t r e s s e d S t r e s s e d
N K C le A ve ls ( % ki llin g) in t he N ot -s t r e s s e a d n d S t r e s s m e a d l e s t u d e n t s
Hen ce, i t was c on cl u d ed t h at th ere was n o gen d er b ias with re gard t o th e res u lt f ro m
comp ari s on an al ys is b et ween th e S t r e s s an e d N o t -s t r e s s su e d b grou p s .

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
C o n c l u s i o n :
St r e s s e d s t u d en t s h a d l o w e r l e v e l s o f N K C A c o m p a r e d t o t h e n o -s t t r e s s e d s t n u t d s. e
NKC A l evel s we re n ot s i gn i fican tl y d iff e ren t b etween male an d fe male s tu d en ts .
P e r -N K -c e l l c y t o t o x i c a c t i v i t y l e v e l s
It is kn own t h at N K c yt ot o xic a ctivit y (N KC A) is related t o th e n u mb er o f N K -c e l l s an d
th e p r o m i s c u i -cells. t y T o h i f s p t r o h m i t e i y s i s c u d N e K p e n d e n t u p o n f a c t o r s l i k e :-
1. R el at ive c o n c e n t r a t s i o o n f -cells, N K tar g et cel ls a n d ot h er is olated p e r i p h e r al m o n -o
n u c l e a r c e l l /or s ; a n d
2 . Pe r -c e l l c y t o t o x c i c t a i v i t y o -cells f . i n d i v i d u a l N K
Th e firs t h yp ot h es is was e xamin ed u s in g a c o r r e l a an t al i o ys n is b e t w e e -c e n l l N K
p e r c e n t a g e a n d C A N l K e v e l , a n d s h o w e d t h a t t h se tr r on e g w an a s d sa tat is ti cal l y s i gn ifican t
p os itive a s s o c i a t (r i o = n 0 .5 2 , p = 0 . 0 0 1 , n = 4 . 4 ) H e n c e , i t w a s c o n c l u d e d t h a t t h e n u m a n b d e r
c o n c e n t r a t i o n f -cells N K wer e on e of th e m o s t i m p o r t a n t f a c t f o r s t h e N K C A l e . v e l s
Ha vin g d em on s t rat ed t h i s p os itive c orrela tion , th e s econ d h yp oth es i s th at low le vel s of
p e r -N K -c e l l c y t o t o x i c a c t i v i t y a s s o c i a t e w i t h h i g h s t r e s s p e r c e p t i o n w a s e x a m i n e d . - T h i s p e r
N K -c e l l c y t o t o x i c , a c w ich t h i was v i t cal y cu lat ed as a f i g u r e o f a r a -cell t i o o f t h e
p e r c e n t a g e a s w a s s u g g e s t e d i n -a t n h a e l y m s i e t s o a f S e g e r s t r o m a n d M i l l e r [ 2 0 0 , 4 were ]
comp ared b et ween th e S t r e s s an e d N o t -s t r e s s se tud d en ts . Th e r e s u l t s s h o w t h a t the St r e s s e d
s t u d e n t s a h t a r d e n d t o w a r d l s o w e r le vel s o f p e r-N K -c e l l c yt oto xic acti vit y (calcu la ted as a ratio
o f N K C A -cell t o p e r c e N n K t a g e) co mp ar ed to th e No n -s t r e s s e tu d e n ts (t = 2.0 , d f = 3 9 , p =
0 . 05 6 ) [Tab le 12 a n d F i g u r 2 e 1].
T able 12: M e a n ( 9 5 % C . I . ) r a t i o s NK-c o f eN ll K in C A t he t Not-st o re s se d and S t r e s s e t d u d e n t s
N K C A to NK-c e l l r a t i o
Not-s t r e s s e d St re s se d
Me a n r a t i o 1.29
0.64
( 9 5 % C . I . ) (0.74 – 1.84) (0.25 – 1.02)
n 20 21
P h . D . a t U n i v e r s i t y o f L o n d o n - 8 9 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Per-NK-cell cytotoxic activity
Mean (95% C.I.) ratios of NKCA to NKC %
2 . 5
2 . 0
1 . 5
1 . 0
0 . 5
0 . 0
N o t - s t r e s s e d S t r e s s e d
Fi gur e 21: M ea n (95% C.I .) p e r -N K -c e l l c yt ot ox ic ac t i vi t y ( c a l c u l a t e d as a r at i o : NK c yt oto xic a c t i v i t y
( N K C A ) / NK-c e l l p e r c e n t a g e ( C%)) N K in t he Not-st r es s ed a n d S t r e s s subgroups e d
Gen d er ap p eared n o t t o i n f l u e n c e t h e r e s s u l i t g s n i f i c . Th a n t ere l y was n o s i gn ifi can t
g e n d e r v s . s t r -p e s e s r c e p t i o n i n t e r a c t i o n ( F = 1 . 4 , d f = 3 9 , n s ) . T h s i w a s c o n f i r m e d th e w h e n
S t r e s s and e d N o t -s t r e s s e s u d b g r o u p s w e r e c o m p a r e d i n e a c h g e n d e r . Th s e p St a r a e t s e s l e y d
male s t u d e n t s l h o a w d e r p e r -N K -c e l l c y t o t o x i c a c l t e i v e v l i co s t mp y ared to th e No n -s t r e s s e d
m a l e s t u d e n ts (t = 2 .3 , d f = 1 9 , p = 0 . 0 3 5 ) [ T a b l e 1 3 a nd F i g u r e ]. Th 2 2 ere was , h o wever , n o
s tatis tical l y s ign ifi can t d ifferen ce b etwee n th e N o t -s tr es s ed a n d S tr es s ed f e m a l e s t u d e n t s t ( = 0 .5 ,
d f = 1 8 , n s ) Ap [ p e n d i x 6 : Tab le A-1 5 ] . With reg ard to d ifferen ce b etween male a n d female
s t u d e n ts , th e r e w e r o e s i g n i f i c a n t d i f f e r e n c e s b e t w e e n m a l e a n d f e m a l e s t in u d th e n e t rat s ios o f
t h e N K t C A o -c e l l N p K e r c e n t a g e (t = 0 . 1 , d , f n = s) [Ap 4 0 p e n d i x 6 : Tab le A-1 6 ] .
T able 13: M e a n ( 9 5 % C . I . ) r -c a et ll in i t ho e s Not-st o re f s se d and N K C S A t r e t s s o m e a d l e N s K t u d e n t s
N K C A to NK-c e l l r a t i o
Not-s t r e s s e d St re s se d
Me a n r at io 1.38
0.33
( 9 5 % C . I . ) (0.53 – 2.24) (0.14 – 0.52)
n 11 10
Per-NK-cell cytotoxic activity
Mean (95% C.I.) ratios of NKCA to NKC % in male students
2 . 5
2 . 0
1 . 5
1 . 0
0 . 5
0 . 0
p = 0 . 0 5 6
p = 0 . 0 3 5
N o t - s t r e s s e d S t r e s s e d
Fi gur e 22: M ea n (95% C.I .) p e r -N K -c e l l c yt ot ox ic ac t ivit y ( c a lc ula te d as a r at io : N K C A / NK-c e ll
p e r c e n t a g e) in t he N ot -s t r e s s e d a S n t r e s s m e a d l e s t u d e n t s
P h . D . a t U n i v e r s i t y o f L o n d o n - 9 0 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Hen ce, i t was c on cl u d ed t h at th ere was n o gen d er b ias with re gard t o th e res u lt f ro m
comp ari s on an al ys is b et ween th e S t r e s s an e d N o t -s t r e s s su e d b grou p s .
C o n c l u s i o n :
I t a p p e a r s t h a t r e s s e d s t u d e n t m s a y h a v e l o w e r l e v e l s o f p -N e r K -cel l c yt ot oxi c act ivi t y
c o m p a r e d t o t h e n o t-s t r e s s e d s t u d e n , t s a n d p o s s i b l y , b e c a u s e o f t h e s m is a l l s a m p l e s i z e ,
a c h i e v e d s t a t i s t i c a l s i g n i f ican ce on l y f or male s tu d en ts .
3 . 1 . 2 . Differen 2 ces in th e p e r c e n t a g es o f T-cells b etween u n ivers it y s tu d en ts with h i g h a n d l o w
p erceived s t res s l e v e l s
As s ociat i on s b et ween s tres s p e r c e p t i o n a T-cells n d h a v e b een in con s is ten tl y rep ort ed
[1 . 2 . 3 . 2 a n d 1 ]. . Hen 2 . 4 ce, . 3 th is s tu d y w as p erfor med to d etermin e i f th ere a re an y as s ociati on s
b etween p ercei ved s tres s level a n d C D -c 4 e T l l a n d / -c o e r l l p erc C D en 8 tages T in u n ivers it y
s tu d en ts . In ad d i t i on , t h e i n flu en ce of gen d er u p on th es e p arameters was in ves ti gat ed .
Ther e w a s s i n g o n i f i c a n t d i f f e r e n bc etw e een th e S t r e s s a e n d d N o n -s t r e s s i e n d i v i d u a l in s
t h e C D 4 o r C D 8 T-c e l l l e v e l (C s D 4 -cel T ls : t = 1 .4, d f 9, = n 3 s; C D -cells 8 T : t = 0 .8 , d f = 3 9 ,
n s ) [Ap p e n d i x 6 : T a b l -1 e 7 ]. T h A e r e w a s n o s i g n i f i c a n t g e n d e r v s . -p er s t cep r e s ts io n in teract ion ( C D 4 -c T e l l s : F = 0 . 8 , d f -c e l = l s : 3 F 9 , = 0 . n 5 s , ; d f = a n 3 d 9 , n C s D ) . 8 con T h T firm i s w ed a s
w h e n th e S t r e s s an e d N o t -s t r e s s e s u d b g r o u p s were co mp ared in each g en d er s ep aratel y. Th ere
wa s n o s ign ifi can t d i f f e r e n c be etween th e N o t -s t r e s s and e d S t r e s s e s t d u d e n t s ( m a l e : C D 4 - T
c e l l s : t = 1 . 1 , d f = 1 ; 8 C , D n 8 s -c T e l l s : t = 1 .1 , d f = 1 8 , n s [Ap p e n d i x 6 : T a b l -1 e 8 ]; an A d
f e m a l e : C D 4 -c e T l l : t = 1 . 7 , d f = 1 ; 8 CD , n 8 s -c T e l l : t = 1 .1 , d f = 1 8 , n s [Ap p e n d i x 6 : T a b l - e A
1 9 ]). Hen ce, i t was con cl u d ed th at th ere was n o gen d er b ias with re gard t o th e res u lt fro m
comp ari s on an al ys is b et ween th e S t r e s s ed an d N o t -s t r e s s su e d b grou p s .
G e n d e r a p p e a r e d t o i n f l u e -cells n c e ( F t = h 6 .0 e , d f r = e 1 s , p u = l 0 t .0 1s 9), bo uf t C D 4 T
n o t C D -c 8 e l T l s ( F = 0 . 0 3 , d f = 1 , n s ) . -cell F e m p er a cen l e tages s t th an u d e n t s h a v e
male s tu d en ts (t = 2.4, d f = 3 8 , p = 0 .0 2 0 ) [Tab le 1 4 an d F i g u r e 23]. Th e r a e s n o s w i g n i f i c a n t
d ifferen ce b et ween m a l e a n d f e m a l e s t u d e n t s C i D n 8 t -c h e T l l p e r c e n t a g e (t s = 0.4, d f = 3 8 , n s )
[Ap p e n d i x 6 : T a b l -2 e 0 ] .
A
P h . D . a t U n i v e r s i t y o f L o n d o n - 9 1 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
C o n c l u s i o n :
T able 14: Me a n ( 95% C.I .) C D 4 -c T e l l l e v e l s ( % ) o f m a l e a n d f e m a l e
CD4 T-c e ll (%)
Ma l e Fe m a l e
Me a n l e ve l 43.2
48.7
( 9 5 % C . I . ) (39.9 – 46.4) (45.5 – 52.0)
n 20 20
Mean (95% C.I.) CD4 T-cell (%)
5 0
4 0
3 0
2 0
1 0
0
m a l e f e m a l e
F i g u r e 23: M e a n (95% C.I .) C D 4 -c e T l l l e v e ( l % s ) o f m a l e a n d f e m a l e s t u d e n t s
Th e r e w a s s i n g o n i f i c a n t d i f f e r e n c e i n o r C D C D 4 8 T-c e l l l e v e l s b en e t sw tres e s ed an d
n o t -s t res s ed s tu d en ts . F e m a l e s t u d e n t s s h o w -c e ell d p ercen h i tg ages h e r th an C mal D 4 e T
s tu d en ts i n t h i s s tu d y.
S u m m a r y :
CD4 T-cell percentages
p = 0 . 0 2 0
T h e a n a l y s e of N KC A a n d p e r-N K -cel l c ytot oxic activit y l e v e l s s u g g e s te d that the
s tu d en ts wi th h igh s tres s p ercep tion ( t h e s t r e s s e d i n d i v i d u a ls ) m a y h a v e l o w e r l e v e l s o f
a n d p e r-N K -c e l l c y t o t o x i c ca omp c t ai red v i t to y th e s tu d en ts wh o exp res s ed a l o w l e v e l o f s t r e s s
( t h e n o t-s t r e s s e d i n d i v i d u a l s . ) Th ere were n o s ign ifi can t d iffe ren ces b etween th e s tres s ed an d
n o t -s t r es s e d s t u -c d e l n l t s o r i C n D 4 -c N a e K l n l d p C e D r 8 c e n t T a g e th s es , e res a n ud lt s h ad n o
g e n d e r b i a s l ; t a h o u g m h a l e s t u d e n t -c s e l l h a a d n d h l i o -c g w e h l e l e r r p cen e C D tages N 4 K tT h an
f e m a l e s. He n c e , i t i s s u g g e s t e d t h a t g e n d e r m a y n o t n e e d t b o e s e p a r a t e l y a n a lys ed wh en th e
l e v e l s o f t h e N K C -c A e l o l r s a p n e d r c C D e 4 n -cells t a n a ad re g ce oC mp D s 8 ared o T if n N K
r e l a t i o n s h i p w i t h t h e l e v e l s o . f s t r e s s p e r c e p t i o n
T h i s s t u d y h a s s h o w t n t h e a r e a r e a s s o c i a t i o n s b e t ’s w pe ercei e n o vn ed e s tres s lev el an d
o n e ’s l e v el s f o N K C A ; a n d se t h f e i n d i n g s u p p o r t p r e v i o u s r e p o [ r I t n s t r o d u c t i o n : 1 . 2 . 4 . that 3 ]
P h . D . a t U n i v e r s i t y o f L o n d o n - 9 2 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
th ere are i n t e r a c t i o n s a m o n g t h e p r o p o s e d i n -n t e u g r o-e a t n e d d o c r p s i y n -i c o h m o m u n e n e t w , o r k
an d that it is warran t ed t o i n ves tig ate th is n etwork fu rth er [3 .3 an d 3 .4 ].
3 . 1 . 3 T he in fl uen ce of ps y ch ol og ica l interven tion u p o n s t r e s s-rela te d cha ng es in
u n i v e r s i t y s t u d e n t f s a c i n g a c a d e m i c e x a m i n a t i o n s
Th e ob j ect i ve of this s eri es o f in ves tigati on s was to d eter min e if th e p racti ce o f
p s yc h o l o g i c a l c o p i n g s k i l l s w o u l d r e d u c e :
1 . I nc r e a s e d l e v e l erc s eived o f s p t r e s s ( P S S ) an d an xiet y ( S t a t e s c o r e o f t h e S T A , I )
2 . S t r e s s-r e l a t e d l o w N K C A l e , v e l a s n d
3 . St r e s s-rel at ed d ecreas e in N K -c e l l p e r c e n t a s g e
in u n ivers i t y s t u d en t s faci n g acad e mic e x amin ation s . Th e le vel s w e r e c o m p a r e d b e t w e e n th e
recru it men t b a s e l i n e t i m e p o i n t an d th e E x a m t i m e p o i n t. Psych ol ogical in terven tio n was given
p rior t o t h e ex ami n at i on s . In a d d i t i o n , t h e e f f e c ts of p s ych olo gical in ter ven tion u p on C D4 , C D8
T-c e l l p e r c e n t a g e s w e r e e eth x od p . l o r e d b y u s i n g
3.1 . 3 . 1
Ef f e c t o f p s y c h o l o g i c a l i n t u p e on r v se tn res t i s po ercep n ti on in u n ivers it y s tu d en ts
a n t i c i p a t i n g a c a d e m i c e x a m i n a t i o n s
P e r c e i v e d S t r e s s l e v e l s ( P S S )
Th e P S S q u es t i on n ai re was n ot read y fo r u s e wh en th e s tud en t s were recru ited for t h e
b a s e l e i n a s s e s s m e n t s. H o w e v e r , 3 2 p a r t i c i p a n t s c o m p l e t ne aire d t at h te h e q Exa u e s m t i ime o n
p o i n t . A N O V A s h owed th at th ere w as n o s tatis tical d ifferen ce b etween t h e t h r e e s g (F r o u = p 0 . , 5
d f = 2 9 , n s ), a n d e x p l o r a t o r y p o s t-h o c t-tests s h owed n o s i g n i f i c a n t d n i c f e s f e (R r e el axat ion c o n t r o l vs . S e l f-h yp n o s i s : t = 0 .6 , d f = 1 9 , n s; R elaxation con t r ol vs . J oh rei : t = 0 .3 , d f = 1 8 , n s )
[Ap p e n d i x 6 : T a b l -2 e 1 ]. F A u r t h e r , t h e r e w a s n o s i g n i f i c a n t d i in f f e th r e n Pc Se S s level s
b e t w e e n th e t h r e e g r o u p s w i t h r e g a r d t o ;-
Distri b u ti on of n u mb ers of the p articip an ts in th e N o t -s t r e s s e a d n d S t r e s s e d
s u b grou p s ( N o d i f f e r e n c e s : P e a r s o are n ' : s R e l C a h x i a t i s o q n u n t r c o l s v s . S e -l
f
h y p n o s i s = 0 .2 ; R e l a x a t i o n o n c t r o l s v s . J o h r e i = 2 . [ 6 T ) a b l e ] 1 ; 5 a n d
Gen d er bias [Ap p e n d i x 6 : T a b l es -2 A 2 a n d A-2 3 ].
P h . D . a t U n i v e r s i t y o f L o n d o n - 9 3 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
T able 15: T h e n u m b e r s o f p a r t i c i p a n t i u n p s t ( S h e l f-h t y h p r n o e s e i s g , r o J o h r e i a n d R e l a x ontrol) a t i o n in c
t he N ot -s t r e s s e d a n d S t sr ubgr e s s oe up d s ba s ed on the P SS s c or es at th e E xa m t i m e po i n t
C o n c l u s i o n :
Group
Not-s t r e s s e d
S t r e s s e d
P h . D . a t U n i v e r s i t y o f L o n d o n - 9 4 - I m p e r i a l o C n o d l o n l e g e L
T ot a l
S e l f-hy p nos i s 5 7 12
J o h r e i 7 4 11
C o n t r o l s
3 6 9
T ot a l 15 17 32
St u d e n t s p r a c t i s i n g p s y c h o l o g i c a s l p rior i n to t e acad r v e emi n t c i exa o n ms d id n ot s h ow an y
s ign ifican t d i f f e r e n c e s i n p e r c e si tres v e s d level s at th e E x a m t i m e p o i n t wh en co m p ared with
s t u d e n t s i n t h e R e l a x a t i o n . c o n t r o l g r o u p
Sta te a n x i e t y l e v e l s
Th i r t y f i p v a e r t i c i p a n t s c o m p l e t e d t h e S t a t e s c o r e o f t h e S T A I q s elin u e s e t i o n n a i r e s a t b a
an d th e E x a m t i m e p o i n t, al l owin g fo r an an al ys is of an xiet y l evels in th e th ree gr o u p s b efore
t h e p ch s y ol ogi cal in terven ti on p eri od an d later at th e exa m s tres s p eri od .
An x i e t y l e v e l s i n c r e a s e d s i g n i f i c a n t l y a t t h e E x a m s s t r e s s t i m e p o i n t c o m p a r e d t o b a s e l i n e
in all th ree gr ou p s ( F = 1 1 .0 , d f = 3 2 , p = 0 .0 02 ). Alth ou gh rep eated meas u re ANO VA s h owed
that there was n o s i gn i fi can t d iff eren ce in th e State an xiet y s co res in th e ST AI b etween th e th ree
g r o u p s a t b a s e l i n e a n d E x a m t i m e p o i n t, i .e. th ere w as n o time x g r o u p i n t e r a c t (F i = o n 0 .0 2 , d f
= 3 2 , n s ), p os t h oc t-t e s t s s h o w e d t h a t th e i n c r e a s e s w e r e s t ticall a t i s y s ign ifi can t fo r th e
R e l a x a t i o n o n c t r o l (mean ch an ge = 6 .8 , t = 3 .3 , d f = 9 , p = 0 .0 2 7 ) a n d S e l f-h yp n os i s (mean
ch an ge = 4 .9 , t = 3 .3 , d f = 1 2 , p = 0 . 0 ) 0 g 6 r o u p s b u t n o t f o r t h e J o h r e i (mea g r o u n p ch s an ge =
4 .2 , t = 1 . 1 , d f , n = s) 1 [ Tab 1 le 1 6 a n d Fig u r e 24]. An al ys es of th e d ata b y gen d er s h owed th e
s a e m t r e n d s [ A p p -2 e 4 n a n d i ]. 2 x 5 6 : T a b l e s A
T able 16: Me a n ( 95% C.I .) S t a t e a n x i e t y s the c o r S e s l f-hypnosis, i n Johrei and Re la xa t io n c on tr ol groups at b a s e l i n and e t he Ex a m t i m e po i n t
S t a t e s c o r t h e e i S T n A I
B a s e l i n e
E x a m s
S e l f-h y p n o s i s J o h r e i C o n t r o l s S e l f-h y p n o s i s J o h r e i C o n t r o l s
Me a n s c o r e 37.3 34.8 31.5 42.2 39.0
38.3
( 9 5 % C . I . ) (34.0 - 40.6) (29.7 – 40.0) (28.5 - 34.5) (39.1 - 45.4) (33.9 – 44.1) (31.9 - 44.7)
N 13 12 10 13 12 10

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Mean (95% C.I.) State scores in the STAI
4 0
3 0
2 0
1 0
0
S e l f - h y p n o s i s J o h r e i C o n t r o l s
B a s e l i n e
E x a m s
Fi gur e 24: M e a n (95% C.I .) S t a t e a n x i e t y s c o r e s i n t h e S T of A I t he t hr e e gr oups a t ba se line and the Ex a m
t i m e p o i n t
C o n c l u s i o n :
A n x i e t y l e v e l s i n d c r e i a s n e u n i v e r s i t y s t u d e n t s f a c i n g a c a , d an e m d i th c e e x a m i n a t i o n
train in g an d p ract ice of J oh rei a p p e a r ed t o h e l p s t u d e n t s t o c o n t se r o pl ro vo t h ked e level s o f
a n x i e t alth y ou gh th is a n t i -an xi et y ef fect d i d n o t a c h i e v e a s t a t i s t i c a l . s i g n i f i c a n c e
3 .1 .3 .2 Effect s o f p s y c h o l o g i c a l i n t e r v e s n t r i e s o s-r n e l a u t p e d o n ly m p h o c y t e s u -p b o p u l a t i s o in n
u n i v e r s i t y s t u d e n ts a n t i c i p a t i n g a c a d e m i c e x a m i n a t i o n s
NK cy toto xi c a cti vi ty (NK CA ) l e v e l s
N K C A l e v e l s w e r e d e t e r m i n e d i n p e r i p h e r pa artici l b pl an o to s d at f th r e o Exa m m 3 1 ti me
p o i n t s . Du e to tech n ical d i f f i c u l t i , t e s h e N K C A l e v e cl ou s ld n ot b e col lect ed at th e b as elin e. T h e
mean level o f th e N KC A in th e R e l a x a t i o n c o n t r o l were g r no ot u p s i gn ifi can tl y d if feren t fr o m
t h o s e l e v e l s i n t h e S -h e l yp f n os is an d th e J oh rei g rou p s (R e l a x a t i o n c o n t r o l v s . S e l -h f yp n os is : t =
1 . 3 , d f , = n ; s 1 R 8 e l a x a t i o n c o n t r o l vs . J o h rei : t = 0 . 2 , 1 d 8, f n s) [Ap = p e n d i x 6 : T a b l e -2 A 6 ].
G e n d e r d i d n o t a p p e a r t -2 o 7 i a n -2 n f 8 ] d l . I u t A e w co n a s nc firmed e [ th at A p p e n d i x 6
th ere was n o g e n d e r b i a . s
C o n c l u s i o n :
p = 0 . 0 0 6
P s y c h o l o g i c a l i n t e r v e n t o t i o a n p p e d a i r d t o i n f l u e n c e N K C A l e v e l s o f u n i v e r s i t y s t u d e n t s
facin g acad emi c e xami n at i on s .
N o t s i g n i f i c a n t
N o t s i g n i f i c a n t
p = 0 . 0 2 7
P h . D . a t U n i v e r s i t y o f L o n d o n - 9 5 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
P eriph era l N K -c e l l a n d C D 4 a n -c d e l l C p D e r 8 c e n t T a g e s
P e r i p h -c e r l a l a n N d K C D 4 -c a e l n l p d e r c C e n D t 8 a g es we T re d et er min ed for 34
p articip an ts ( 1 9 m a l e a n d 1 5 f e ) m a [ l T e a b l ] e at 1 b7 as el in e an d th e E x a m t i m e p o i n ts a l l o w i n g
an al ys is of th e in fl u en ce o f p s yc h o l o g i c a l i n t e r v e n -s tres t i s as o s oci n at ed u ch p an o ges n . e x a m
T able 17: Number s of pa rt ic ipa nt s in t h e t hr ee gr o u p s a t t he E x a m t i m e p o i n t
N K -c e l l p e r c e n t a g e s
G r o u p
S e l f-h y p n o s i s J o hr e i
Re la xat io n
co n t r o l s
P h . D . a t U n i v e r s i t y o f L o n d o n - 9 6 - I m p e r i a l o C n o d l o n l e g e L
T o t a l
m a l e 7 7 5 19
f e m a l e 5 4 6 15
T o t a l 12 11 11 34
Ther e w a s n o d i f f e r e n c e b e t w e e n -c t ell h pe ercen t ta ges h r at e e g r o u p s
b a s e l i n e ( S e l f-h y p n o s i s a n d R e l a x a t i on o trol n c : t = 0.5, d f , = n 2 ; s 1 J oh rei an d R el axat ion c o n t r o l : t = 0.7, d f , = s). 2 n 0
R e p e a t e d m e a s u s r e AN OV A s h owed th at th ere is a s ign ifican t d if feren ce in th e ch an ges
fro m b as el i n e t o t h e Exa ms as s es s men t p oin t am on g th e t h ree gr ou p s ( F = 5 .8 , d f = 3 1 , p =
0 .0 07 ). A t t h e E x a m s p e r i o d , -c e l l t p e r h c e n t a r g e i n th e w Ra el s axation a d e c r e a s e
c o n t r o l g r (mean o u p ch an ge = 2 .1 , SD = 4 .7 , t = 1 . 5 , d f , = n s), b1 u0 t th is d id n ot ach ieve s t a t i s t i c a l s ig n i f i c a n c e . Ho w e v e r , th e c h a n g e -cell i p erc n en tages t h in e th e pN sK ych ologic al
in terven t i on gr ou p s were s i gn ific an tl y d i f f e r e n t , i . e . th ere w as a s ign i fican t time x g r o u p
i n t e r a c t ( i F o n = 5 . 8 , d f , p = = 3 1 0 . 7 0 ). Th i s w a s c o n f i r m e d b y f o l l o w i n g p o s t-h o c t-tes ts .
Th e r a e s n o s w i g n i f i c a n t c h a n g e i n -c e l l t p e h r c e n t a g m e e i n a t n h e S -h e N l yp f K n o s is grou p
(mean ch an ge = 1 .0 , t = 0 . 7 , S D , = d 4 f . 5 , = 1 n 1 s), b u t th ere wa s a s ign ifi can t in cre as e in th e
J oh rei gr ou p (me an ch an ge = 3 .2 , t = 6 .9 , SD = 1 .7 , d f =1 0 , p < 0 . 0 0 1 ) at th e E x a m t i m e p o i n t
[Tab le 1 8 an d Fi gu re 25]. A n a l y s e s o f t h e d a t a b y g e n d e r s h o w e d tren t h de s [ s Ap a m pe en d ix 6 :
T a b l -29 e s a n d A ]. 3 0
T able 18: Me a n ( 95% C.I .) l e v e l -c s e l l o f ( % the ) N S K i e l n f-hypnosis, Johrei and Re la xa t io n c ont ro l
( Contr ols) groups at b a s e l i n and e the E xa m t im e p o i n t
N K -c e l l s ( % )
B a s e l i n e
E x a m s
S e l f-h y p n o s i s J o h r e i C o n t r o l s S e l f-h y p n o s i s J o h r e i C o n t r l o s
Me a n l e ve l 9.6
7.6
8.8
8.6
10.8
6.7
( 9 5 % C . I . ) (7.7 - 11.5) (4.9 – 10.3) (6.3 - 11.3) (5.7 - 11.5) (8.1 – 13.6) (4.7 - 8.7)
n 12 11 11 12 11 11

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
NK cell percentages (95% C.I.)
2 0
1 5
1 0
5
0
N =
1 2
H y p n o s i s
1 2 1 1 1 1 1 1
J o h r e i
P h . D . a t U n i v e r s i t y o f L o n d o n - 9 7 - I m p e r i a l o C n o d l o n l e g e L
1 1
C o n t r o l ( r e l a x a t i o n )
B a s e l i n e
E x a m s
Fi gur e 25: M e a n (95% C.I .) l e v e l -c e s l l s of o t he f t hr ee N gr K oups at bas e lin e a nd t h e E xa m t i m e p o i n t
Fi gu re 26 s h o w s e t h c h a n g e s f -c r e o l l m p e r c b e n a t a s g e s to e th l at i at n th e E xa N m K ti me
p o i n t for i n d i vi d u al s t u d en t s in each grou p . In th e J oh rei g rou p , th ere w as a clea r i n creas in g
tren d wi th e i g h t in d ivi d u al s i n c r e a s e w d h i l th e ree s ta yed th e s am e (l es s th an 2 .6 % ch an ges : 9 9 %
Co n f i d e c n e In ter val of th e meas u re in N K -cell %). T h e r e w a s n o c l e a in r the t r Re el n axat d i on
c o n t r o l g r with o u p two in d ivi d u al s in creas ed , f o u r s t e a d y th e s a me an d fi ve d ecrea s ed . In th e
Self-h y p n o s i s , t h in r e creas e ed , f i v e s ta ye d th e s ame an d th ree d ecreas ed .
NK-cell percentage
20
15
10
5
0
N o t s i g n i f i c a n t
N o t s i g n i f i c a n t
B a s e l i n e E x a m
20
15
10
5
0
p < 0 . 0 0 1
B a s e l i n e E x a m
p = 0 . 0 2 5
N o t s i g n i f i c a n t
2 0
1 5
1 0
5
0
B a s e l i n e E x a m
Self-hy p n o s i s J o h r e i R e l a x a t i o n o n c t r o l
Fi gur e 26: The i n d i vi d u a l le ve ls of N K -c e l l p e r c e n t s a g e i t n h e t h r g e e r o u s p at ba s e lin e a nd t he Exa m
t i m e p o i n t

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
T h i s f i n d i n g w a s i n v e s t i g a t e d -to-t b y r t e h a e t a I n n a t l y e s co n i t s mp i o ari n n g p erc en tages o f
i n d i v i d u a l s b e t w e e n t h e t w o g r o -c u el p l level s s ( an d M a i n t a i n d
D e c r e a s -ce e l l d l e v e N l s . K ) All th e d at a fr om th e s u b jects wh o with d rew we re ad d ed in to th e
n u m b e r i n t h e g r o u p i n w h -cells i c [Tab h le t 1 9 h ]. e s u b j e c t s d e c
T a b l e 19: P er c enta ge s ( numbe rs ) of s u b j e ct s wh os e N K -c e l l c o u n t s m a i n t a i n e d o i r n c r e a (M s e a d i n t a i d) n e
and de c r e a s e (D d e c r e a s e ) d in t h e S e l f-hypnosis and Johrei and R e l a x a t i o on n t r c o l groups f o r the
I n t e n t -t i o o-t n r e at a na lys is ( mis s ing da t a we r e a d d e d i n t o t h e n u m the b e D r e c i r n e a s e d g r o u ) p
G r o u p Ma i n t a i n e d N -cells K D e c r e a s e d N -cells K T o t a l
Self-h yp n o s i s 4 4 % ( 7/1 6 ) 5 6 % ( 9/1 6 ) 1 6
J o h r e i 7 5 % ( 1 /1 2 6 ) 2 5 % ( 4 /1 6 ) 1 6
C o n t r o l s
3 8 % ( 6 /1 6 ) 6 2 % ( 0/1 1 6 ) 1 6
T o t a l 2 5 2 3 4 8
Th e p ercen t age of t h e s t u d en ts wh o main tain ed th e N K -cell cou n t s at th e E xam ti m e p oin t
i n t h e J o h r e i ( g 7 r 5% ) o u w p a s h i g h e r t h a n t h a t of R elax ation c o n t r o l g r o 8% u p ) ( ( 3 P e a r s ’s o n
c h i -s q u are = 4 .6 , p = 0 .0 3 3 ).
C o n c l u s i o n :
A s h as b een s h own in th e l i t e r a t u [ s r e e a l s o I n t r o d u c t i o n : 1 . 2 . 4 b. u3 t ] n ot in th is s tu d y
[3 .1 .1.4 ] , e x a m s t r e s s a to p p res e a ur lt e in d a d ecreas e in p erip h eral b lood N K -cell p ercen tage in
u n i v e r s i t y s t u d e n t i s n t h e R e l a x a t i o n c o alth n t r ou o l gh tg hr is o du ecreas p e d id n ot ach ieve
s t a t i s t i c a l s i g n i . f Ho i c weve a n c e r, t rai n in g in an d p ractis e of J oh rei re vers ed th is e f f e c t an d led to
an ove ral l i n c r e a s e
i n -c e l N l K p e r n c t a g es . In con tras t , t rai n in g a n d p r a c t i c e o f S e -h l f yp n os is d id n ot s ign ifi can tl y c h a n g e t h e -cells l . e v e l s o f N K
C D 4 -c T e l l p e r c e n t a g es
T h e r e s u l t s s h o w er e t h w a t s n o t d ih f fere n ce b et ween th e th ree gr ou p s in th e level s of
C D 4 -c T ell p ercen tages a t b a s e l i n e Self-h ( y p n o s i s a n d R e l a x a t on i o trol n c : t = 0.2, d f , = n 2 ; s 1
J oh rei an d R e l a x a t i o n c o n t r o l: t = 0.5, d f 0, = n 2 s).
R e p e a t e d m e a s u s r e AN OV A s h owed th at th ere is a tr en d toward d iffe ren ce in th e c h an ges
fro m b as el in e to th e Exa ms as s es s men t p oin t b e t w e e the n th ree gr ou p s ( F = 3 .2 , d f = 3 1 , p =
0 .0 54 ). A t t h e E x a m s p e r i o d , t h e r e -cell w a p ercen s a tage n in i th n e c Rr el e axati a s on e i n C D 4 T
c o n t r o l g r (mean o u p ch an ge = 1 .6 , t = 1 . 2 , S D = 4 . 5 , n s), d f b u t = th is 1 0 d id n ot ach ieve s t a t i s t i c a l s i g n i f i a c n a n g c e . i T n h e t c -c h ell e p ercen C D 4 tages T in th e p s ych ol ogi cal
in terven t i on gr ou p s h ad t ren d s toward s d ifferen t ch an ges f ro m th at of the R ela xatio n con t rol
g r o u p ( F 3 = . 2 , d f , p = = 3 1 0 5 . 4 0 ). T h e r as e n o w c h a n g e i n t h -cell e m p ercen e a n tage C iD n 4 T
t h e S e l f-h y p n os is gr ou p (mean ch an ge = 0 .1 , t = 0 . 1 , S D = 3 . 5 , n s), d f a = n th d 1 ere 1 was a
P h . D . a t U n i v e r s i t y o f L o n d o n - 9 8 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
t r e n d t o w da ecreas r d e in th e J oh rei g rou p (mean ch an ge = 3 .4 , t = 1 .8 , SD = 6 .2 , d f =1 0 , p =
0 . 0 9 4 ) [Tab le 2 0 a n d F i g u r 27]. e A n a l y s e s o f t h e d a t a b y g e n d e r s h o w e d t r h d e s n s a m e
[ A p p e n d i x -3 6 1 : a n -32]. T d a b A l e s A
T able 20: Me a n ( 95% C.I .) l e v e l s o -c f e l l C D 4 ( % ) t T h e S i e n l f-hyp no s is , J ohr e i a nd Re la xa t io n co ntr ol ( Contr ols) groups at b a s e l i n and e the E xa m t im e p o i n t
CD4 T-c e l l s ( % )
B a s e l i n e
E x a m s
S e l f-h y p n o s i s J o h r e i C o n t r o l s S e l f-h y p n o s i s J o h r e i C o n t r o l s
Me a n l e ve l 45.6 46.5 45.3 45.8 43.1
46.9
( 9 5 % C . I . )
n
(42.4 - 48.9)
12
(42.8 – 50.3)
11
(41.8 - 48.7)
11
(41.1 - 50.4)
12
(37.7 – 48.6)
11
(38.5 - 51.1)
11
Mean (95% C.I.) levels of CD4 T-cells (%)
5 0
4 0
3 0
2 0
1 0
0
N o t s i g n i f i c a n t
N o t s i g n i f i c a n t
p = 0 . 0 9 4
N o t s i g n i f i c a n t
N o t s i g n i f i c a n t
S e l f - h y p n o s i s J o h r e i C o n t r o l s
B a s e l i n e
E x a m s
Fi gur e 27: M e a n (95% C.I .) l e v e l s -c o e f l l s of C tD he 4 t hr T e e gr oups a t ba se lin e and t h e Ex a m t i m e p o i nt
Fi gu re 28 s h o w s e t h c h a n g e s f r o m b -c a e s l l e p l e r c i e n t e a g e s tC o D th 4 at at T th e Exa m
t i m e p o i n t f o r i n d i v i d u a ls in each gr ou p . Th ere ap p eared t o h a ve n o cl ear t ren d .
I n t h e J o h r e i g r o u p indi , v o i n d e u a l i n c r e a s , e f d i v e s ta yed th e s ame (l es s th an 2 .4 %
ch an ges : 9 9 % con fi d en t in terval of th e m eas u re in C D 4 -cell T % ) a n d f i v e d e c r e a s , e d w h i in l e
th e R el axat ion c on trol g rou p , f i v e i n d i v i d u a l s i n c r e a s e d , f o u s r t e a d y th e s am e an d t w o d e c r e a s . e d
I n t h e l e f-h y S p n o s i s g r o u , p t h r in e e creas e d , s e v e n s ta yed th e s ame an d two d e c r e a s . e d
P h . D . a t U n i v e r s i t y o f L o n d o n - 9 9 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
6 4
5 8
5 2
4 6
4 0
3 4
2 8
B a s e l i n e E x a m
6 4
5 8
5 2
4 6
4 0
3 4
2 8
B a s e l i n e E x a m
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 00 - I m p e r i a l o C n o d l o n l e g e L
6 4
5 8
5 2
4 6
4 0
3 4
2 8
B a s e l i n e E x a m
Self-hy p n o s i s J o h r e i R e l a x a t i o n o n c t r o l
Fi gur e 28: The i n d i vi d u a l l e v e l s -c o e f l l C D p e 4 r c e T n t a g t e h s e t i h n r groups e e at bas e line and t he Exa m
t i m e p o i n t
C o n c l u s i o n :
CD4 T cell percentage
E x a m s t r e s s d i d n o t a f f e c -cell t pp ercen e r ti ages p h . e In r ad a dl it ion b , nl eith o o er d of C D 4 T
t h e p s y c h o l o g i c a l i n t s e a r f f v e c e te n t d i o C n D 4 -c e T l l p e r c e n t a g e s i g n i f i c . a n t l y
C D 8 -c T e l l p e r c e n t a g es
T h e r e s u l t s s h o w er e t h w a t s n o t s i h g n i f i c a n t d ifferen ce b etween th e th ree gr ou p s in th e
l e v e l s o -c f e l l C p D e r 8 c e n t T a g e s a t b a s e l i n e ( S -h e l yp f n os is an d R e l a x a t i o n on c trol : t = 0.8, d f =
2 1 , n ; s J oh rei an d R e l a x a t i o n c o n t r o l: t = 0.2, d f 0, = n 2 s).
Th ere was n o s i gn i fi can t d i fferen ce s t a t i s t i c a l l y in th e ch an ges b etween th e th ree g r ou p s
( F = 2 .3 , d f = 3 1 , n s ). At th e E x a m t i m e p o i n ts , t h e r e w s a i g s n i f n i c o a n t c h a n g e i -cell n C D 8 T
p ercen tage in th e R e l a x a t i o n on c tr ol a n d J o h r e i g rou p s . Howe ver , an e xp lorat or y a n al ys is with
p aired t-t e s t s s h owed th at t h e C D -c 8 e l l T p e r c e n t a g e s i n c d r i e n a s t e h e S e -h l f y p n o s i s g r o u p
(mean ch an ge = 2 .5 , t = 3 . 1 , S D = 12 1 , . p 8 = , 0 . 0 d 1 f 0 ) [T = a b l e 1 2 a nd F i g u r e ]. An 2 9 al ys es o f
t h e d a t a b y g e n d e r s d h o t w h e s a m e t r e n d s [ A p p e n d i x s 6 : -3 T 3 A a b l a e n -3 d 4 ]. A
T able 21: Me a n ( 95% C.I .) l e v e l s o -c f e l l C D 8 ( % t he ) T S i e l n f-h yp no s is , J ohr e i a nd Re la xa t io n co ntr ol ( Contr ols) groups at b a s e l i n and e the E xa m t im e p o i n t
CD8 T-c e l l s ( % )
B a s e l i n e
E x a m s
S e l f-h y p nosis J o h r e i C o n t r o l s S e l f-h y p n o s i s J o h r e i C o n t r o l s
Me a n l e ve l 25.1 26.8 27.2 27.6 27.6 26.8
( 9 5 % C . I . ) (20.9 - 29.4) (24.0 – 29.6) (24.4 - 30.1) (24.0 - 31.2) (24.3 – 30.9) (23.9 - 29.8)
N 12 11 11 12 11 11

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Mean (95% C.I.) levels of CD8 T-cells (%)
3 0
2 0
1 0
0
S e l f - h y p n o s i s J o h r e i C o n t r o l s
B a s e l i n e
E x a m s
F i g u r e 29: M e a n (95% C.I .) l e v el s o f -c C e l D l 8 s of tT he t hr e e gr oups a t ba se lin e and t h e Ex a m t i m e p o i nt
Fi gu re 3 0 s h o w s e t h c h a n g e s f r o m b -c a e s l l e p l e r c i e n t e a g e s tC o D th 8 at at T th e Exa m
t i m e p o i n t f or in d ivi d u al s tu d en ts in e a c h g r o u p . I n t h e S e -h l f yp n os is gr ou p , th ere was an
i n c reas in g tren d wi th s e v e n in d ivid u als i n c r e a s , e f o d u r s ta yed th e s am e (l es s th an 1 .7 % ch an ges :
9 9 % con fi d en t in terval of th e meas u re in C D 8 -c T e l l % ) an d o n e d e c r e a s . Th e d ere was n o cl ear
t r e n in d th e J o h r e i with f o u r in creas ed , f i v e s ta yed th e s a me an d two d e c r e a s ; e d a n in d th e
R elaxat ion c on trol gr ou p s , t w o i n d i v i d u a l s i n c r e s a t s e a e d y d th , e ss a me i x an d t h r e e d ecreas ed .
CD8 T cell percentage
40
34
28
22
16
B a s e l i n e E x a m
4 0
3 4
2 8
2 2
1 6
B a s e l i n e E x a m
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 01 - I m p e r i a l o C n o d l o n l e g e L
4 0
3 4
2 8
2 2
1 6
B a s e l i n e E x a m
S e l f-hypnosis J o h r e i R e l a x a t i o n o nt c r o l
Fi gur e 30: The i n d i vi d u a l l e v e l s -c o e f l l C D p e 8 r c e T n t a g t e h s e t i h n r groups e e at bas e line and t he Exa m
t i m e p o i n t
C o n c l u s i o n :
N o t s i g n i f i c a n t
p = 0 . 0 1 0
N o t s i g n i f i c a n t
N o t -significant
N o t -significant
Exa m s tres s d id n ot ap p ear to a f f e c t p e r i p h e r -cell a l p ercen b l to ages o d . H C o w D e 8 v e r , T
t h e S e l f-h y p n o s i s a p p e a r e d t o i n c r C e a D s 8 e -c e T l l p ercen ta ges .

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
S u m m a r y :
Pr a c t i s i n g S e l -h f yp n os is or J oh r ei p ri o r to acad emic e xa ms , wh en co mp ared with th e
p a s s i v e r e l a x a t i o n e x p e r i e n c e , d i d n o t a p p e a r t o a f f e c t p e r c e i v e d in s t ur ne ivers s s l ie t y v e l s
s tu d en ts faci n g acad emi c exa ms . J o h r e i , h owever , a p p e a r e d t o d e c r e a s e i t n h c r e e a sed a n x i e t y
l e v e l s i n u n i v e r s i t y s t u d e n t s f a c i n g a e t x a m a c s. a d e m i c
N K C A l e v e l s i n t h e u n i v e r s i t y s t u d e n t s p r a c t i s i n g e i t h e -h r yp S e nl f os is or J oh rei at
a c a d e m i c e x a m s w e r e s i m i l t a r h e t l o e v e l t s h e i s n t u s d f e o l n l o w i n g t h e c o n tr o l rel axation
e x p e r i e n c e s. O n t h e o t h e r h c a a n d e , m i a c e x a m s tr e s s ap p eared to b e as s ociated wi th a d ecreas e
i n -c e N l K l l e v e in l s u n ivers it y s tu d en t wi th relaxati on exp erien ce alth ou gh th is d ec reas e d id n ot
a c h i e v e s t a t i s t i c a l s i g , n i f a i n c d a n c i e n t e gl r y e th s t is i d n e c r e a s e w a s er rs e ed v in th e s tu d en ts t r a i n in e d a n d p r a c t i s i n g oh J r e i . S e l f-h yp n os is d id n ot ap p ear to d iffer s i gn ifican tly f ro m
Relaxat ion c on trol in th e e ffect on N K -c e l l l e v e . l O s n t h i s o c c a s i xam o n , se tres s w as n ot fou n d
t o a f f e c t th e le vel s o f C D 4 a n d -cells, C D 8 a n d T th e level s of th es e cells were n ot affected b y
J o h r e i i n t e r v wh e n ile t i Se o n l f-h y p n o s i s i n c r e a d s e C D 8 -c e T l l p e rcen tages wh en s tu d en ts faced
a c a d e m s. i c e x a m
T h e s e f i n d i n g s p a r t i a l l y s u p p o r t e d t h e h y p o t h e s i t s e r v t e h n a t n t i ma o p y s y c h o l o g i c a l i n
c o u n t e r a c t t h e f f e c t o f s t r e s s u p o n t h e p r o p o s e d -n e i u n r t o-e e n g d r o a c t r i e n o d -i mp s mu y c nh e o
n e t w o r k ; a n d w a r r a n t t h e n e e d t o i n v e s t i g a t e t h i s h y p o t h e s i s f u , r in t h a e r p a t i e n t p o p u . l a t i o n
H e n c e , t h e n e x t s t u d y e m p l o H y s I -i n V f e c t e d i n d i v i d u [ a 3 l . s 2 ].
3 . 2 T h e i n f l u e n c e o f p s y c h o l o g i upo c a l n per i ce n t i ve e r d v str e n e t ss i a nd o n
q u a l i -o t y f -l i f e a n d v a r i o u s i m m u n o l o g i c a l -a d sso i s e cia a s te e d pa ra me te r s i n
H I V-i n f e c t e d i n d i v i d u a l s
T h e o b j e c t i v e o f t h i s s t u d y w a s t o d e t e r m i n e i f t h e ot f r pa si ych n i n ol g ogi a n cal d p r a c t i c
s t r e s s c o p i n g s k i l l s w o u l d i n f l u e n c as e well s t r as e s i mmu s p ne ol r c o e gi p cal t i po ar n ameters
p a r t i c u l the a r l d i y s e a s e p r o g r e s m s a i r e o k r n , C D4 T-c e l l c o u n , t s i n -in fected H I V in d ivi d u al s .
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 02 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
3 . 2 . 1
Di s e a s e-a s s o c i a t a e n d s t r e s s-rel a te d c ha ng es i n -in H I fecte V d i n d i v i d u a l s
Th is p a r t i n v e s t i g a t e s t h e p r o p o s e d i -n n t e u e r g o-e r a n t d o e c d r i p s n -im o y c mu h o n e n et wor k
b y e xa mi n in g p s ych ol o gi cal an d i m m u n e ( d i s e a s e ) p a r a m e t e r s a n d a s s o c i a t i o n s b e th t e w e e n
p a r a m e t e r s, i .e. b et ween th e l e v e l s o f st r e s s p e r c e p t ion an d p erceived q u a l i -o t f y -l i f e a n d C -D
4 T
c e l l c o u n t a s s p r i m a r y o u t c o m e m e a s . u r e s
3 .2 .1 .1 P s ych ol o gi cal p r ofi les of th e H I V-i n f e c t e d i n d i v i d u a r l s e c r u i t e d i n t o t h e s t u d y
T h e -i H n I f e V c t e d i n d i v i d u a l s r e c r u i t e d i n t o t h e s t u d y w e r fou e r a s k e d a t r e c r u
m o n t h s l a t e r t o c o m p s y l c e h t o l e o g t i c h a e l q p u e s t i o n n a i r e l s i s t in e ord d er t b o e a s l s e s o s th w ei r
l e v e l s o f st r e s s p ercep ti on an d p erceiv ed q u a l i -o t f y -l i f e :
Ge n e r a l a n d -i H n I f e V c t i o n r e st l r e a s t s p e d r c e p t i o n
P e r c e i v e d S t r e s s o r e S c ( P S S ) : s e c o n d a r a y i s a l p p s c a l e
State an xi et y in th e St at e T r a i t A n x i e t y I n v e n t o r y ( S T A : I ) a n x i e t y s c a l e
I m p a c t E v e n t S c a l e ( IE S ) : p r i m a r y a p p r a i s a l a g a i n s t a s t r e s s o r s c a l e
Q u a l i -o t f y -life ( Q o L ) p e r c e p t i o n
Lo c u s o f C o n t r o l ( Lo C ) : s en s e of takin g c o n t r o l o f o ’s n e o w n l i s ca f e l e (recal l :
in n er o r o u t e r l o c u s o f c o n t r o l = l o w o r h i g h s c o r e )
M e n t a l C o m p o u n m e m n t a r y S i n t S h F e -3 6 ( M C S ) : m e n t a l -o q f u -l a l i f i e t y s c a l e
P i t t s b u r g h S l e e p Q u a l i t y I n v e n t o r y ( P S Q I ) : s l e e p q u a l i t y s c a l e
W i t h ll a o f t h e s e q u e s t i o n n a i r e s , e x c M e p C t S, lo t w h e r s c o r es m e a n b e t t e r fu n c t i o n i . n g
A n a l y s e s o f t h e s e d a t a i n v o l v e d irs , t, f a c omp ari s on of th e P SS an d th e State an xie t y s co res o f
th e p art i ci p an t s i n t h is s t ud y with th os e of th e u n ivers it y s tu d en t s in th e p reviou s s tu d y. Sec on d ,
t h e o t h e r p s yc h o l o g i c a l p r ofi les c ollected s p ecificall y to th i s s tu d y we re an al ys ed b y c o m p a r in g
t h e t w o s t r -r e s e s l a t e d s u b g r o u p s lab ( elled as N o t -s tr es s ed a n d S t r e s s s e d u b g r o u p s ) d e f b y i n e d
t h e m i d l i n e s p l i t o f t h e P S S a t r e c r u i t m e n t , i . e . i n d e i Pv SS i d were u a l s s c o r i n g m o r
p laced in th e S t r e s s se ub d grou p an d in d ivi d u al s s corin g eq u al to o r b elow 3 1 were p laced in to
th e N o t -s t r e s s se ud b grou p .
P ercei ved stres s l e v e l s ( P S S )
T h e -in H fected I V in d ivi d u al s h ad h igh er P SS s cores (mean d iffe ren ce = 7 .2 , t = 4 .5 , d f =
8 1 , p < 0 . 0 0 1 ) t h a n th e u n i v e r s i t y s t u d e n t s f a c i n g e x a m i n a t i o n s , a n d th e P S S s c o r e s d n i ot d
ch an ge s ign ifi can tl y ( F = 2, 0 . 0 d f = , n 4 s) 6 f recru r o it m en t to th e f ou r mon th s later time p oin t
i n -in H fected I V in d ivi d u al s [T a b l e 1].
2
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 03 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
T able 22: Me dia ns , me a ns and st a nda rd de viat io ns of th e P SS of t h e u n i v e r s i t y s t u d e -exam n t s and a t n o n
e xa ms a nd of t h e -i n H f I e c V t individuals e d a t re cr uit me nt and f o u r m o n t h s l a t e r
U n i v e r s i t y s t u d e n t s
H I V-i n f e c t e d i n d i v i d u a l s
Non-e xa m E x a m s R e c r u i t m e n t A f t e r 4 m o n t h s
M e d i a n
22 25 32 31
M e a n 23.3 24.4 31.6 31.7
S D 8.8 7.5 7.0 5.6
n 34 32 51 51
C o n c l u s i o n :
P atien ts wi t h HIV h ave h i gh er s tres s p erc ep tion th an u n ivers it y s tu d en t s facin g exa ms .
Th e s u b grou p s of N o t -s t r e s s an e d S t r e s s e w d e r e d e f i n e d b y t h e j u d g e m mi e n dt lin o e f a
s p l i t o f t h e P S S s c o r e a t r e c r u Si tr t es m se ed n t s . u b T g h r e o u p h a 26 d s ub ject s (i n cl ud in g two females ) a n d t h N e o t -s t r e s s e s d u b g r o u p h 2a 5 d s ub ject s (on e femal e). Th e res u lts f rom 5 1
s u b j e c t s ( t h r e e f e m a l e s a n d 4 8 m a l t e s s ) f r o a m n d 4 8 t h m s e u a b l r j e e c s t u s o n rl e y s imil a ar an d
t h e y h a v e t h e s a m e t r e n d , s o r o e n s l u y l t s h e f r o m 4 8 m a l e s re u b pj res e c en t s ted a .
T h e r e s u l t -i n f e r c t o e m d m 4 a l 8 e i H n I d i V v i d u a l s er s e h o w e s r e t d i h f a f t e r e t n c h e s
b etween th e S t r e s s a e n d d N o n -s t r e s s e u d bgr o u p s i n t h vels e l e o f P SS at recru it m e n t an d fou r
mon th s l at er [ Tab l e 23].
T able 23: Me a n ( 95% C.I .) l e v e l s o f t h e the P S Not-s S i t n r e s s e d a n d S t s r u e bgr s s oe ud ps a t the
r e cr u i t m e nt and f o u r m o n t h s l a t e r
P S S l e v e l s
R e c r u it m e n t A f t e r 4 m o n t h s
Not-s t r e s s e d St re s se d Not-s t r e s s e d St re s se d
Me a n s c o r e 26.0
36.8
27.4
35.5
( 9 5 % C . I . ) (24.6 – 29.5) (34.9 – 38.6) (25.8 – 28.9) (33.2 – 35.5)
n 24 24 24 24
Th e r e e r e s i g w n i f i c a n t d i f f e r e n s c be etween th e two s u bgrou p s b oth at r e c r u i t m e n t t ( = 9.2 ,
d f = 4 6 , p < 0 . 0 0 1 ) a n d f uo r m o n t h s l a t e r (t = 5.9, d f 6, = p < 4 0 . 0 0 1 ). T h e r e w a s s ign a ifi can t
time x s u b g r o u in p teract ion ( F = 5.8, d f 9, = p 4 = 0 . 0 ), 2 b 0 u t th e P SS s cores d id n ot ch an ge
s ign ifican tl y o ver th e fou r m on th s s tu d y p eriod in th e No t -s t r e s s (t e d = 1.2, d f = 2 3 , n s) or in th e
S t r e s s su e d b grou p (t = 1 .6 , d f , = n 2 s) 3 [Fi gu re 31].
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 04 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Mean (95% C.I.) PSS levels
4 0
3 0
2 0
1 0
0
N o t - s t r e s s e d S t r e s s e d
R e c r u i t m e n t
A ft er 4
m o n t h s
Fi gur e 31: M e a n (95% C.I .) P S S l e v e l of s the Not-s tr e ss e d and S t r e s s se ubgr d oup s at r e cr uit me nt and
f o u r m o n t h s l a t e r
C o n c l u s i o n :
P S S l e v e l s
i n -i n f H e I c t e V d i n d i v i d u a d l i s d n o t ge c h sa ign n ifi can tl y ove r th e f ou r mon th s
o f t h e s t u d y , p an e d r th i o is d con s is ten c y i n th e levels of P SS s cores w a s a l s o s h w o h w e n th e
S tr es s ed o r N o t-s tr es s ed s u b g r o u ps w e r e s e p a r a t e l y . c o m p a r e d
Sta te a n x i e t y l e v e l s
I n c o n t r a s t t o t h e P S S , a n x i t e t h y e -i n l f e c H v t e I e l d s V i n d i n v i d u a l s w e r e s i m i tl o a r th e
levels o f th e u n ivers it y s tu d en ts ( m e a n d i f f e ren ce = 1 .1 , t = 0 . 4 , d , f n = s) , 8 5 a n s d t a t an e xiet y
l e v e l i -in fected n t in h d ivi e d u al H s I d id V n ot ch an ge s ign ifican tl y ( F = 0 . 7 , d , f n s) = fro m 4 6
recru it men t to f o u r m o n t h s l a t e [T r a b l e 4]. 2
T able 24: M e d i a n , m e a n a n d s t a n d a r d d e v i a t i o n o f a n t x i h e t S y t a s t c of o e r t e h e u n i ve r s i t y s t u de nt s at
non-e xa m an d e xa ms and of t h e -i n H f I e c V t individuals e d a t rec r uit me nt a nd f o u r m o n t h s l a t e r
U n i v e r s i t y s t u d e n t s H I V-i n f e c t e d i n d i v i d u a l s
Non-e xa m E x a m s R e c r u i t m e n t A f t e r 4 m o n t h s
M e d i a n
37 40 36 38
M e a n 37.9 39.7 38.9 40.8
S D 9.4 8.3 12.5 14.4
n 37 36 51 51
C o n c l u s i o n :
N o t -significant
p < 0 . 0 0 1
p < 0 . 0 0 1
N o t -significant
T h i s r e s u l t s u g g e s t e d t h a t th ere was little d i f f e r e n c in e th e St at e an xi et y s c o r es in H IV-
i n f e c t e d i n d i v i d u a l s c o m p a r e d w u n i t v h e r s t i h t e y s t u d e facin n t s g acad emi c exa ms .
W h e n c o m p a r i s o n s w e r e m a d e b e t w e e n 4 t 8 h e -in H fected I V mal e in d ivi d u al s in the N o t -
s tr es s ed and S t r e s s grou e d p s b as ed on a med ian s p lit of t h e P S s S c o r , e t h e i n d i v i d u a l s in th e
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 05 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
S t r e s s su e d b grou p h ad s ign ifi can tl y h igh e r an xiet y lev els th an th e in d ivid u als in th e N o t -
s t r e s s e u d b g r o u p b o t h a t r e c r u i t m e n t t = ( 7 .0 , d f = 4 9 , p < 0 . 0 0 1 ) a n d f o u r m o n t h s l a t e = r ( 6 .1 ,
d f = 4 9 , p < 0 .0 0 1 ). Th ere was n o s ign ific an t time x s u b g r o up i n t e r a c t i o n .7 , ( F d f = , = 1 n s 4 ), 9
a n d th e St at e an xi et y s c o r e s d i d n o t c h a s n g i e g n i f i c a o n v t e l r y t h e s t u d y in p th e r No i o t d -
s tr es s ed su b grou p (mean ch an ge = 2 .2 , t = 1 . 1 , d , f n = s) or 2 in 3 th e S t r e s s se ud b grou p (mean
ch an ge = - 0 .3 , t = 0 . 3 , d , f n s) = [ 2 T 3 a b l 5 e a 2 n d F i g u r 32]. e
T able 25: Me a n ( 95% C.I .) l e v e l s o f t h e S t a t e a n x i e t y s c o the r e Not-st o f re t sh se e d and S T A S I t r i e n s s e d
subgr ou ps at t h e r e cr u i t m e nt and f o u r m o n t h s l a t e r
St a t e an xie t y s c o r e o f t h e S T A I
R e c r u it m e n t A f t e r 4 m o n t h s
Not-s t r e s s e d St re s se d Not-s t r e s s e d St re s se d
Me a n l e ve l 30.2
49.6
30.5
47.4
( 9 5 % C . I . ) (26.9 – 33.4) (45.1 – 54.1) (27.6 – 33.3) (42.6 – 52.2)
n 24 24 24 24
Mean (95% C.I.) State anxiety scores
6 0
5 0
4 0
3 0
2 0
1 0
0
N o t - s t r e s s e d S t r e s s e d
R e c r u i t m e n t
a fte r 4
m o n t h s
Fi gur e 32: M e a n (95% C.I .) le ve ls of t he St a te a nx iet y s c or e s in t he ST AI of t he N ot -s t re s s e d and S t r e s s
subgroups at re c ruit me nt a nd f o u r m o n t h s l a t e r
C o n c l u s i o n :
N o t -significant
p < 0 . 0 0 1
p < 0 . 0 0 1
N o t -significant
H I V-in fect ed in d ivi d u al s rep ortin g l ow le vels o f stre s s a l s o r e p o r t l o w e r s c o r s e of t h e
State an xi et y t h a n i n d i vi d u al s rep ortin g h igh levels of s tr es s .
P rima ry a ppra i s a l a g a i n s t a s pecific lif e even t l e v e l s ( I E S )
T h e p r i m a r y a p p r a i s a l -in o fe f cti on t was h e meas a u red w a b y r th e n e s s o f c
IES. Th e m e a n I E S s c o r e s o f S t r h e s s in e d ivid u al s were s ign ifi can tl y h igh er th a n th e levels
fo r th e N o t -s t r e s s e i d n d i v i d u a l s itment a t r e (t c = r 3.2, u d f = 2 3 , p = 0 . 0 0 3 ) an d aft er f ou r m on th s
(t = 3.2, d f = 2 3 , p = 0 . 0 0 3 ). T h e I E S s c o r e s d e s c i r g e n a i s f e i d c ove a n t r th l y e s tu d y p eri od ( F =
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 06 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
1 8 .8 , d f = 4 6 , p < 0 . 0 0 1 ), a n th d is was o b s e r v ed i n b o th t e h S tr es s ed s ub grou p (me an ch an ge =
7.3, t = 3 .5, d f = 2 3 , p = 0 . 0 0 ) 2 a n d th e N o t -s t r e s s e s d u b g r o u p ( m e a n 6.2, c h t a = n 2.7, g e d f =
2 3 , p = 0 . 0 1 ), 3 b u t th ere was n o s ign ifi ca n t time x s u b g r ou p i n t e r a c t i 0 o .5 n , ( d f F , = n 4 s ) 9
[T a b l e 6 2 a n d igu F re 33].
T able 26: Me a n ( 95% C.I .) l e v e l s o S f i the n t subgr h e ou I pE s of t he Not-st r es s ed a nd S t r e s s at e d t he
r e cr u i t m e nt and f o u r m o n t h s l a t e r
I E S
R e c r u it m e n t A f t e r 4 m o n t h s
Not-s t r e s s e d St re s se d Not-s t r e s s e d St re s se d
Me a n 16.5
31.4
10.4
24.2
( 9 5 % C . I . ) (10.0 – 23.1) (24.7 – 38.1) (5.9 – 14.8) (16.6 – 31.7)
n 24 24 24 24
Mean (95% C.I.) IES levels
4 0
3 0
2 0
1 0
0
N o t - s t r e s s e d S t r e s s e d
R e c r u i t m e n t
A fter 4
m o n t h s
Fi gur e 33: M e a n (95% C.I .) le ve ls of t he I ES in t he N ot -s t r e s s and e d S t r e s s subgroups at r ec r uit men t and
f o u r m o n t h s l a t e r
C o n c l u s i o n :
p < 0 . 0 0 1
p = 0 . 0 0 3
p = 0 . 0 0 3
p = 0 . 0 0 2
T h e i m p a c t i n t h p e r i m a r y a p p r a i s a l f r o m d i a g n o s e d a s
c a r r y -i i n f n e c g t i o n H I d e as c V r ed e
o v e r t h e s t u d y . Alth p e r ou i o gh d th e d ecre as ed levels o f imp act in th e H I V-in fected in d ivid u als
w e r e n o t d i f f e r e n t th e b se tres t w se ed e n a n d n o t-s tres s ed s u bg r o u ps, i n d i v i d u a l w s i t h a h i g h
p e r c e i v e d s t r e s s l e v e l c o n s i s t e n t l y s h o w e d h i g h e r l e v e l s i o m f p act th an th e in d ivi du al s in th e
n o t -s t res s ed s u bg r o u p b ot h at r e c r u i t m e n t a n d f o u r m o n t h s l a . t e r
L ocus of con trol (L oC : S e n s e o f c o n t r o l o f ’s o n w e n l i f e l e ) v e l s
Th e s en s e of ta ki n g c on trol of o n e ’s o w n l i was f e meas u red b y u s in g th e LoC . Th e Lo C
s c o r e re e s ign ifi w can tl y h i g h e r i n S t h r e e s s in e d ividu al s th an th e N o t -s t r e s s ind e d ivid u al s at
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 07 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
recru it men t (t = 2.8, d f = 2 3 , p = 0 . 0 ) 0 an 7 d fou r m on th s lat er (t = 1.0, d f = 2 3 , p = 0 . 0 0 ), 2 b u t
th ere was n o s ign ifi can t time x s u b g ro up i n t e r a c t i o n ( F 4 9, = n s ), 0 . an 1 d , th e sd cores f = d id n ot
c h a n g e s ign ifi can tl y ove r th e s tu d y p eri o d ( F = 0 . 4 , d , f n s) = [ T 4 a 6 b l e 2 a 7 n d F i g u 4]. r e 3
T able 27: Me a n ( 95% C.I .) l e v e l s o f t h e the L o N C ot -s i tr n e ss e d and S t r e s s subg e d r o u p s a t t he
r e cr u i t m e nt and f o u r m o n t h s l a t e r
Lo C s c o r e
R e c r u it m e n t A f t e r 4 m o n t h s
Not-s t r e s s e d St re s se d Not-s t r e s s e d St re s se d
Me a n l e ve l 9.3
12.6
8.7
12.6
( 9 5 % C . I . ) (5.9 – 14.8) (11.0 – 14.2) (7.5 – 11.0) (11.0 – 14.2)
n 24 24 24 24
Mean (95% C.I.) LoC levels
1 5
1 0
5
0
N o t - s t r e s s e d S t r e s s e d
R e c r u i t m e n t
A fte r 4
m o n t h s
Fi gur e 34: M e a n (95% C.I .) l e ve l s o f t h e Lo C i n the N ot -s t r e s s and e d S t r e s s subgroups e d a t r e cr uit ment
and f o u r m o n t h s l a t e r
C o n c l u s i o n :
N o t -significant
p = 0 . 0 0 7
Th e locu s of con t r ol d i d n ot ch an ge s ign if ican tl y o ver th e s tu d y p eri od , an d les s s t res s ed
H I V-i n f e c t e d i n d i v i d u rep a l s orted th e lo wer s co res (a h igh er s en s e of t a k i n c g o n t r o l o f o ’s n e
o w n l i ) f th e an d id h igh er s t r e s s e d i n d i v i d u . a l s
N o t -significant
p = 0 . 2
0 0
M enta l a s p e c t o f q u a l i t y o f l i f e l e v e l s ( M C p S s : y c h o l o g i c a l f u n c t ) i o n i n g
T h e p s ych ol ogi cal fu n ct i on i n g in th e H I V-i n f e c t e d i n d i v i d u a l s n o t r e c e i v i n g a n t i-
r e t r o v i r a l m e d i c a t i o n a n d n o t e x i p e r n c i n g d i s e a s -related e s ym p to ms in th is s tu d y was
examin ed b y meas u ri n g m en tal as p ect of q u alit y of lif e, i.e . th e MC S s c ores . Th e M C S s c o r e s
w e r e s i g n i f i c a n tl y h i gh er in th e N o t -s tr es s ed i n d i v i d u a l s t h a n S i t n r t e s h e s in e d ivid u al s at
recru it men t (t = - 5.8, d f = 2 3 , p < 0 . 0 0 1 ) a n d f o u r m s o later n t h (t = - 4.6, d f = 2 3 , p < 0 .0 0 1 ),
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 08 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
b u t th ere was n o s ign ifi can t time x s u b g r o u p i n t e r a c t i o n .2 , ( F d f = = , 1 4 n 9 s ) , th e a n s cores d d id n ot ch an ge s ign ifi can tl y ov er th e s tu d y p eriod ( F = 0 .8, d f , = n 4 s) 6 [ T a b l e 28 an d Fi gu re 35].
T able 28: Me a n ( 95% C.I .) l e v e l s o f t h e the M C N S ot -s i tr n es s ed and S t r e s s subgr e d ou ps a t r e cr u i t m en t
and f o u r m o n t h s l a t e r
M C S s c o r e
R e c r u it m e n t A f t e r 4 m o n t h s
Not-s t r e s s e d St re s se d Not-s t r e s s e d St re s se d
Me a n 51.8
35.3
52.1
37.6
( 9 5 % C . I . ) (48.7 – 54.8) (30.5 – 40.1) (48.8 – 55.4) (32.2 – 42.9)
n 24 24 24 24
Mean (95% C.I.) MCS levels
6 0
5 0
4 0
3 0
2 0
1 0
0
N o t - s t r e s s e d S t r e s s e d
R e c r u i t m e n t
Af te r 4
m o n t h s
Fi gur e 35: M e a n (95% C.I .) le ve ls of t he M SC in t he N ot -s t r e s s and e d Str e ss e d subgroups a t r e cr uit me nt
and f o u r m o n t h s l a t e r
C o n c l u s i o n :
P s y c h o l o g i c a l f nu in n c g, t as i o meas u red b y th e men tal h e a l t h c o m p o n e n t -3 6 o f t h e S F
( M C S ) , d id n ot ch an ge s i gn ifican tl y o v e r t h e s t u -in d fected y p in e d ir vi di u al o s d in , th e a n d H I V
s tres s ed s u b grou p r e p o r t e d l o w e r l e v e sl ych s olo o f gi cal p fu n ct ion in g th an in d ividuals in th e
n o n -s t r e s s e d s u b g r o u p b a o t r h e c r u i t m e n t a n d f o u r m o n t h s l a . t e r
Sleep q u a l i t y l e v e l ( P s S Q I )
Th e P SQI s co res of th e S t r e s s in e d ivid ual s were s ign ifi c an tl y h igh er th an th at o f t h e N o t -
s t r e s s at e d recru it men t (t = 2 .1 , d f 6, = p 4 = 0 . 30 9 ) an d aft er f ou r m on th s (t = 2.9, d f 6, = p = 4
0 . 0 05), b u t th ere was n o s ign ifican t time x s u b g r o u p i n t e r a c t i o n , ( F d f = 9, = 0 n. s 4 6 ), an d th e
s cores d id n ot ch an ge s i g n i f i c a on ver t l ty h e s tu d y p eri od ( F = 0 .6, d f , = n 4 s) 6 [ T a b l e an 2 9 d
F i g u r e 6]. 3
N o t -significant
p < 0 . 0 0 1
N o t -significant
p < 0 . 0 0 1
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 09 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
T able 29: Me a n ( 95% C.I .) l e ve l s o f t h e P t he S Q N I ot -s i tr n es s ed and S t r e s s subgr e d ou ps a t r e cr u i t m en t
and f o u r m o n t h s l a t e r
P S Q I
R e c r u it m e n t A f t e r 4 m o n t h s
Not-s t r e s s e d St re s se d Not-s t r e s s e d St re s se d
Mea n
8.1
10.3
7.5
10.2
( 9 5 % C . I . ) (6.9 – 9.4) (8.7 – 11.8) (6.6 – 8.4) (8.6 – 11.8)
n 24 24 24 24
Mean (95% C.I.) PSQI scores
1 2
1 0
8
6
4
2
0
N o t - s t r e s s e d S t r e s s e d
R e c r u i t m e n t
A fter 4
m o n t h s
Fi gur e 36: M e a n (95% C.I .) le ve ls of t he P SQI in t he S t r e s s and N ot -s t r e s s e s u d b g r o u p s a t re c r uit me nt
and f o u r m o n t h s l a t e r
C o n c l u s i o n :
p = 0 . 0 3 9
N o t -significant
N o t -significant
p = 0 . 0 0 5
Th e s leep q u al it y s c ores d id n ot ch an ge s i gn ifican tl y o v e r t h e s t u -d
y p e r i o d ,
in fected i n d i vi d u al s in t h e s t res s ed s ub grou p r e p o r t e d wo rs e s leep q u alit y th an H I V-in fe cted
i n d i v i d u a l i s n t h e -s n t o n r e s s e d s u b g at r recru o u p it men t an d f ou r m on th s later.
3 .2 .1 .2 St r e s s-r e l a t e d p e r c e an p t d i d i o s n e a s e p r o g r e s s i o n m a r k e s r o f H I V i n f e c t i o n
C D 4 -c T ell c ou n ts an d HIV vi ral l oad lev els are r ou tin el y m eas u red f o r t h e p u r p o s e o f
c l i n i c a l m l o y n i t o r i n g d i s e a s e p r o g r e s s i o n . T h e r e -cell f o r e , r e l a t i o n
c o u n t s a n d H I V v i r a l l o a d l e v e l s a n d l e tres v e l s s p erc o f ep s ti on were exa mi n ed .
R a t e o f d e c l -c i e l n l e c o u n i t ( n C D 4 C g D r 4 a d i e T n t )
C D 4 -c T e l l c o u n t s f o r m a m a j o r -in fected p a r p a t ti en ts o . f t h e r o
A s d e s c r i b e d i n t h e m e t h o d s s e c t i o n [ 2 . 6 3 1 . p 2 a ] r , t i o c nts f i p t a r h e c r u i , on t e l y d 3 8 p at ien ts ( 6 0 ) h . a d 3 s u f % f i c ie n t d a t a f r o m w h 4 i g rad c ih en ts dt u ri o n g th c e (fou a l r c mon u th l a t e t h e
p l u s o n e m o , n five t h m on th s al toget h er, i . e. B as elin e to T erm f ou r) s tu d y p eriod . W i t h i n t 38 h e
p atien ts , 3 2 p art i ci p an t s (3 0 males an d two fe males ) co mp leted th ei r q u es tion n aires. Th e res u lt s
ob tain ed from 3 2 s u b j ect s and th e res u lts fro m 3 0 male s u b ject s on l y are s i milar an d th e y h a ve
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 10 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
th e s ame t ren d , s o on l y t h e res u lts fro m 3 0 male s u b jects were p res en ted . Mean C D4 grad ien t of
3 0 mal e s u b j ect s was a d ecl i n e of 3 cells p er l p er mon th .
Th e C D 4 grad ien t o ver th e five m on th s w a s i n v e s t i g a t e d b y c o r r e l a t i o n a n a fo l r y s e s
a s s o c i a t i o n with s the l e v e l s o f s t r h e s -r s elated p ercep ti on s (S tat e an xiet y s co re of th e STAI,
th e Percei ved St res s Sc o r e: PSS a n d I m p a c t E v e n t S : c I a E l S) e an d the p e r c e i v q e u d a l i -o t f y -life
(Locu s of Co n t r o l : L o , C M e n t a l C o m p o n e n t S u m m a -3 r 6 y : M i C S n an t d h P e it ts bS uF rgh Sl eep
Q u a l i t y I : n P d S e Q x I ). Th e C D 4 g r a d i e n t s o v e r t h e f i v e m o n t h s n w o t a s s i g n i f i a c s a s n t o c l i y a t e d
with th e s cores o f St at e an xi et y, I E S o r P S S a t e i t h e r re cru itmen t o r a f t e r t h fe ou r mon th s ti me
p o i n t s, a n d t h a t t h e r e w a s n o s i g n i f i c a n t a s s with o c i a t s i c o n r e s o f th e M C S o r P S Q I a t e i t h e r
recru it men t o r a f t e r f o u r m o n t h s Ap [ p e n d i x 6 : T a b l -3 e 5 ] . here A T was a tren d tow ard s a
p o s i t i v e c o r ti r on e l (r a = 0 .3 2 , n = 3 0 , p = 0 .0 85 ) b etween th e C D4 grad ien ts an d Lo C s cores at
recru it men t , b u t t h i s rel at i on s h ip was n ot s tatis ticall y s ign ifican t at f ou r mon th s aft er th e
r e c r u i t m e n t [Ap p e n d i x 6 : Ta b l -3 e 5 ]. A
C o n c l u s i o n :
Th e s c o r e s o f s t r e s s , p q e u r a c l e i p t y i o o n f l i f e q u a n l d i eith s t l y er e e at p re cru it men t or at
fou r mon th s h a d n o s ign ifi can t a s s o c i a t ion w i t h t h e C D 4 g r a d i over e n t s th e fi ve m on th s p eri od ,
i.e. n o n e o f t h e s c o r e a s t a o n e a s s e s s m e n t p o i n t c o u i l n d t b h e i s u s e s pd t red u t d ict y o or to indicat e th e r a t e o f c h a n g e i n t n h t s e C i D n 4 -in c fected o H u I V p at ien ts n o t r e c e i v i n g a n t i-
retro viral t reat men t .
T h e D 4 C g r a d i e n t r e p r e s e n ts t h e r a t e o f c Ch D4 a n g cou e ni ts n o v e r a f i v e pm eriod o n t , h
t h e r e f o r e c h a n g e s c o r e s o f vari t h ou e s p ercei ved s tres s sc a les (State an xiet y s co res , P SS and
IES) ove r th e s am e p eri od we re a n a l y s ed with th e C D 4 g r a d i e n t. Th e C D 4 g r a d i e n t s h a d n o
s i g n i f i c a n t a s s o c iation wi t h th e State an xi et y, I ES or P SS [Ap p e n d i x 6 : Tab le A-3 6 ].
Fu rth er, c h a n g e s c o r e s o f t h e v a r i o u q s u a l p e i r -o t c f y -l e i v f e d e w e r e a n a l y s i e t d , w a s a n d
fou n d th at th e C D 4 g r a d i e n t s h a d a s i g n i an f i t c n egat ive c or rel at ion with th e ch an ge s cores of th e
L o C; an d a s ign ifi can t p o s i t i v c e o r r e l a t ion with th e ch an ge s cores o f th e M C S , while t h e r e w a s
tren d toward s a n egat i ve c o r r e l a t with i o n the c h a n g e s c o r e s o f P t S h Q e I [T a b l e 3 0].
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 11 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
T able 30: C o r r e l s a t b e i t o w n e e n t h e C D 4 g r a d i e n t per ( c e l l s pe r m o n t h ) a n d t h e c h a s n c g o e r e s of
pe r ce ive d q u a l i -of-l t y i f e a s l c es i : n
L o C * M C S * P S Q I
R - .40 .44 - .32
2-t a ile d p 0.029 0.015 0.086
N 30 30 30
*: p < 0.05
Th e cor rel at i on s b et ween C D4 gr ad ien t an d th e c h a n g e s c o r e s in th e (1 ) LoC , (2 ) MC S
an d (3 ) P S QI can i m p l y t h a t :
1. In d ivi d u al s wi th an i n c r e a sed s en s e of tak in g c o n t r o l o f o ’s n e o w n l i (d f ecreas e ed
t h e i r sc o r e L s) o sC h ow ed an in creas e in t h e i r -c C e D ll 4 c ou nT ts (recal l th at l ow LoC
= i n n e r l o c u s o f c o n t r o l), a n d i n d i v i d u a l s w h o d e c r e s a s e n d s e t h o e f n trol c o
(in creas ed th ei r LoC sc o r e s) s h owed a d e c r e a s e in t h e i r -c e C l l D c 4 o u n t T s ;
2 . I n d i v i d u a l s im w p h r o o v e d t h e i r p s ych ol o gi cal fu n ction in g (in cre as ed MC S levels )
s h o w e d a n i n c r e a s t e h i e n i r -cell C D c ou 4 n tT s , an d in d ivi du al s wh o rep orted a
d e c r e a s e p i s yc n h o l o g i c a l fu n ct ion in g (d e creas ed MC S s c o r es ) s h owed a d e c r e a s e i n
t h e i r -c C e D l 4 l T c o u n t s ; a n d
3. I n d i v i d u a l s im w p i r t o v h em e n t their i n s le ep q u al it y (d ecr eas ed P SQI s c o r es ) s h ow ed
a n i n c r e a s e t i h n e i r -c e C l l D 4 c o u n T t (re s call th at l o w P S Q I = b e t t e r s l e e p ), q u a l i t y
an d in d ivi du al s wh o r e p o r t e d a d e c r e s leep a s e q ui al n it y (i n creas ed P SQI s c o r es )
s h owed a d e c r e a s e in t h e i r -c ell C D co 4 u n tT s .
Th erefo re, fu rt h er an al ys es we re p er for m ed after gr ou p in g th e p atien ts accord in g to
ch an ge sc o r e s o f s t e h p e e r c e i v e d q u a l i ty-o f -l i f e s c a l e ( s i n c r e a s e d o r d e c r e a s e d ), a n similar d
t r e n s d o f a s s o c i a t i o n b s e t w e e n c h a n g e s i n t h e s e s c a l e s C D a n 4 d g r t a d h i e n ts were
d e m o n s t r a t . T e h d e r e w e r e s i g n i f i c a n t d i th f e f C e D r 4 e g n r c a e d s i e n t i w n h e n C D 4 g r a d i e n t s w e r e
c o m p a r ed b et ween the t w so u b grou p s acc ord in g to c h a n g e s c o r e s o f:
1. L o C (t = 2 .1, d f = 3 0 , p = 0 4 . 9 0 ): I n c r e a sed s e n s e o f c o n t r o l o f o ’s n e o w n l i f e
(I n c r e a s e d c o n t r o l: 1 6 in d ivid u als w i t h a creas d e ed LoC s c o r e) an d Decreas ed s e n s e
of c on trol (D e c r e a s e d c o n t r o l: 1 4 i n d i v i d u a l s w i t h a n i n c r e a s e d L o C s c o s u r e b ) g r o u p s
[ T a b l e 1 an 3 d Fi gu re 3 7 ] ;
2. M C S (t = 2.4, d f = 3 0 , p = 0 2 . 7 0 ): Imp ro ved p s ych ol o gi cal fu n ction in g (Imp r o ved
Q o L : 1 6 in d ivi d u al s w i t h a n c r e i a s n ed M C S s c o r ) e a n d D e c r e a s e d ch p olo s y gi cal
f u n c t i o n i (D n g e c r e a s e d : Q 1 o 4 L i n d i v i d u a l s w i t h a d e c r e a ) s se ud b grou s c o r pe s [Ta b le 32 an d Fi gu re 3 8 ] ; a n d
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 12 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
3. P S Q I (t = 2.1, d f = 3 0 , p = 0 4 . 7 0 ): I m p r o v e d s l e e p q u a ( l 2 i 3 t in y d ivi du al s h a d a
d e c r e a s e P d S Q I s c o r ) e an d D e c r e a s e d s l e e p q u a l (7 i ind t y i v i d u a l s h a d a n i n c r e a s e d
s c o r e) s u b g r o u p s [ T a b l e 3 an 3 d Fi gu re 3 9 ] .
T able 31: Me a n ( 95% C.I .) C D 4 -c T e ll c ha nge ove r the f ive mont h ( c e lls per l per month) in HI Vinf
e ct e d in dividua ls of t he I n c r e a se d c o nt ro l a n d De cr e as e d c ont r ol subgroups
CD4 T-c e ll c ha nge ( ce lls pe r l pe r month)
I n c r e a se d co n t r ol D e c r ea s e d c o nt ro l
Me a n CD4 gr a die nt
+ 9
- 15
( 9 5 % C . I . )
(- 2.8 t o + 21.7) (- 34.7 t o - 5.2)
n 16 14
Mean (95% C.I.) CD4 gradient (cells/ul/month)
4 0
2 0
0
- 2 0
- 4 0
I n c r e a s e d c o n t r o l D e c r e a s e d c o n tr o l
Fi gur e 37: M ea n ( 9 5% C . I .) C D 4 gr a d i en ts ( c e l l per s l pe r mo nt h) in t he I n c r e a se d co n t r ol ( de cr e as e d
s c o r e s o f t h ) e and D L e o c C r e a s e c d on t r o l ( i n c r e a s s c o e r d e s o f t h ) e subgroups L o C
T able 32: Me a n ( 95% C.I .) C D 4 -c T e ll c ha nge ove r the f ive mont h ( c e lls per l p e r m o -n
t h ) i n H I
inf e ct e d in dividua ls of t he Im p r o v e d QoL a nd D e c r e a s e QoL d subgroups
CD4 T-c e l l c h a n g e ( c e l l s p e r l per month)
I m p r o v e d Q o L De c r ea s e d QoL
Me a n C D 4 gr a d i e nt + 11
- 19
( 9 5 % C . I . )
(- 1.4 t o 21.4) (- 40.5 t o + 2.5)
n 16 14
Mean (95% C.I.) CD4 gradient (cells/ul/month)
4 0
2 0
0
- 2 0
- 4 0
p = 0 . 0 4 9
p = 0 . 0 2 7
I m p r o v e d Q o L D e c r e a s e d Q o L
Fi gur e 38: M ea n ( 9 5% C . I .) C D 4 gr a d i en ts ( c e l l per s l pe r m o n t h ) i n It mpr h e ove d me nt a l ps yc hologic a l
f unct ion in g (Im p r o v e QoL: d i n c r e a s e d s c o r e of s the M C S ) and De c re a se d p s y c h o l o g i c a l f u n c t i o n i n g
(D e c r e a s e d : d Q e o c L r e a s e s d c o r e s of t he MCS ) subgroups
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 13 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
T able 33: Me a n ( 95% C.I .) C D 4 -c T e ll c ha nge ove r the f ive mont h ( c e lls per l p e r m o -n
t h ) i n H I
inf e ct e d in dividua ls of t he Im p r o v e d s l e e p q u a l and i t y D e c r e a s e d s l e e p q u a l subgroups i t y
CD4 T-c e ll c ha nge ( ce lls pe r l per month)
I mpr ov e d s l e e p q u a l i t De y c r ea s e d s l e e p q u a l i t y
Me a n C D 4 gr a d i e nt
+ 4
- 26
( 9 5 % C . I . )
(- 8.4 to + 1 8.2) (- 48.9 t o - 1.9)
n 23 7
Mean (95% C.I.) CD4 gradient (cells/ul/month)
6 0
4 0
2 0
0
- 2 0
- 4 0
- 6 0
I m p r o v e d s l e e p q u a l i D t e y c r e a s e d s l e e p q u a l i t y
Fi gur e 39: M e an (95% C.I .) CD 4 gr a d i en ts ( c e l l per s l pe r m o n t h ) i n It mpr h e ove d sl ee p quali ty
( d e c r e a s e d s c o r e s o f t h P e S Q I ) and D e c r e a s e d s l e e p q u a l ( i t i y n c r e a s c s o e r d e s of t he P S Q I ) subgroups
C o n c l u s i o n :
p = 0 . 0 4 7
T h e s e f i n d i n g s s u g g e s t t h a t t h e r a t e o f d e c l -c i e n l e l i n c o t -in u h fe e n cted t C D 4 o f T H I V
i n d i v i d u a l is s a s s o c i a with t e d c h a n g e s c o r s e i n t h pe ercei ved con tr ol , p s ych ol ogi cal fu n ction in g
a n d s l e e q p u a l i s t cales y r a t h e r t h a n a c t u a l s c o r es o n o n e o c c a , i s .e. i o th n os e wh o inc r e a s ed C D4
T-c e l l c o u n t o s v e r t h e fi v e m o n t h eriod p i m p r o e v d i n t s h c e o r es of L o C, M C S an d P S Q I .
Ra te of ch a n g e i n HI V vi ra l loa d ( HI V vira l loa d g r a d i e n t)
V i r a l l o a d l e v e l s a r e a n o t h e r m a j o r p a r t o f t h e r o u t i n e m o n i t o r t i n h g e o H f I -in V fec ted
p a t i e n t s, p art icu larl y wi th reg ard to d ru g t reatmen t. Altho u g h n o n e -in fe o cted f t h e H I V
i n d i v i d u a l s in t h i s s tu d y h a d t a k e n a n y a n t i-retr ovi ral treat men t , th e r ate o f ch an ge in viral l oad
l e v e l s -tran ( l o sg fo rmed fi gu res ) w as calc u lated b e t w e e n t h recru e it men t ti me p oi n t a n d fou r
m o n t h s l a t e r . S i m i l t a o r t h e r e s u lt s o f t -c h e l C D l 4 T b l o o d c o l l -e
c t i o n , n o t
i n d i v i d u a l s r e c r u i t e d h a d v i r a l l o a m d e l a e s v u e r l s e d r i d n u g t h e s t u d y p e r i o d Ap [ p e n d i x 6 : Tab le A-3 7 ]. Of t h e 6 3 p a r t i c i p a n t r s e c r u i , ot ne l y d 3 8 p a t i ) h ad e sn u ffi t ci en s t d ata ( fr om 6 0 wh . ich 3 %
t o c al c u l a t e t h e v i r a l l o -t a r d a n s l f o e r m v e l d ) grad ( l o ien g ts d u ri n g th e s tu d y p eriod . With in th e
a b o v e 3 8 p a t i e n t s , 3 2 p a r t i c i p a n 2 t 9 s ( m a l e s a n d t h females r e e ) co mp let ed th ei r q u es tion n aires .
T h e r e s u l t s o b t a i n e d f r o m 3 2 s u b j e c t s a n d es t h ue lts r fro m 2 9 mal e s u b ject s are s i m ilar an d th e y
h ave th e s ame t ren d , s o on l y th e r e s u l t s f r o m 2 9 m a l e s re u b pj res e c t en s ted a .
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 14 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
This viral l oad l evel g rad i en t ove r th e fi v e mon th s w a s in ves tig ated b y co rrelati on
an al ys es fo r as s oci at i on with the s c o r es o f t S h t e a t e a n x i e t c y o s r e , , I P S E S S, L o C, M C S a nd
P S Q I . Th ere was n o s i gn i fi can t co rrelati o n a t e i t h e r r e c r u i t m e n t or a f t e r f o u r m o n t h s t i m e p o i n t s
[Ap p e n d i x 6 : Tab l e A-3 8 ]. S i milar t o th e an al ys es of th e C D4 grad ien t , ch an ge s c o res of th e
s t r e s s p e r c e p t i o n s ( S t a t res e , Pa Sn S x i an e d t IES y s ) c an o d p erceived q u a l i -o t f y -life s cal es ( LoC ,
M C S a n d P S Q I) o v e r t h e s a m e p e r i o d w e r e c o r r e l a te d with th e viral l oad lev el g ra d ien t.
H o w e v e r , t h e v i r a l l o a d l e v e l g r a d i e n t we s r e n ot s i gn ifi can tl y as s ociated with th e c h an ge s cores
of a n y s e l f-r e p o r t v a r i a [Ap b l e p e n d i x 6 : Tab le A-3 9 ].
Co n c l u s i o n :
Viral load l e vel w as n ot s i gn ifican tl y as s ociated with an y of th e p ercei ved s t res s o r
q u a l i -o t f y -li fe m e a s u r es u s ed i n t h i s . s t u d y
R a t e o f c -c e h l l a c o n u n g t e ( N K g i r a n d i e n t N ) K
Becau s e N K -c e l l l e v e were l s s h own to b e a s s o c i a t d e with th e s tres s p ercep ti on in th e
u n ivers it y s tu d en ts [ 3 . 1 ], f o r e x p l o r a t o r y p u r s, p o th s e NK grad ien t was al s o calcu lated fro m th e
s a m e b l o o d s a m p l e d -c a t e a l l a s g t r h a e d C i D e 4 n T t s . O n e s - a m p l e d a t
c e l l lcu c a lation . Hen ce 37 s u b j e cts h a d s u f f i c i e n t d a t a gr f ad ien r o ts m w h i c h
d u rin g th e s tu d y p eri od . W i t h i n t h e a 7 b o p v a e t i 3 e n t 1 s p , a r t i 3 c i p a n t s 2 ( 9 m a l e s a n d t w o
females ) co mp let ed th ei r q u es tion n aires . T h e r e s u l t s o b t a i n e d f r o m 3 1 s u b j e c ts a n d t h e r ults e s
fro m 2 9 mal e s u b j ect s are s i milar an d th ey h a ve th e s a me t ren d , s o on l y th e res u lts fro m 2 9 male
s u b ject s were p res en t ed .
T h e N K g rad i en t ove r t h e fi ve mon th s an d th e s cores o f th e p s ych olo gical meas u re s were
fu rth er i n v e s t i g a t e d b y c o elation r r an al ys es for as s oci at i on s with the l e v e l s o f s t r h e s -related s
p ercep ti on s (S t a t e a n x i e t y s , PSS c o r e a n d I E S) an d the p e r c e i v q e u d a l i -o t f y -life an d s leep (L o C,
M C S an d P S Q I ). R es u lt s s h ow t h a t g t r a d h i e n t s o v N e K r f i v e m o n t we h s r e n o t s i g n i f i c a n tl y
a s s o c i a t with e d th e s cores of St at e an xiet y, I E S, PSS L o C, M C or S P S Q I a t e i t h e r recru it men t o r
a f t e r f o u r m o n t h s , e x c e p t w i t h t h e P S Q I a t r e c r u i t m e n t [Ap p e n d i x 6 : Tab le A-4 0 ]. Th ere was a
s ign ifican t cor rel at ion ( r = 0 .4 4 , p = 0 . 0 1 7 ) b e t w e e n t h e dN ien K t an g r d a th e P SQI s core at
recru it men t b u t th is correl at i on was n ot r ep licated at th e fou r m o n t h a s s e s s m e n t p o i n t Ap [ p en d ix 6 : T a b l -4 e 0 ]. Si A mi la r to th e an al ys es o f th e C D4 grad ien t, ch an ge s co res o f th e s t res s
p e r c e p t i o n s ( S t a t e a n x i a e n t d I y E S s ) c o a r n d e s q , -o u a f l -l P i S f t S e y s c a l e s Lo ( C , M C S an d
P S Q I) o v e r t h e s a m e p e r i o d w e r e c o r r e l a ted with NK grad ien ts . Howeve r, n on e of th es e
c o r r e l a t i o n s w e r e s t a t i s t i c a l l y s i g n i f i c a n t [Ap p e n d i x 6 : Tab le A-4 1 ].
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 15 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
C o n c l u s i o n :
Th e l e v e l s o f o r c h a n g e d l e v e l s o f N -c K e l l c o u n t were n ot s ign ifi can tl y as s ociated with
an y of th e s tres s p ercep ti on o r q u alit y o f l ife meas u res u s ed i n t h i s . s t u d y
S u m m a r y :
P a t i e n t s d i a g w n o i s i t hs ave h h igh H er I sV tres s p ercep ti on th an u n ivers it y s tu d en ts facin g
e x a m s , a n d t h e h i g h e r l e v e l s d id n ot ch an ge s ign ifican tl y o ver th e fou r m on th s of t h e s tu d y
p eriod . On t h e ot h er h an d , t h ere was little d ifferen ce in th e State an xiet y l evel s b e t w e e n t h e
H I V-in fect ed in d ivi d u al s a n d t h e u n i v e r s i t y s t u d e n t s f a c i n g a c a d e m i , c e a x a n m s d -in fected H I V
individual s wh o r e p o r t e d l ow l e v e l s o f s t r e s s a l s o r e p o r te d l o w e r State an xiet y s c or es t h a n
in d ivid u al s wh o r e p o r t e d h igh levels o f s t res s . Th e imp act o f b ein g d i a g n o s e d a -s
c a r r y i
in fection d ecreas ed o v e r t h e s t u d y p e r i o d . the A l i m t p h a o c u t g h l e v e d l e s c r e a se d , i n d i v i d u a l s
w i t h h i p g e h r c e i v e d s t r e con s s s is ten tl y s h owed h igh er s c o r es o f t h e i m p a c t t h a n t h e i n d i v i d u a l s
w h o r e p o r t e d l o w s t . r e s s
Th e p e r c e i v e d q u a -o l f -l i i t f e y (l ocu s of co n trol , p s ych ol ogical fu n ction in g an d s leep q u a l i ) t s y c a l e s d i d n o t c h a n g e s ig n i f i c a n o t v l e r y t h e s t u d y p e r i o d , a n d lo w e r s t r e -s
s e d H I V
in fected in d ivi d u al s con s tant l y r e p o r t e d ing h a v a h igh e r s en s e of taki n g con tr ol o f on e’s own
l i f e , b e t t e r p s y c h o l o g i c a l f u n c t i o n i n g a n d b th e e t h t i e g r h e r s l s t e r e p s s d q u a l i t y t h a n
in d ivid u al s .
No t a b l , y i t w a s c o n c l u d e d t h a t th e s c o r e s o f s t r e s s a p e n d r c e p e p t r c i e o i n q v u e a d l -o i t f -life y
s c a l e s at a s i n g l a e s s e s s m e n t p o i n t ( r e c r u i t m e n t o r f o u r m o n t h s l a t e r ) w e r e n o t a s s o c i a t e d w i
t h e r a t e o f c h a n g -in e fected i n p at ien t ts h (n e o t re c C e i D v 4 i n g a n c t i-re o u trovi n t ral s i n H I V
t r e a t m e n t ); b u t th a t t h e r a t e o f d -c e c l l l c o i u n t e o i f n -in fected H t I h V e in dC ivi D d4 u al s T w a s
a s s o c i a t e d w i t h c h a n g e s i p n e r t c h e i v e d q u -o a f l -l i t f y (L e o C , M C S a n d P S Q I s ) c o r e s.
Th es e res u lt s su p p o r t t h e c e n t r a l h y p o t h e t s i h t s a s tres s cau s es d et ri men tal effects u p on
w e l l -b e i n g; an d fu rt h er, t h a t a n i m p r o v e m e n t i n p e r c e i -o v f e -li d fe q mu a y l hi at v e y b e n e f i cial
e f f e c t u p o n d i s e a se p r g o r e s s n i , o i . e . p s y c h o l o g i c a l i m p r b o e v be en m efi e n ci t al f m o a r y h eal th .
Th is lead s on to t h e n e x t ves i ti gat n ion o f p s ych ol ogi cal in terven tion u p on t h e p s y c -n h e o u r o-
e n d o c r i n -im o mu n e n et work , p art icu larl y u p on th e p e r c e i v e d q u a -o l f -li i t fe y s cal es an d th e
d i s e a s e p r o g r e s s i o n m a r k T-c e r l , l c o C u D n t 4 [ 3 . 2 .
2 ]
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 16 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
3 . 2 . T 2 h e i n f l u e n c e o f ps y c h o l o g i c a l i n t e r v e n t ion u pon d i s e a s e pro g r e s i pa o n ra mete rs in H I V-i n f e c t e d i n s d e d i c v o n i t r d o l u l a e d l t s r i a ( l r o v a p e r n r i o d a ) o f m o u r m o n t h
Th is s t u d y i n ves t i gat es t h e h yp oth es is th a t ps yc h o l o g i c a l i n terv en tion can c o u n t e r a c t
d e t r i m e n t a l e f f e c t o f s t r e s s u p o r n o g d r s i e s i e a o s n, e i . e . d e c l i -cel n e l cou o nf ts , t h e C D 4 T
a c t i n g t h r o u g h t h e p r o p o s e d i n t e -n g e r u a r t o-e e n d d o p c s r y i c h n -i o
mmu n e n et wor k.
3 . 2 . 2 . Ef 1 f e c t o f p s y c h o l o g i c a l i n t e r v e -in n fe cted t i o n u p o n
i n d i v i d u a l s
Th e in fl u en ce of th e p s yc h o l o g i c a l i n t e r v e n t m i e o n t a l u w p o e l n l-b ei n g (p ercei ved s tres s
a n d q u a l -o i f t -life y ) w a s e a x m i n e d b y c o m p a r i n g t h e n t s h c e o r s e l -rep s f o rt q u es ti on n ai res
b e t w e e n t h e S e l -h f yp n os is , J oh rei grou p s an d t h e w a i t-l i s t e d on tr c ol grou p .
T h e S t a t e a n x i e t y s c e o s r o r th e P SS s core s d id n ot ch an ge s ign ifican tl y fr o m th e B as elin e
t o t h e P o s t-i n t er ven t i on t i me p oin t (f ou r mon th s after th e Bas elin e) in an y g rou p , an d th e s cores
d i d n o t d i f f e br etween gr ou p s at ei th er as s es s men t p o i n t [Ap p en d ix 6 : Tab le A-4 2 ]. T h e I m act p
Even t Scal e ( IES ) s co res i m p r o v e d s i g n i f tly i c ba et n ween th e p r e- a n d p o s t- i n t e r v e n time t i o n
p o i n t s (F = 1 4 .1, d f = 4 8 , p < 0 . 0 0 1 . ) Th ere w e r e, h o w e v e r , n o s i g n i f i c a n t g r o u es p in d i f f e r e n c
t h i s c h a n , g i.e. e n o s i gn ifi can t time x g r o u p in teraction ( F = 0 . 8, d f = 4 8 , n [T s ) a b l e 4]. 3
T able 34: Me a n ( 95% C.I .) l e v e l s o f t -i h n d e i v i d I u a E l S t s h e i S i n e l -h n f yp n t o s i h s , e J oh r e H i a I nd V wa i tl
i s t e d ontrol c groups a t t h e B a s e l i and n e P o st -i n t e r v e n t i o n t i m e p o i n t s
I E S
B a s e l i n e
P os t -i n t e r v e n t i o n
S e l f-hypnos i s J o h r e i C o n t r o l s S e l f-h y p n o s i s J o h r e i C o n t r o l s
Me a n s c o r e 23.1 23.5 28.4 16.0 20.1
21.2
( 9 5 % C . I . ) (19.2 - 27.0) (18.3 - 28.7) (24.2 - 32.6) (12.3 - 19.7) (15.2 - 25.0) (17.2 - 25.2)
N 21 12 18 21 12 18
Th e o c L u s o f C o n t r o l ( L o C (F ) = 1.1, d f , = n 4 s), 8 M e n t a l C o m p o n e n t s S -u
m m a r y o f S F
3 6 (MC S ) (F = 0.8, d f = , n 4 s) 8 o r P i t t s b u r g h S l e e p Q u a l i t y I n v e n t o r y ( P S (F Q I ) = 1.9, d f , = 4 8
n s ) s c o r e s d i d n ot ch an ge s i gn ifican tl y f r o m t h e B a s e l i n e t o t h e P o s t-in ter ven tion t ime p oin t in
a n y g r o u p , n o r d i d i t d if f e r b e t w e e n g r o u p s a t e i t h e r a s s e s s m e n t p o i n t, i.e. n o s ign ifican time x
g r ou p i n t e r a c s t [Ap i o n p en d ix 6 : T a b l -4 e 3 ]. Hen A ce, it was c on cl u d ed th at p s ych ol ogical
in terven ti on d id n ot affect s tres s p ercep tion or p erceived q u a l i -o t f y -life s i gn ifi can tl y.
Ho we v e r , a v i h n g s h own in th e p re vi ou s s ection th at th e w o r s i n i in n g th e l e v e l s o , f t h e L o
M C S a n d P S Q I o v e r t h e s t u d y w p e r e pi os o itivel d y as s oci at ed wi th th e d e c l i n e i n t h e -
C D 4 T
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 17 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
c e l l c o u n t [ 3 . 2 . 1 . 3 , ] th e d is tri b u ti on s of th e n u m b e r f o p e o p l e w h o w e r o e v i n m g p o r w o r s e n i n g
in th e level s of ( 1 ) L o [ Tab C le 3 5 ], (2 ) M C S [Tab le 36] an d (3 ) P SQI [Tab le 37] w e r e f u r t h e r
e x a m i n e u d s i n g t h e I n t -t e n o-t t r e i a o t n a n a l y s i s ( T h e p a r t i c i p a n t s w h o f a i l e d t o p r o v i d -rep e s e ort l f
q u e s t i o n n a i r e d a t a w e r e a d d e d i n t h e n u o m f b e t r D h s e c r e a s e d c o n t r o l, D e c r e a s e d o Q r o L
D e c r e a s e d s l e e p q u a l g i r o t u y p s ) f o r t h e e x p l o r a t o r y . p u r p o s e
T able 35: S u m m a r y o f ) t o h f e -i t n d i h n v e i u d u m a l H b s I w e V h o r s e s c h a n g in ( e s the % LoC be t we e n t he
B a s e l i n e a nd p os t-i n t e r v e n t i o n e i t h e r d e c r e a s e d I n ( c re a s e d c o nt r ol: i n c r e a s e d s e n s e o f one’s c o n t r o l i n
o w n l i ) f o e r i n c r e a s e d (D e c r e a s e c d o nt r ol) i t n h e S e l -hypnosis, f Johrei and wait-l i s t e d ontrol c groups
I n c r e a s ed c o n t r o l Decr ea s ed c o n t r o l T o t a l
Self-h y p n o s i s 1 0 / 2 1 ( 4 8 % ) 1 1 / 2 1 ( 5 2 % ) 2 1
J o h r e i 9 / 2 ( 1 7 5 % ) 3 / 1 2 ( 2 5 % ) 1 2
Co n t r o l 1 0 / 1 8 ( 5 5 % ) 8 / 1 8 ( 4 5 % ) 1 8
T o t a l 2 9 2 2 5 1
T able 36: S u m m a r y o f t h e n u m b e r s %) ( o f -i t n d i h v e i d u a l H s I w V h o s e c h a n g in e s the M CS be t we e n t he
B a s e l i n e a nd p os t-int er ve nt ion e it her in cr e as ed (Im p r o v e d : Q o i L m p r o v e d p s y g c i h c o a l o f u n c t i ) or o n i n g
d e c r e a s e d (De cr e as e d Q o L ) i t n h e S e l -h f yp n o s i s , J o hr e i a nd wa i t-l i s t e d ontrol c groups
I m p r o v e d Q o L D e c r e a s e d Q o L T o t a l
Self-h y p n o s i s 11 / 2 1 ( 5 2 % ) 10 / 2 1 ( 4 8 % ) 2 1
J o h r e i 7 / 1 2 ( 5 8 % ) 5 / 1 2 ( 4 2 % ) 1 2
C o n t r o l 7 / 1 8 ( 3 8 % ) 1 1 / 1 8 % ( 6 ) 2 1 8
T o t a l 2 5 2 6 5 1
T able 37: S u m m a r y o f t h e n u m b e r s %) ( o f -i t n d i h v e i d u a l H s I w V h o s e c h a n g in e s the P SQI bet we e n t he
B a s e l i n e a nd p os t-i n t e r v e n t i o n e i t h e r d e c r e a s e d I m ( p r o v e d s l e e p q u a ) l o i r t i y n c r e a s e d (De cr e ase d sl ee p
quality) i t n h e S e l -hypnosis, f J o hr e i a n d wa i t-l i s t e d ontrol c groups�
I m p r o v e d s l e e p q u a l i t D y e c r e a s e d s l e e p q u a l i T t o y t a l
Self-h y p n o s i s 15 / 2 1 ( 7 1 % )
6 / 2 1 ( 2 9 % ) 2 1
J o h r e i 9 / 1 2 ( 7 5 % )
3 / 1 2 ( 2 5 % ) 1 2
C o n t r o l 1 0 / 1 8 ( 5 5 % ) 8 / 1 8 ( 4 5 % ) 1 8
T o t a l 3 4 1 7 5 1
T h e p e r c e n t a s g e o f t -i h n e f e c H I t V e d i n d i v i d u a l . s M C w S h o r o P S Q i I m p r o v e d t
s c o r es i n t h e J o h r e i g r o u a p l l w h e i r g e h e r t h o a s n e i t n h t h w e a i t-l i s t e d on trol c gr ou p , a l t h o u g h
thes e d i f f e r e n t p e r c e n t a g e s b e t w e e n t h e t h r e e g r o u p s d i d n o t a c h i e v e s t a t i s t i c a l s i g n i f i
(Self-h y p n o s i s v s . w a i t-l i s t e d on tr c ol : c h i -s q u are = 0 . , 2 a n J d o h r e i v s . w a i t-l i s t e d o n t c r o l : c h i -
s q u are = 1 .2 f o r t ; h S e l f-h yp L o n o C s i s v s . w a i t-l i s t e d on tr c ol : c h i s q u a r = e 0 . 7, an d J oh rei vs .
w a i t -l i s t e d o n t c ro l : c h i -s q u a r e = 1 .1 f or t h e MC S; an d Self-h y p n o s i s . w v a i t -l i s t e d on trol c : c h i -
s q u a r e = 1 . , 1 a n J d o h r e i v s . w a i t-l i s t e d o n t c r o l : c h i -s q u a r e = 1 .2 f o r t h e P S Q ). I
S a m p l e s i z e c a l c u l a t i o n s h o w s t h a t , i or t 1 3 3 w , o s u l b j d e c ts n e p e r d g r 1 o 2 u 1 p in ord er
t o s t h a h t 7 o 5 %, w or 5 8 % i n t h e J o h r e i , i s g s r i o g u n p i f c a n t l y d iffe ren t to t h e %, 5 5 o in r 3 8 %
th e w a i t -listed c o n t r o l g r , o u r p e s p e c t .
i v e l y
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 18 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
C o n c l u s i o n :
Ne i t h e r S e l f-h yp n os i s n or J oh rei ap p eare d to alter an xiet y or p ercei ved s t res s level s in th e
H I V-in fect ed i n d i vi d u al s (n o t r e c e i v i n g a n t i-r e t r o v i r a l t r e a t m e n ts). Th e i mp act o f b ein g aware
of c a r r y i -i n f g e c t i H I o n V d e c r oe ver a s th e d e s tu d y p eri od , b u t n e i t h e r t h e i n t e r v e n t ion of th e
Self-h yp n os is n or J oh rei aff ected th e d ecr eas e o ver th at fou n d i n t h e w a i t-l i s t e d o n t c r o l g r . o u p
No n e o f th e LoC , MC S an d P SQI s c o r es c h a n g e d, a n t d h e J o h r e i a n d S e -h l f yp n os i s gr ou p d id n ot alter th es e s co res s ign ifi can tl y o v e r t h e s t u d y , p alth e r ou i gh o d th e J oh rei g r ou p s h owed th e
h igh es t p e r c e n t a g e s imp w h o r ov ed in their s c o r e s all i n t h e p e r c e i d v e q u a l -o i t f -l y i f e s c a l . e s
S a m p l e s e i calcu z lat ion s h owed th at th e n u mb ers in each gr ou p were to o few t o d e mon s trate
s tatis tical l y s i gn i fi can t ch an ges .
3 .2 .2 .2 E f f e c t o f p s y c h o l o g i D 4 c a T-c l e l i l n t e c r o v -in u e n fected n t s i o n i n u p H o I n V C
i n d i v i d u a l s
Th e in fl u en ce of p s ych ol ogi cal in terven ti on u p on th e c h a n g e i n t h -cell e co C uD n4 ts T
(C D 4 g r a d i e n t: t h e d i s e a s e p a r a m e t ) e w r a s e x a m i n e in d o rd er to tes t th e h yp ot h es is th at
p s ych ol ogi cal in terven ti on ma y cou n terac t the d e t r i m e n t a l e f f e c t o df is eas s t e r e s s u p o n
p r o g r e s s -i i n f o e c n t e d i n d n i v i d H u . a I l s V
C D4 grad i en t s were c on s t ru cted for 1 5 p articip an ts in the Self-h yp n o s i s , t e n i n t h e J o h r e i
a n d 1 3 in t h e w a i t-l i s t e d o n t c r o l gr ou p s . A mean d ecl in e o f 1 2 cells p er l p e r m o n t h - i n C D 4 T
c e l l c o u n t s w a s s h o w n i n t h e w a i t-lis ted con trol gr ou p . T h e Kr u s k a l -Wallis ran k t e s t sh owed a
t r e n d t o w a r d s d i f f e r e n c e a m o n g t h e t h r e e g r o u c p h s i -s ( q u are = 5 .5 , d f = 2 , Mon te C arlo
s i g n i f i c a n = c e 0 . 064 ) . h e se T d i f f e r e n t s a t m r o e n g d t h e t h r e e g r o u p e w s r e c o n f i r m b y e d
follo wi n g c h i -s q u a r e a n a l y s e . s Th e re was a s ign ifi can t d e c r e a s e i n t h e r a t e - o f d e c l i
cells in p art ici p an ts wh o were t r a i n e d i n a n d p r a c t i s mp i n g ar ed J o wi h r th e i n d ic vi o d u al s in th e
w a i t -l i s t e d o n t c r o l (c h i -s q u a r e = 3 . 9 , d f -tail = ed 1 , p = t w 0 . o 0 7) 4 a n d S e l f-h yp n os is (c h i -s q u are
= 4 . 5 , d f = -tailed 1 , p t w = o 0 . 0 3) gr ou p s . Th ere was , h owe ver, n o d iffe ren ce in C D4 grad ien t
b e t w e e n t h e S e l -h f yp n o s i s a n d w a i t-list e d o c n t r o l g r o u p (c s h i -s q u a r e = 0 . 1 , d f = ) 1 [Tab , n s le 38
a n d F i g u r 0]. e 4
T able 38: Me a n ( 95% C.I .) le ve ls of C D 4 gr ad ie nt s (c o u n t s pe r l p e r m o n ) t i h n H I -inf V e ct e d in dividua ls
i n t h e S e l -hypnosis, f J oh r e i and wa i t -l i s t e d ontrol c groups
CD4 gr a die nt (c o u n t s per l p e r m o n ) t h
S e l f-h y p n o s i s J o h r e i C o n t r o l s
Me a n c h a n g e - 9 + 1 7 - 1 2
( 9 5 % C . I . ) (-17 to -1) (+ 6 t o + 28) (- 20 t o - 3)
n 15 10 13
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 19 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
CD4 gradient (95% C.I.) cells/month
50
0
- 50
N =
1 5
Hypnosis
1 0
Johrei
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 20 - I m p e r i a l o C n o d l o n l e g e L
1 3
Control
Fi gur e 40: M e a n s ( 9 5 % C . I . ) C D 4 g r a d o i v e e n r t the s f i v e m o n t h st s udy p e r i o from d the Base line t o t he
P os t -i n t e r v e n t i m o e n p o i nt
Th is fin d in g w a s f u r t h e r i n v e s t i g a t e d b y -to-t t h r e a t I a n n t a e l n y t s c i o s m o n p ari n g
p ercen tages o f in d ivi d u al s b etween th e two grou p s (d ecreas e or m a i n t a i ne d t h e -cell C D 4 T
c o u n t s ). Al l t h e d at a fr o m t h e s u b jects wh o with d rew wer e ad d ed in to th e n u mb er in th e grou p
i n w h i c h t h e s u b j e c ts d e c r e a s e d t -cells h e i [T r ab le C 3 D 9 ]. 4 T
T a b l e 39: P er c enta ge s ( numbe rs ) o f p a r t i c i p a n t -c s e ll cw oh unt o s ma e int C aD ine 4 d or T de c re a se d
ove r t he f ive mont hs in t h e S e l f-h yp n o s i s a nd J o h r e i and wa i t-l i s t e d ontrol c groups f o r t he
I n t e n t -t i o o-t n r e at a na lys is ( mis s ing da t a we r e a d d e d i n t o t h e n u m t b e h r e D i e n c r e a g s r e o d u ) p
G r o u p Ma i n t a i d n e C D 4 -cells T D e c r e a s e d C D 4 -cells T T o t a l
Self-h y p n o s i s 2 9 % (6 /2 1 ) 7 1 % (1 5 /2 1 ) 2 1
J o h r e i 5 8 % ( 7 /1 2 ) 4 2 % (5 /1 2 ) 1 2
C o n t r o l s
3 3 % ( 6 /1 8 ) 6 7 % ( 2/1 1 8 ) 1 8
T o t a l 1 9 3 2 5 1
T h e p e r c e n t -i a n g f e e c t e d o i f n d i v l t i d s u h a e w h o H I m V a i n t a i n -cell e d c o ut n th s e in C D 4 T
t h e J o h r e i ( g 5 r 8 o % u ) p w a s h i g h e r t h a n t h a t o f w a i t-l i s t e d on trol c g rou p (3 3 % ), b u t th e d ifferen t
p ercen t ages b et ween t h e t h ree g rou p s d id n ot ach ieve s tati s tical s ign ifican ce. Th e s amp le s ize
c a l c u l a t i o n s h a o t w i t s w o t u l h d n e e d 8 4 s u b j e c ts p e r g r o u p t o tha s t 5 h 8 % o w in th e J oh rei g rou p
i s s i g n i f i c a n tl y d iffer en t to t h e % 3 3 i n t h w e a i t-listed c o n t r o l g . r o u p
C o n c l u s i o n :
p = 0 . 3
0 3
N o t s i g n i f i c a n t
p = 0 . 7 0 4
As s h own in th e p revi ou s an al ys is [ 3 . 2 . 1 ], C D -c 4 e T l l c o -in u n fected t s in d ivi i dn u al s H I V
w h o w er e n o t r e c e i v i n g a n t i-r e t r o v i r a l t r e a t m e n t i n t d h e c w r a e i t-l a s i e s d t e d on tr c o l gr ou p .
H o w e v e r , t h i s d e c r e a s -c i ell n cou g n t ap r pe eared n d to o bf e reve C rs D ed 4 b y T th e train in g an d
p r a c t i c e o f J o h r e i, a l t h o u g h t h i s w a s n o t s u p p o r t e d -t o-t b y reat t an h e al ys i in s , t wh e n it le i to hn e
����

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
t r a i n i n g a n d p r a c t i c e o f S -h e l yp f n os is d id n ot ap p ear to affe ct th is tren d . S a m p le s i ze calcu lation
s h o w e d t h at t h e n u mb ers of each g rou p w ere to o few t o d em on s t rate s tati s ticall y s i gn i fican t
ch an ges .
3 .2 .2 .3 E f f e c t o f p s y c h o l l o in g i ter c a ven ti on u p on o t h e r i m m u n o l o g i c a l m a -r
k e r s ( l o g
tran s for med v i r a l l o a d l e v e ls a n d -c e l l N c K o u n t s )
i n -i n f H e I c t e V d i n d i v i d u a l s
V i r a l l o a d l e -t v r e a l n s f o ( r l m o e d g ) g r a d i e n t s w e r e c o n s t r u c t e d f o r 1 4 p a r t i c i p a n t s i n - S e l f
h y p n o s i s , 1 2 i n J o h r e i a e n w d a i t-l 1 2 i s i t n e d o t n t c h r o l g r o u p s NK ; a gn rad d ien ts were
c o n s t r u c t e d f o r 1 5 p a r t i c i p a n t s i n S -h e y l p f n o s i s , 1 0 i n J o h r e i g r o u p s a n d 1 2 i n th e w a i t-listed
con trol s . T h e v i r a l l o a d l -t e r v e a n l s f ( o r l m o e g d ) d i d n o t c s h a i n g n e i f i c oa ver n t tl hy e fi ve
m o n t h s n o r K g d r a i d i d e n t , s a N n d t h e r e w e nr o e s i g n i f i c a n t d i f f e r e n c be etween th e th ree g rou p s
[Ap p en d ix 6 : T a b l es -4 A 4 a n d -4 5 , A r e s p e c t ]. i v e l y
C o n c l u s i o n :
As s h own in th e p revi ou s an al ys is [3 . 2 . ], 1 n e i t h e r v i r a l l o a d l e v e l n o r N -cell K c ou n t
c h a n g e d s i g n i f i c a n i t l n y -i n f e H c I t e d V i n d i v i d u a l s w h o w e r e n o t r e c e i v i n g a n t i-retr ovir al
t r e a t m e n t , a n d t h e t r a i n i n g a n d p r a c t i c e o f J o h r e i o -h r yp S e nl os f is d id n ot affect th e viral load
l e v e l o r t h e -g r a N d K i e n t .
S u m m a r y :
A l t h o u g h t h e r e s u l t s s h o w e d a p o s s i b i l i t y t h va e t h elp J o h ed r e ti o imp m a ry ove h a
p e r c e i v e d q u a -o l f -life i t y s c o r es , ne i t h e r S e l f-h yp n os is n or J oh rei ap p eared to alte r t h e levels o f
s tres s p ercep ti on or p er cei ved q u a l i -o t f y -l i f s e i g n i f i c a n t i l n y t -i n h f e c t e d H i I n d V i v i d u . a l s
T h e maj o r d i s e a s e p r o g r I e V-in s fect s i on o , C n D 4 m -c T a e l r l k c o e u n r , t was s o s hf own tH o
d e c r e a s e o v e r t h e s t u d y in p th e r w i a o i d t -l i s t e d o n t c r o l g r o a u s p e x p e c . t Th e d t rai n in g an d
p r a c t i c e o f S e l -h f y p n o s i s d ni ot d ap p ear t o af fect th is d e c r e a s e. In c o n t r a s t , th is d ecreas in g tren d
ap p eared to b e re vers ed s i g n i f i c a b n y t l t h y e in t r in a g an d p ract ice of J oh rei in th os e in d ivid u als
w h o c o m p l e t e d t h e . Si s gn t ifi u d can y ce w as los t in t h e i n te n t i o -t n o-t r e a t a n a l y s , i bs u t th is was
s u gges t ed t o b e rel at ed t o t h e small s amp l e s ize. Hen ce, th i s cou n teractin g ef f e c t o f J o h r e i on
d ecreas i n g t ren d was fu rt h er in ves ti gated in th e n ext s tu d y [3 .2 .3 ] e xamin in g th e ra te of ch an ge
i n C D -cell 4 T cou n ts in t h e 1 2 m o n t h s p e r i o b d o s t h p r i o r t o ( i n o r d e xa r mi t no e b as el in e
d i f f e r e n c e ) an d aft e r p art ici p an ts s t a r t ing e i t h e r o f t h e i r t r a i n (in i n g ord s er t o e xami n e th e effect
o f t h e i n t e r v t e r n a t i n i o n ).
g s
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 21 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Th es e res u l t s p r o v i d e s u p p ort fo r the h yp oth es is th at learn in g an d p racti s in g p s ych olo gical
i n t e r v e n t i o n , w h i c h p r o v i d e s a l t e r n a t i v e p e r s p e c t i v , e s a n o d f c o p i n g s k i l f o l r, s s tr es s fu l li fe
e v e n t s, i m p r o v e s p s yc h o l o g i c a l a n d p h ys i c a l w e l l-b e i n g.
3 . 2 . T 3 h e i n f l u e n c e o f p s y c h o l o g i c a l i C n D t 4 e -cells r v T e (d n t i i s e o a n s e pr u og p o res n s ion ma r ker) i n -i H n I f e c V t e d i n d i v i d u a l s ( c a s e c o n t r o l l e d s t u d y o v e r 2 4 m o n t h s p e r i o d )
T h i s s t u a d i y m e d t o r e p l i c a t e a n d e x p a l b o r v e f t i n h d e i n g [ s 3 . 2 . 2 . 4 b] y in cre as in g th e
s amp le s ize an d e x t e n d i n g t h e i n v e s t i g a t i o n p e r i o d f r o a tm otal f of i v 2e 4 mon m o n th t s h s t o
( C D 4 g r a d i e n t s w e r e c a l c u l a t e d o v e r 1 2 m o n t h s p r i o r gic t al o a n d a f t e r t h e p s y c h o l
interven t i on s com men ced ).
M a t c h e d a n ymis o n ed p at ien ts fro m th e d at ab as e [s ee Meth od s s ection 2 .1 .3 ] we re u s ed as
con trol s f or th is s tu d y. C o m p a r a b i l i w t a y s c o n f i r m e d b y c -cell o m cp oa u nr ts i and n g C D4 C D 4 T
grad ien s of th e c o n t r o l s w i t h t h e s t u d y llows g r o [3 u p .2 s .3 .1 a s ]. f o
3 . 2 . 3 . A 1 n a l y s i s o f b a s e l i n e d i f f e r e n c e s b e -c t e l w l e c o e u n t t h e t h r e e g
Th e r e w e r e n o d i f f e r ab e sn olu c e ts e Ci D4 n T-cell c ou n ts b etween th e th ree grou p s at th e
time p o i n t t h e i n t e r v e n t i o n s c o ( m F m e = n c , e 0 d . d f 7 = , 9 4 s; n Self-h y p n o s i s v s . D a t a -b
a s e
con trol : t = 0 . 6 , d , f n = s; J 7 o 4 h r e i v s . D a -c t a on b a trol s e : t = 0 . 9 , d , f n = s) [T 6 a 6 b l e 4 0].
T able 40: Me a n ( 95% C.I .) le ve ls of C D 4 -ce T l l (c o u n t s pe r l) i n H I -inf V e ct e d in dividua ls in t he gr ou ps o f t h e S e l -hypnosis, f J oh r e i a nd D a t a b a s e-c ont r ols a t t h T e r a i n i n g p e r i o d
CD4 T-c e lls ( c ounts per l )
S e l f-h y p n o s i s J o h r e i C o n t r o l s
Me a n 397
346
375
( 9 5 % C . I . ) (330 - 464) (278 - 414) (346- 404)
n 27 19 49
F u r t h e r, th e r e e r e n o w statistical d i f f e r e n s c e in C D4 grad ien ts b et ween th e th ree gr ou p s a t
th e P r e-i n t e r v tion e n p eri od ( F = , 0 d. f 2 = 9 3 , n s ; Self-h y p n o s i s v s . d a t a b on a s trol e c : t = 0 , . d 5 f =
7 5 , n ; s J oh rei vs . d a t a b a s e on c trol : t = 0 , . 2 d f = 6 7 , ); n a s n d th e a v e r a g e C D 4 g r a d i e n t o f r all 9 6
H I V-i n f e c t e d i n d i v i d u a l as w s a d ecl in e of seven cells p er l p e r m o [T n t a b h l e 1].
4
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 22 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
T able 41: Me a n ( 95% C.I .) C D 4 gr a die nt s i n -individuals H I V in the S e l f-hypnosis, Johrei and Dat a ba s e
control g r o u p s, a n d i n a l l the 9 6 i n d i v i d u a l s ( A L L ) a -i t n t h e r v P e r n e t i o n p e r i o d
CD4 gr a die nt ( c e lls pe r l p e r m o n t h )
A L L Se l f-h y p n o s i s J o h r e i C o n t r o l s
Me a n - 7 - 7 - 9 - 5
( 9 5 % C . I . ) (- 11 t - o 3 ) (-10 to -3 ) (- 14 t o - 4 ) (- 8 t o - 3 )
n 95 27 19 49
C o n c l u s i o n :
Th e r e w e r ne o s tati s ti cal d iffe ren ces in ab s olu te C D4 T-cell c ou n ts at Mon th 0 an d C D4
grad ien ts d u r i n g t h e P -i r e n t e r v e n t i o n b p e t r i w o e d e n t h e t h r e e g r o . u p s
3 . 2 . 3 . A 2 n a l y s i s o f t h e r a t -c e e o l f l c h c D4 a o n u g r n a e d t i e n i t ) n ( C C D 4 T
T h e o b j e c t i v e o f t h i s s t u d y w a s :
T o e x p l o r e t h e i n f l u e n c e o t f h p e s y c h o l o g i c a l i n t e r v e n t i o n , of p J a o r h r t e i , c u l a r l y
u p o n t h e r a t e c l o i f n e d b y c o m p a t r h i e n g C grad D 4 ien ts in each gr ou p b et ween the
p eriod s ove r th e 1 2 mon th s p r i o r t o -i ( nP terven r e ti on ) an d a f t e r th e in t e r v e n t s i o n
c o m m e n c e d ( P o s t-i n t er ven t i on ).
Th e C D 4 g r a d i e n t s f r o m a l l s u b j e c t u s l a w t e r d e s a c d a e l s c c r i b e d i n t d h e s ection m e t h o
[ 2 . 1 . 3 ] . T w o i n d i v i d u a l e x a m p l e s o f C D 4 g r a d i e n t r e g r e s s i o n in l es are p res en ted in Fi gu res 4 1
a n d 4 2.
Fi gu re 41 s h ows t h e C D4 grad ien t of on e d atab as e con trol p atien t as an e xamp le of th e
n a t u r a l c o u r s e -c e l o l f c o u n t ts h e i C n -i D n 4 f e c H t e T I d in V d i v i d u a l s . Fo r t h i s p a t i e n t , th ere is an
a v e r a g e d e c l i n e o f six (cells p er l p er m o n t h) in th e P r e-i n t e r v e n t i o n p e r f i o o u d r (cells a n d p er
l p er m o n t h) i n t h e P o s t -i n t erv en tion p eriod . T h e S e l f-h yp n os is p articip an ts ga ve s imilar
p rofiles t o t h os e s h own f or t h e d atab as e c on trol p atien ts , s o th at an in d ivid u al exa mp le of th ei r
C D4 grad i en t reg res s i on l i n es is n ot p res e n ted h ere.
I n c o n t r i gu a s re t 4 , 2 s h F o w s th e C D4 gra d ien t of on e J oh rei p articip an t. Th ere is a d eclin e
of 1 0 (cells p er l p e r m ) o n i n t th h e P r -i e n terven ti on p eri od , an d an in creas e of s e v en (cells p er
l p e r m ) o n i n t h e P o s t-i n t e r v e n t i o n .
p e r i o d
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 2 3 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
P r e -i n t e r v e n t i o n
M o n t h s (P r e (-) an d P o s t ( + ) f ro m t h e T r a i ) n i n g
P o s t -i n t e r v e n t i o n
M e a n d e c l i n e o f 6 c e l l pe s r l pe r m o n t h M e a n d e c l i n e c o e f l l pe s 4 r l pe r m o n t h
F i g u r e 41: CD4 g r a d i e n t s o f one c o nt r o l s u bj ec t a t t h e P r e-int er ve nt ion and P o st -i n t e r v e n t i o n p e r i o d s
P r e -i n t e r v e n t i o n
Training
Training
M o n t h s (P r e (-) a nd P o s t ( + ) f r t h o T e r m a i n i ) n g
P o s t -i n t e r v e n t i o n
M e a n d e c l i n e o f 1 0 c e l l pe s r l pe r m o n t h M e a n i n c r e a s e o f 7 c e l l pe s r l pe r m o n t h
Fi gur e 42: CD4 g r a d i e n t s o f one J o hr e i su b j ec t a t t h e P r e-int er ve nt ion a n d P o st-i n t e r v e n t i o n p e r i o d s
T h e d i f f e r e n t s t in r C e D n d 4 g r a d i e n ts b e t w e e n P - r a e n d P o s t- in terven ti on p eri od s was
e x a m i n e d b y A N O V A r e -m p e e a t s u e r d e a n a l ys e s f o l lowed b y u s in g th e 1 0 % trim min g m eth od
[ W i l c o x , 1 9 9 7 ] as d es cri b ed in th e Met h od s s ection [2 .5 ]. Th is s u b s equ en t ANOV A in clu d ed 7 8
s u b j e c t s ( 2 0 i n t h e S -h e l y f p n o s i s , 1 4 i n t h e J o h r e i a n d 4 4 i n d i v a s i e-con d u a l tr s ol s ). i n t h e D a t a b
Fi gu re 43 s h o w s t h e i n d i v i d u a l s c in h a t n h g e C D 4 g r a d i e n t s b t e h t e P w r e - e
a n d P o s t-
i n t e r v e n t i o n p e r elf-h i o d yp s n o i s i s n , J o t h r h e i g rou S p s an d D a t a b a s e-c on trol gr ou p s .
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 24 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
3 0
2 0
1 0
0
- 1 0
- 2 0
- 3 0
S e l f-hypnosis group ( n = 2 0 ) J o h r e i up g r (n o =14) D a t a b a s e-controls ( n = 4 4 )
F i g u r e 43: I nd ividua l c ha nge s i n CD4 gr ad i e nt s ( c e l l c o un ts per l per month) in t h e S e l f-hypnosis, J o hr e i
and D a t a b a s e-c o n t r o l g r o u p b s e t w e e n t h e P r -i e n t e r v e n t i a n o d n P os t -i n t e r v e n t i o n p e r i o d s
Th ere was a s i gn ifi can t d ecreas e in th e C D4 grad ien ts fro m t h e P r -i e n t e r v e n t i o n to p e r i o d
th e P o s t -i n t e r v e n t i o n p ( e r F i 9 o = . d 4, 1 d f = 7 5 , p < 0 . 0 0 1 ). Th e gr eates t imp r ove me n t in th e
C D 4 g r a d i e n ts w a s s e e n i n t h e J o h a r m e o i n g g t r h o e u p t h r e e g r o ( u p F s = , 2 d. f 4 = 7 5 , p = 0 . 0 9 5 . )
H a v i n g t h i res s u lt, fu rt h er e x p l o r a t i an v e al ys es were p er fo rmed as foll ows . T a b l e 2 4
s h o w s t h e s u m rm y a o f th e in creas in g an d d ecreas in g tren d s in C D 4 g r a d i e n t with s th e
a s s u m p t i t o h n a t a c h a n g e o f fou r or les s i n C D4 g r a d i e n t w a s d e f i n e d a s s t a y i n g s in t ce h e s a m e
f o u r C -cells D 4 ch T an ge p er l p e r m o was n t h wi th in th e 9 5% C .I. o f th e me an in 9 5 p atien ts in
t h e P r -i e n t e r v e n t i o n . p Acc e r i ord o d in gl y, in d ivi d u al s in th e I m p r o v i n s g u bgrou p imp ro ved th e
rate o f d ecl in e m ore th an fou r cells p er l p e r m o n t h i n C D 4 g r a d i e n t b - e t a w n d e e P n o s P t- r e
inter v e n t i o n p e r i o d s , i n d i v i d u a l W s o r i s n e n t i h s n e u g bgrou p i n c r e a s ed t h e r a t e o f d e c r b e y a s e
m o r e t h a n f o u r C D 4 -cells T p er l p er m on th , an d th e res t were in th e S t a ying-the-s a m e
s u bg r o u p.
Gr adient c hanges in Hypnos is
P r e Post
3 0
2 0
1 0
0
- 1 0
- 2 0
- 3 0
Gradient changes in Johrei
P r e Post
Gradient changes in Control
T able 42: P e r c e n t -indivi a g e d s u a l s i o n f t h e S H e -hypnosis, I l f V Joh r ei a n d D a t a b -c a s o e nt r o l groups whose
c h a n g e s i n C D 4 g r a d i e n t s b e t w e e n -i t n h t e r ve P n r t e i o n a n d P o st-int e r ve nt io n per io ds we r e e it her i n c r e a s e d , s t a y e d t h e s a m e w o i r t h d e a c r j u e d a g s e m d e n t t h a t a o f c h f a o n u g r e o f l e c s e s l l pe s r l pe r
month w a s d e f i n e d a t s h e s a m change e (S t a y i -the-s n g a m e subgroup), m o r e t h a n f o u r i n c r e a s (I e mpro v in g
subgroup), and m o r e t h a n f o u r d e c r e a s (W e o r s e n i n subgroup) g
G r o u p I m p r o v i n ( g % ) S t a yi n g-t h e-s a m e ( % ) W ors e ni ng ( % ) Total
S e l f-h y p n o s i s 9 / 20 ( 4 5 % ) 7 / 20 ( 3 5 % ) 4 / 20 ( 2 0 % ) 20
J o h r e i 11 / 14 (79 %) 2 / 14 ( 1 4 % ) 1 / 14 ( 7 % ) 14
Da t a b a s e-control 11 / 44 (25%) 21 / 44 (48%) 12 / 44 (27%) 44
Tot a l 31 30 17 78
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 25 - I m p e r i a l o C n o d l o n l e g e L
3 0
2 0
1 0
0
- 1 0
- 2 0
- 3 0
P r e Post

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
T h i s 1 1 / 1 4 ( %) 7 9 o f t h I e m p r o v i sn ub g grou p in th e J oh rei gr ou p i s s i g n i f i c a n tl y d ifferen t
to t h e 1 1 / 4 4 %) ( 2 i 5 n t h e t D a a b a s e-c o n t r o l g r o u p (P e a r s o n ' s c h i-s q u a r e = 1 2 . , d9 f = 1 , p <
0 . 0 01) w h i l e t h e 9 / 2 0 ( 4 5 % ) i n t h e -h S e yp l f n os is grou p was n ot s i gn ifican tl y d iff er en t to that in
th e D a t a b a s e-c o n t r o l g r (P o u e a p r s o n ' s c h i -s q u are = 2 .6, d f = 1 , n s).
Ha vin g s h own t h e s e f i n d gs i n u s i n g t r i m m e d s et, d a t f u a r t h e r an a l y s es u s i n g a l l o f t h e 9 6
s u b j e c t s w e r e p e r f o r m e d i n o r d e r t o c o n f i r m t h e r e s u l t s t h a t J - o h r e i m a y
c e l l c o u n . t s T h e a n a l y s e incl s u d e c o m p a r i s o n s b : e t w e e n
1 . T h r e e g r o u p s a t t h e P o s t-i n t e r v e n t i o n r i p o e d ( b y u s i n g t h e Kr u s k a l-W a l l i s r a n k t e s t ; s )
2 . P r e- a n d P o s t-i n t e r v e n t i o n p e r i o d s i n t h e -c D o n a t a r b o a l s e g r (b o y u p u s in g th e
W i l c o x o n S i g n e d R a n k t e s t s ) ; a n d
3 . P r e- a n d P o s t- i n t e r v e n t i o n p e r i o n d s t h e S e l -h f y p n o s i s a n d J o h r e i g r o u (b p y s u s in g
t h i l e c o x o n S W i g n e d R a n k t e s t [Tab s ) le 43 a n d F i g u r 4]. e
T a b l e 43: Me a n ( 95% C.I .) C D 4 gr a die nt s i n -individuals H I V in the Se l f-h y p n o s i s , J o h r e i a n d D a -t
a b a s e
control g r o u p s at t h e P r -i e n t er ve n t i o n an d P ost-i n t e r v e n t i o n p e r i o d s
CD4 gr a die nt ( c e lls pe r l p e r m o n t h )
P r e-i n t e r v e n t i o n
P o s t -i n t e r v e n t i o n
S e l f-h y p n o s i s J o h r e i C o n t r o l s S e l f-h y p n o s i s J o h r e i C o n t r o l s
Me a n - 7 - 9 - 5 - 1 + 3 - 2
( 9 5 % C . I . ) (-10 to -3 ) (- 14 t o - 4 ) (- 8 t o - 3 ) (- 4 t o + 3 ) (- 2 t o + 7 ) (- 5 t o + 1 )
N 27 19 49 27 19 49
Mean (95% C.I.) CD4 gradients (cells/mcl/month)
3 0
2 0
1 0
0
- 1 0
- 2 0
- 3 0
N o t s i g n i f i c a n t
p = 0 . 0 4 0
N o t s i g n i f i c a n t
N o t s i g n i f i c a n t
N o t s i g n i f i c a n t
S e l f - h y p n o s i s J o h r e i D at abase
c o n t r o l
Pre
P o s t
Fi gur e 44: Me a ns ( 95% C.I .) CD4 gr a die nt s ( c oun t pe r l per month)
in the S e l f-hypnosis a n d J ohr e i an d D a t a b a s e-control gr ou ps i n t h e P r e- and Post- i n t e r v e n t i o n p e r i o d s
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 26 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Th e C D4 grad ien ts of th e i n d i v i d u a l s i n t h e D -c a t o a n b t a r s e o l g r s ho owed u p a d ecl in in g
t r e n d i n b o t h t -i h n e t e P r v r e n t i o n a n d t h e P o s t-i n terven tion p eri od s (z = -1 . 5, d f = 4 8 , n s ). In
c o n t r a s t , t h e d e c l i a n t i n t g h e t -i r P n r e t e n d e r v e n t i o n p w e r a i s o d h a l an t d e d revers ed in th e J oh rei
grou p at the P o s t-i n t e r v e n t i p e o r n i (z o d = - 2 .1, d f = 1 8 , two-t a i l p e d = 0 . 0), 0 4 w h i p l a e t i e n t s in t h e S e l f-hyp n os is gr o u p c o n t i n u e d t o s h o w a d e c l i n i n g t r e z n d = - ( 1 . 1, d f = 2 6 , ). Su n s rp ri s in gl y,
h owever , th ere w as n o statisticall y s i g n i f i c a n t d i f f e r e n c e s yc b h e o t l o w g e i c e a n l t h e p
i n t e r v e n a t a b i a s o e-c n o n s t r o l i n a C n D d 4 g r a D d i e n t s a t t h e 1 2 m o n t h o f t h e P o s -in t terven ti on
p e r i o d ( S e l f-h y p n o s i s v s . D a t a -c b on a s tr e ol : t = 0 , . 2 d f = 7 5 , n s ; J o h r e i v s -con . D tr a ol t : a t b = a s e
1 . 0, d f = 6 7 , n s ).
S u m m a r y :
Th e r e s u l t s s u p p o r t t h e p reviou s fin d in gs th at th ere is a s t ead y d eclin e in p erip h eral b lood
C D 4 -c T e l l c o -in u n fe cted t s in d ivi i dn u al s (n H o I t r V e c e i v i n g a n t i-r e t r o v i r a l t r e a t m e n t); a n that d
the d e c l i n e o f C -c D e 4 l l T c o u n t a s p p e a r e d t o db ecreas e ed o r al le vi at ed b y th e trai n in g an d
p r ac t i c e o f J o h r e i t b, y Self-h b u t yp n o n os is . Hen ce, it was s u g ges ted th at l e a r n i n g a n d p r a c t i s i n g
J oh rei ma y h ave i m p r o v ed d i s e a s e p r o g r e s i s i n o -i n n f H e I c t e V d i n d i v i d u .
a l s
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 27 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
3 . 3 In v it ro i n v e s t i g a t i o n i n t o t h e p e o f s u f r e c t t str o
e f ss e h x o r m o n e s u p o n
N a t u r a l K i l l e r c e l l s
B a c k g r o u n d
N K -cel l s are i mp o rt an t cel l u lar c omp on e n ts of th e i n n a t e immu n e s ys te m in d efen ce
again s t i n fect i on an d m a l i g n a n cy, an d th ey are kn own t o b e a ffected b y s tr es s as s h own in
p r e v i o u s s t u d y .2 ] [ an 3 d . i1 n th e li terat u re [ S e g e r s t r o m & M i l l e r , 2 0 0 . 4 ] Ph armaco logi cal level s
of e x o g e n o u s g l u c o c o r t i c o i d are s kn own t o s u p p res s in fl ammation i n v i an v o d to s u p p res s NK
c ytot oxi c act ivi t y i n v i [ t Z r h o u e t a l . , 1 9 9 . 7 ]
In th is s eri es of in vi tr o e x p e r i m e n t s , t h e e f f e c t s o f e x p o s u r e t o t h e m s a hj or o r mon s t e, r e s
c o r t i s o l , a n d o t h -S e an r d mel s at on t ir n ), e p art s is cu larl h y with o r in m po h ys n iol e ogi s cal ( D H E A
l e v e l s -cells , w ere o n e xa mi N K n ed .
A i m s
A. T o c o n f i r m th e s u p p res s ive effect of a ma jor s tres s h o rm on e, c o r t i s o l , u p o n N K
c y t o t o x i c C A ), a an c d t to i e xp v lor i e t th e y u n d erl ( yin N K g mech an is ms at th e cel lu l ar
level.
B. T o e x a m i n e t h e r e l a t i o n s h i oth p s er en b e dt ogen w e e ou n s s tres s as s ociated h o rm on e s ,
D H E A -S an d mel at on i n , u p on NKC A.
W o r k i n g h y p o t h e s i s
“A n in vi tr o m od el of s u s t a i n e s t d r e s s i m p a i rs N K c y t o t o x c i t c i a v i .” t y
In vitr o mod el o f s u s t a i n e s t d r e s s is d efi ned as “m o r e t h a n 2 4 r s h o u o f e x re p o ts o u p p er
p h ys i o l o g i c a l l e v e l s o f c o r t i s o l”.
3 . 3 . 1
D e v e l o p m e n t a n d o p t i m i s a t i o n o f a f l o w c m y t e o t m h e o t f d r o i r c m e a s u r i n g N K C A
3 .3 .1 . 1 N K C A a f t e r C s i f o r n 2 4 c h o u r b s a t i o n o f P B M
T o i n v e s t i g a t e t h e -cells e , Pf BMC f e s we c t re cu lt o u red f fo r c 2 4 o hr ou t rs i s o l u p o n
with cort i s ol . Th ere for e t h i s exp eri men t was d es ign ed to d etermin e i f in cu b ation it s elf of
p e r i p h e r a l b l o o d m o n o n u c l e a r c e l ( l s P B M C s ) h a d K a n c y t o e t o f x i f c e a c ( t N i K v C i A u t ).
p y o n N
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 28 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Th e flow c yt omet r y met h od was u s ed . P BMC s f ro m 1 2 h ealth y s u b ject s were in cu b ated for 2 4
h ou rs p ri or t o as s es s i n g t h e N KC A.
Fi gu re 4 5 a an d Fi gu re 4 5 b s h o w m e a n ( 9 5 % C . I i n . d ) i v i d a u n a d l level s of N KC A p re an d
p o s t in cu b at i on for 2 4 h ou rs . N KC A l e v e l s w e r e i n c r e a s e d i n s i x i n d i v i d u a ls, d ecre as ed in th ree
an d s ta yed th e s ame in th ree. T h e r e p e a t e d m e a s u ANOV r e A s h owed a t r e n d t o w a r d s i n c d r e a s e
l e v e l s o f t h e = 4 N .3, K C d f A = 1( 1 , F p = 0 .0 6 3 ) wh en P BMC s were in cu b ated i n v i t for r 2o 4
h ou rs .
Individual NKCA levels (% killing at E:T ratio = 50:1)
6 0
5 0
4 0
3 0
2 0
1 0
0
NKCA ( 50: 1 rat i o)
T i me 0 24 hr s
NKCA levels (95% C.I.) by flowcytometry
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 29 - I m p e r i a l o C n o d l o n l e g e L
60
50
40
30
20
10
0
N =
1 2
Ti me 0
Fi gu r e 45a: Ind i vi d u a l N K C le A ve ls a t Fi gur e 45b: M ea n ( 95% C. I. ) N K C A l e v e l s
T i m e 0 a n d a f t e r 2 4 h o u r i n c u b a t i a t o T n i m e 0 a n d a f t e r 2 4 h o u r i n c u b a t i o n
C o n c l u s i o n :
Th e level s of th e N KC A of P BMC s afte r 2 4 h ou rs i n v i in t cu r o b at ion sh owed a tre n d
t o w a r d s i n c r e d a s l e v e l s c o m p a r e d w i t h , T i b m u t e t h 0 a t t h e i n c r e a s se h ort w a s o f s tat is ti cal
s i g n i f i c a n t .
3 .3 .1 . 2 N K -c e l l p e r c e n t a g e i n P B M C s a f t e r 2 4 h o u r s i n c u b a t i o n
H a v i n g s h o w n t h a t i n c u b a t i o n o f P B M C s f 2 o 4 r h o u r s r e s u l a t tren e d ti oward n s a n
in creas e in NK c yt ot o xi c act ivit y, th is ex p erimen t w a s p e r f o r m d e to d et er mi n e if t h is was
a s s o c i a t e d w i t h a n i n c r e a s e i n t o t a l N K -c e l l p e r c e n t a , g e p e r h a p s d u e to ad h eren ce or l os s b y
s e l e c t i v e c e l l d e a t h b-p o f p u l o t a t h e i s r o of n s Pu BMC s .
L y m p h o c y t e s -p u o b p u l a t i s o n w i t h i n P B M C s w e -c r yto e met ra y n p erfo a l rmed y s e d b y f
p r i o r a t n d o a f t e r 2 4 h ou rs c u l t u r . e
p = 0 . 0 6 3
1 2
24hrs

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Individual NK-cell percentages in PBMCs
3 0
2 5
2 0
1 5
1 0
Fi gu re 4 6 a s h ows t h at t h ere was n o c on s is ten t ch an ge in i n d ividu al level s o f total N K -c e l l
p e r c e n t a g e s P B i M n Cs a f t e r 2 4 h r s i n v i i t n r c o u b a t , i i.e. o n five in cr eas ed , f ou r d ecr eas ed an d
t h r e e s t a y e d t h e s a m e r e g a r d l e s s o f t h e i r N K C A . Figu c h a n re g e 46b s s h ows th at there was n o
s ign ifican t d i fferen ce i n t h e m e a n p e r c e n t a g e o f N K -c e l l s a fter 2 4 h rs in cu b ation .
5
0
3 0
C D 5 6 N K c e l l %
T i me 0 24hr s
CD56 NK cell% (95% C.I.)
2 0
1 0
0
N =
Fi gu r e 46a : Ind i vi d u a l NK-c e l l p e r c e n t a g e Fi gu r e 46b: M e a n ( 9 5 % C . I . NK-c ) e l l p e r c e n t a g e
i n P B M C s a t T i m e 0 a ours n d a f t e r 2 4 h i n P B M C s a t T i m e 0 a n o d u rs a f t e r 2 4 h
C o n c l u s i o n :
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 30 - I m p e r i a l o C n o d l o n l e g e L
1 2
Ti me 0
Th e t r e n d t o w a r i d s n c r a e n a s e i n N K c y t o ctivit t o x i y c in a P BMC s aft e r 2 4 h ou rs
i n c u b a t i o n w a s n o t a s s o c i a t e d w i t h a n i n c r e t a s e h e p e -c e r l l s c . e n t a g e o f N K
1 2
24hrs

Individual NKCA (% killing at E:T ratio = 50:1)
P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
3 .3 .1 . 3 N K C A aft er 2 4 h rs i n cub ation of P BMC s w i t h c o r t i s o l
T h e a i m o f t h e xp i s eri men t w a s t o e x a m i n e t h e e f f e c t o f 2 4 h o u r o s f M o f C P s i B n c u b a t i o n
with c o r t i s o l a t p h ys i ol o gi cal an d h igh er le v e l s o f N K C A . P B M C s were in cu b at ed wi th two
c o n c e n t r an d a 2 5 t 0 0 n i M ) o n f s c o r t i ( s o 2 l h o 5 f u r o 0 r s n a 2 4 n M d N K C A w a s m e a s u r e d b y
f l -c o yt w omet r y. Du e t tech o n ical p r o b l e m s n , e s o a m p l e f r o m o n e v o l u n t e e was r l o st to th e s tu d y,
s o that res u l t s fr om 1 1 s amp les wer e an al ys ed .
6 0
5 0
4 0
3 0
2 0
1 0
Fi gu re 4 7 a s h ows i n each i n d ivid u al th e effect of e xp os u re of P BMC s t o c orti s ol (2 5 0 an d
2 5 0 0 n M ) on th e level s o f th e N KC A. Fig u re 4 7 b s h o w s a d e c r e a s e i n a t n h l e v m e l e of th e
N K C A w h e n c o rt i s o l w a s p r e s e n t. T h e r e p e a t d e meas u re ANOV A s h ow ed a s ign if ican t
d e c r e a s e i n t h e l e v e l s o f N K C A w i t = h 1 c 0 o . r 5 d0 t f = i 1s 0 o , l p = 0 c .0 o 0n 9 c ). e Th n t is r a t i o n ( F
d e c r e a s e w a s c o n f i r m e d b y p o s t-h oc p air ed t-t e s t c o m p a r i s o n s ( m e a n d i f f e r e n c e = 6 . 0 6 , s t a d n d a r
erro r = 1 .7 4 , p = 0 . 0 1 : 8 b e t w e e n th e N K C A w i t h ; an d 0 mean n M d ifferen a ce n = d w i t h
7 .0 2 , s tand ard error , 2 .1 7 , p = 0 . 0 2 : 7 b e t w e e n t h e N K ). C Th A ere w i t h 0
w a s n o s i gn i fi can t d i ffe ren ce b etween N KC A with 2 5 0 n M an d 2 50 0n M.
0
NKCA (50:1 rati o)
0 n M 2 5 0 n M 2 5 0 0 n M
NKCA levels (95% C.I.) by flowcytometry
6 0
5 0
4 0
3 0
2 0
1 0
� �
� �
� �
0 n M 2 5 0 2 n 5 M 0 0 n M
Fi gur e 47a : I ndividua l N K C A l e v e l w s i t h c o r t i s o l Fi gur e 47b: M e a n ( 9 5 % C . I . ) N K C A l e v e l s
at 0nM, 250nM, and 2500nM w i t h c o r t i s o l at 0nM, 250nM, and 2500nM
C o n c l u s i o n :
Th e in cu b at i on of P BMC s with 2 5 0 n M or m ore c o r t i s o l f or 2 4 h ou rs h a d a s u pp res s in g
effect u p on N KC A.
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 31 - I m p e r i a l o C n o d l o n l e g e L
� ��
p = 0 . 0 1 8
p = 0 . 0 2 7

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Individual NK-cell percentages
3 .3 .1 . 4 N K -c e l l p e r c e n t a g e i n P B M C s a f t 2 e 4 r h o u r s i a n c t u i b o n w i t h l c o r t i s o
3 0
2 5
2 0
1 5
1 0
H a v i n g s h own th at c ort is ol at 2 5 0 o n r M m o r h e ad a s u p p r e s s iv e effect u p on N K C A , th is
exp eri men t was p er fo rmed t o d eter min e if th is su p p res s ive effect was as s o ciated w ith a ch an ge
i n t h e p e r c e n t a g e o N f K -c e l l s i n t h e P B M C . N s K -c e l l s w i t h i n P B M C s w e -r
e a n a l y s
c y t o m e t , r py er fo rmed aft er 2 4 h ou rs in cu b ation with two c ortis ol con cen tration s (0 n M, 2 5 0 n M
an d 2 50 0n M).
Th ere w e r e n o ign s ifican t d if feren ces in t h e N K -c e l l p e r c e n t a g e i n t h e P B M C s a f t e r 2 4 h r s
i n v i in t cub r o at ion wi th cort is ol (0 n M, 2 5 0 n M an d 25 00 n M). Fi gu re 4 8 a an d Figu r e 4 8 b s h ow
i n d i v i d u a l mean a n d s level s o f tot al N K -c e l l p ercen tages in th e P BMC s , res p ectiv ely.
5
0
C D 5 6 N K c e l l %
0 n M 2 5 0 n M 2 5 0 0 n M
CD56 NK cell% (95% C.I.)
3 0
2 0
1 0
1 2
1 2
1 2
0 n M 2 5 0 2500 n nM M cortisol
Fi gur e 48a: Individua l N K -c e l l p e r c e n t a g e Fi gu r e 48b: M ea n ( 95% C. I. ) N K -c e l l p e r c e n t a g e s
wit h c ort is ol at 0nM, 250nM, and 2500nM w i t h c o r t i s o l at 0nM, 250nM, and 2500nM
C o n c l u s i o n :
Th e c o r t i s o l a s s uo pc pi res a t s e ion d of N K C A in P B M C s was n ot as s ociated wit h a
c h a n g e i N n K -c e l l p e r c e n t . a g e
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 32 - I m p e r i a l o C n o d l o n l e g e L
0
N =

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
3 . 3 . C 2 o m p a r i s o n o f t w o m e t h o d s f o r m e a s u r i n g N K c y t o t o x i c a c t i v i t y ( N K C A ) :
- the fl ow cy to me tri c meth o d a n d the c olori me tric meth o d (Cy toT o x9 6 ® ) -
T h e f l o w c y t o m e t r i c m e t h o d o f s in a g s s N e s K c y t o t o x i c a c [G t i o v d i o y-R t y ami r ez et al .,
2 0 0 0 ] was in it ial l y ad op ted to a void th e c on ven tion al r a d i -a o c t i v e
5 1 C r -r e l e a se a s s . a Howe y ver,
t h e f l o w metric c y t o met h od is lab ori ou s a n d req u ires a h igh d egree o f s kill . A s imp ler
c o l o r i m e t r i c , m e n t a h m o e d l y t h e C y t ®, o T ho as x 9 b6 een d evel op ed [ P r o m e g a , 2 0 0 4 ]. Th is
m e t h o d m e a s u r e s l e v e l s o f r e l e a d s e l a c t i c d e h y d r o g e n a s e ( L D H f ) r killed o m K 5 6 2 c e l . l Th s e
a m o u n t o f LD H i s p r o p o r t i o n a l t o t h e n u m b e r s o f k lled i K5 6 2 cel ls . Th e LD H le v el can b e
accu rat el y an d s i mp l y meas u red col ori me tricall y.
The f l o w y t c o m e t r i an c d th e col ori met ri c as s a ys were co mp ared in th is exp erimen t.
P BMC s were s ep arat ed f ro m 4 5 h ealth y i n d ivid u als and NKC A an al ys ed , in p arall el , b y both
the f -c l y t o m w e t ri c an d the c o l o r i m e t r i c s. m e t h o d
Fi gu re 4 9 s h ows t h e s cat t er g rap h of th e c orrelati on b etween th e two meth od s . Th e
P ears on correl at i on an al ys i s s h ows th at th ere is a s i gn ifican t co rrelati on b etween th e two
m e t h o d s ( r = 0 -tailed . 3 6 7 , p = 2 0 .0 1 3 ).
NKCA by CytoTox (LDH) assay
60
50
40
30
20
10
0 Rsq = 0.1349
0 10 20 30 40 50 60
NKCA b y f l o wc yt o me t r y a s s ay
Fi gur e 49: C o r r e l a t i -c o n y t b o e m e t w e r e y n m f e -r t l e h o l o w e d a s a i n n d g L D m H e t h o d o f t h
C o n c l u s i o n :
p = 0.013
n = 45
r = 0.367
It was d et er mi n ed th at th e levels o f th e N KC A s h o u l d b e meas u red b y th e les s lab o riou s
b u t s t i l l v a l id col ori met ri c meth od in s u b s e q u e n t exp erimen ts an d to rep eat th e p rev iou s
e x p e r i m e n t s w i t h a l a r g e r s a m t p h pe l revi e ou s fi s n d i in gs z . e t o c o n f i r m
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 33 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
3 . 3 . 3
In v e s t i g a t i o n o f N -c K e l l p r o f i l ae nd s N K C A (c o l o r i m e t r i c ) m e t h o d
T h e f l o w c y t o m e t Cr A i s h ow c ed a th at s in s cu e b at s ion s m of e P BMC n t s fo o r 2f 4 h ou N rs K
res u lted i n i n creas ed NK c yt ot oxicit y. Th is rep eat exp eri men t was p erf or med with P BMC s fro m
a larg er n u mb er of vol u n t eers u s in g th e c olori metric meth od with th e ob jective of c o n f i r m i n g
th es e res u l t s .
3 .3 .3. 1 N KC A, a s s e s s e d b y c o l o r i m e tri c m e t , h o a d f t e r i n c u b a t i o n o f P B M C s f o r 2 4 h o u r s
P BMC s were ob tai n ed fr om 3 1 h ealth y s u b jects a n d i n c u b a t e d f o r rs 2 p4 rior h o tu o
as s es s in g th e NKC A a t effect or : tar get rat ios o f 5 0 : 1 a n d 2 b 5 y : 1 t h e c o l o r i m e t . r i c a s s a y
I nd ivid u al an d mean ( 9 5 % C . I . ) N KC A l evel s wi th ef fect o r : tar get ratios of 5 0 :1 a n d 25 :1
p re an d p os t in cu b at ion are s h own in Fig u re 50 ( a ) , ( b ) an d Fi gu re 51 ( a ) , ( b , ) res p ect ivel y. In
a g r e e m e n t w i t h p r e v i o u s f i n d i n g s , t h e r e w a s a e s mean i g n i Nf KC i c A a n lt e vel i n c r e a s e i n t h
a f t e r i n c u b a t i n g P B M he C s r f e o r p e 2 a 4 t h e o d u r s m . e s a h s T s t o h a u w t r th e e level A s oN f O V A
N K C A w e r e i n c r e a s e d a f t e r 2 4 h r s a 5i 0 n :1 c u rat b a io t ( i mean o n i d in fferen ce = 6 . 3 8 (1 5 .67 to
2 2 .05 ), s d = 1 4 .9 , p = 0 .0 2 4 , t = 2 . 3 8 , d f = 3 0 ) a n d 2 5 1 : rati o ( mean d iffe ren ce = 1 0 .4 7 (8 .78 to
1 9 .25 ), s d = 1 1 .1 , p < 0 .0 0 1 , t = 5 .3 2 , d f = 3 0 ).
Individual NKCA (% killing at E:T ratio = 50:1)
5 0
4 0
3 0
2 0
1 0
0
Ti me co u r s e o f NKCA 5 0 : 1
T i me 0 2 4 h o ur s i n c uba t i o n
Mean (95% C.I.) NKCA levels at E:T = 50:1
4 0
3 0
2 0
1 0
0
p = 0 . 0 2 4
T i m e 0 A f t e r 2 4 h o u r s
Fi gu r e 50a: Ind i vi d u a l N K C (50:1) A l e v e l s Fi gu r e 50b: M e a n ( 9 5 % C . I . ) N K C (50:1) A l e v e l s
(% k i l l ) i a t n Ti g m e 0 a n d a f t e r 2 4 h r s i n c (% u b a killin t i o g) n a t Ti m e 0 a n d a f t e r 2 4 h r s i n c u b a t i o n
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 34 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Individual NKCA (% killing at E:T ratio = 25:1)
5 0
4 0
3 0
2 0
1 0
0
Ti me c o u r s e o f NKCA 2 5 : 1
T i me 0 2 4 h o ur s i n c uba t i o n
Mean (95% C.I.) NKCA levels at E:T = 25:1
40
30
20
10
0
T i m e 0 A f t e r 2 4 h o u r s
Fi gu r e 51a: Ind i vi d u a l N K C (25:1) A l e v e l s Fi gu r e 51b: M e a n ( 9 5 % C . I . ) N K C (25:1) A l e v e l s
(% k i l l ) i a t n Ti g m e 0 a n d a f t e r 2 4 h r s i (% n c u killin b a t i g) o an t Ti m e 0 a n d a f t e r 2 4 h r s i n c u b a t i o n
C o n c l u s i o n :
T h e c o l o ri met ri c as s a y res u l ts c o n f i r m e d p r e v i o u s f l o w c yt o m e t r i c f i n d i n g s t h a t
in cu b at i on of P BMC s for 2 4 h ou rs lead s to a s i g n i f i c a n t i n c r e a se in th e level s of N KC A.
3 .3 .3. 2 R e p e a t a s s e -c e s l l s m p e r c n e n t a g n e d o e f x a m i N n a K t i o n o f N K s u b p o p u l a in t i o n s
P B M C s af t e r 2 4 h o u r s i n c u b a t i o n
Alth ou gh p re vi ou s res u l t s s h owed n o as s ociation b etween th e in creas e in N KC A a fter 2 4
h o u r s i n c u b a t i o -c e n l l ( C o D f 3 P B M C s a n d N K
- C D 5 6 + ) p e r c e n t a g e s , t h e a s s o c i a t i -o
n w a s r e
e x a m i n e d p r e a n d p o s t 2 4 h o u r s i n c u b a t i o n w i t h t h ed i s nu i mb n c r er e a of s s u b ject s . In ad d ition ,
th e d is t ri b u t i on of NK cel l s acc ord in g t o t h e level of e xp res s ion o f C D5 6 an d C D16 was
e x a m i n e d . T h e l e v e l o f e x p r e s s i o n m o a r f k e t rs h can e s e b e u s ed to d efi n e c yt oto xic an d
r e g u l a -c t e l l o s . r H o y w e v e N r K , d u e t o t e c h n i c a l p rob lems with th e flow c yt omete r, on l y th e las t
1 6 s u bj e c t s f r o m t h e were a b o v an e al 3 ys 1 ed .
p < 0 . 0 0 1
Fi gu re 52 (a), (b) an d (c) s h ow m e a n ( 9 5 % C . I . pe ) r c e n t a g e s o f N K -c e l l s (C D 3 - C D 5 6 + )
w i t h s u b p o p u l a t i o n s o cf yt oto xi c N K -c e l l s (C D 3 - d i m
C D 5 6 C D 1 6 + ) an d regu lat or y N K -c e l l (C D 3 -
C D 5 6 b r i g h t C D 1 6 - ) in th e P BMC s at Ti m e 0 a n d a f t e r 2 4 i h n r c s u b a t i o n , r e s p . e Th c t ere i v we l ere y
no s i g n i f i c a n t d i f f N e K r -c e n e c l l e ps r of i il es n b et ween Time 0 a n d rs 2 4 h a f t e r in cu b at ion .
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 35 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Total CD56+ NK cell% in PBMCs
40
30
20
10
0
N =
1 6
Time 0
1 6
I ncubated 24hr s
Cytotoxic NK (CD56dim)% in PBMCs
40
30
20
10
0
N =
1 6
Ti me 0
1 6
Inc ubat ed 24hr s
1 6
I ncubated 24hr s
F i g u r e 52a: N K (%) i n P B M C s Fi gu r e 52b: C y t o t o x NK i c (%) Fi gur e 52c: R e g u l a t N o r K y (%)
a t Ti m e 0 a n d a f t e r 2 4 h r s a t Ti m e 0 a n d a f t e r 2 4 h r s a t Ti m e 0 a n d a f t e r 2 4 h r s
Fi gur e 52: P e r c e n t a -c g e l l e i n s t o t a l o a f n d e N a K c h s u b s e t a t T i m e 0 a n d a f t e r 2 4 h o u r s i n c u b a t i
C o n c l u s i o n :
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 36 - I m p e r i a l o C n o d l o n l e g e L
Regulatory NK (CD56bright) cells% in PB
40
30
20
10
0
N =
1 6
Time 0
Th e in creas e i n N K c yt ot oxi c activit y in P BMC s after 2 4 h ou rs in cu b ation was n ot
a s s o c i a t e d w i t h i n e c a r s e s i n t h e p e r c e n t a g e o N f K -c e l l s or al terat i on in th e c y t o t o x i / c re gu lat or y
N K -cell s u b p o p u l a t s . i o n
3 .3 .3. 3 Ex p r e s s i o n o f N a l t C u r y a t o t o x i c R e c e p t o r s N ( k p 4 6 a n d N k p 3 0 ) b y c yt ot oxi c N K -c e l l s
( C D 3 - d i m
C D 5 6 C D 16 + ) p re an d p os t 2 4 h o u r s i n c u b a t i o n
Ha vin g s h own t h at t h e i n creas e in N KC A in P BMC s after 2 4 h ou rs in cu b ation was n ot
as s ociat ed wi t h i n creas es i n th e p ercen tag e of total N K -c e l l s or c yt oto xic an d re gu lator y N K -
c e l l s , th is exp eri men t was p e r f o r m e t o d d etermi n e if th e in creas e in N KC A was as s ociated with
a n i n c r e a s e i n t h e e x p r e s s i o n o f t h e N a t u r a l C y t o t o x i c 0 ) R on e c th e e p t o r s ( N k p 4 6 a n d
c ytot oxi c N K -c e l l s . Th e e xp res s ion ( m e a n f l o r e s c e n t i n t e n s i t y : m . f of . i . th ) e N kp 4 6 (maj o r
c y t o t o x i c r e c e p t o r ) o n c y t o t o x i c N C K D ( 3 - d i m
C D 5 6 C D 1 6 + ) c e l l s w i t h e h s a i m e n P B M C s
1 6 h e a l t h y s u b j e c -c t y t o s m e t r w y e p e r f o e r m e d a p n r i o a tr o l cu y lt us re e a n d aft er b 2y 4 f l o w
h ou rs .
Fi gu re 53 ( a ) a n d ( b ) s h ow th at th ere was a s ign ifican t in creas e ( +4 4 % ) in th e exp re s s ion
of th e N kp 4 6 on c yt ot oxi c N K -c e l l s a f t e r 2 4 h r s i n v i t i r n o c u b a ep t eated i o meas n u( res R
ANO V A: F = 3 8 .1 , p < 0 . 0 0 1 , n = 1 6 ; m e a n d i en f f e ce r = 2 7 .0 , s e = 4 .4 ). Fi gu re 5 4 ( a ) a n d ( b )
s h o w t h a t t h e r e w a s a s i g n i f i c a n t d e c r e a -2 s e 2 % ( ) in th e exp res s ion of th e N kp 3 0 on c yt oto xic
N K -c e l l s a f t e r 2 4 h r s i n v i in t cub r o at ion (F = 1 8 .0 , p = 0 .0 0 1 , n = 1 6 ; mean d iffe re n ce = 5 .4 , s e =
1 .3 ).

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Nkp46 m.f.i. on Cytotoxic NK-cells
Nkp30 m.f.i. on Cytotoxic NK-cells
1 4 0
1 2 0
1 0 0
8 0
6 0
4 0
2 0
0
Nk p 4 6 m.f .i. o n Cy to to x ic NK cells
Ti me 0 2 4 h r s
N k p 4 6 m .f.i. o n C y to to x ic N K cells
Fi gu r e 53a: Individua l Nkp46 (m.f.i.) Fi gu r e 53b: M ea n ( 95% C. I.) N k p 4 6 ( m . f . i . )
a t Ti m e 0 a n d a f t e r 2 4 incubation h r s
a t Ti m e 0 a n d a f t e r 2 4 incubation h r s
1 4 0
1 2 0
1 0 0
8 0
6 0
4 0
2 0
0
C o n c l u s i o n :
Nk p 3 0 m.f .i. o n Cy to to x ic NK cells
T i me 0 2 4 h r s
N kp 30 m .f.i. on C y to tox ic N K cells
1 25
1 00
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 37 - I m p e r i a l o C n o d l o n l e g e L
75
50
25
0
125
100
75
50
25
0
N =
N =
1 6
1 6
Time 0
Ti me 0
Fi gu r e 54a: Individua l N k p 30 ( m . f . i . ) Fi gur e 54b: M ea n ( 95% C. I. ) N k p 30 ( m . f . i . )
a t Ti m e 0 a n d a f t e r 2 4 incubation h r s
a t Ti m e 0 a n d a f t e r 2 4 incubation h r s
T h e s e r e th s at u th l e it n creas s e is n NKC h o w A in P BMC s aft er 2 4 h ou rs in cu b ation was
a s s o c i a t e d w i t h a n i n c r e a s e i n th e exp res s ion of Nkp 4 6 on c yt oto xic N K -cell s , an d it w a s a l s o
as s ociat ed wi th a d e c r e a s e i n t h e e x p r e s s i o n alth o f ou N gh k p t3 h0 e amp li tu d e of th is d ecreas e
w a s s m a l l.
p < 0 . 0 0 1
1 6
24hr s
p = 0 . 0 0 1
1 6
24hrs

Individual NKCA (% killing at E:T ratio = 50:1)
P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
3 .3 .3. 4 N KC A, a s s e s s e d b y c o l o r i m e tri c m e t , h o d a f t e r 2 4 h o u ation r s i of n Pc BMC u b s wi t h
250n M c o r t i s o l
T h i s e x p e r i m e n t a i m t e h pe d revi ou t s exp o eri mc en o t 3 n . f 3 . i 2 b. y r 3 m t h e r e
u s in g a col o ri met ri c m et h od with a lar ger n u mb er of s u b j ects , i.e. to d ete rmin e if 2 4 h rs
in cu b at i on of P BMC s wi t h 2 5 0n M cortis ol in h ib its an in creas e in th e level s of th e NKC A.
P BMC s fro m 3 1 h eal t h y s u b jects were in cu b ated for 2 4 h ou rs with or with ou t 2 5 0 n M
c o r t i s o l p r i o r t o a s s e NKC s s i n A g bt y h t e h e col ori met ri c meth od a t ef fecto r : tar get ratios o f b oth
5 0 : 1 a n d 2 . 5 : 1
I n d i v i d u a l ( a m ) e a n a n ( d b ) N K C A l ls e after v e exp os u re of P B MC s to c ortis ol are s h own
in Figu re 5 5 ( a ) , ( b ) an d 56 ( a ) , ( b ) . A s p f r o e u v n , i d th o ere u s l was y a s ign ifi can t re d u ction
f o l l o w i n g e x p o s u r e o f P B M C s t o 2 5 0 n M o f c o r t i s o l in th e mean N KC A l evels at ef fector : tar get
r a t i o = 5 0 (m : 1 e a n di f f e r e n c e = , SD 6 . = 6 6 9 .9 , p < 0 .0 0 1 , t = 5 . 4 1 , d ) f a n = d 3 2 0 5 : (mean 1
di f f e r e n c e = , SD 9 . = 7 8 3 .1 , p < 0 .0 0 1 , t = 6 . 6 6 , d f = 3 0 , re ) s p e c t i v e [F l i y g u r e 5b 5 an d Fi gu re
56b] .
50
40
30
20
10
0
NKCC % ( LDH a s s a y) 50:1
0 n M 250nM cortisol
Wi t hout dr ugC o r t i s o l 2 5 0 n M
NKCA levels (95% C.I.) 50:1 ratio
40
30
20
10
Fi gu r e 55a: In d i v i d u a (50:1) l lev N e K l C s A Fi gur e 55b: M e a n ( 9 5 % (50:1) C . I l . e v ) e l s N K C A
(% killin g) of P BM Cs in c uba te d (% killin g) o f P B M C s i n c u b a t e d
w i t h o r wi t h o u t c or t i s o l w i t h o r w i t h o u t l c o r t i s o
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 38 - I m p e r i a l o C n o d l o n l e g e L
0
N =
3 1
p < 0 . 0 0 1
3 1

Individual NKCA (% killing at E:T ratio = 25:1)
P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
5 0
4 0
3 0
2 0
1 0
0
NKCC % ( LDH a s s a y) 25: 1
0 n M 250nM cortisol
Wi t ho ut d r u gC o r t i s o l 2 5 0 n M
NKCA levels (95% C.I.) 25:1 ratio
Fi gu r e 56a: In d i v i d u a (25:1) l l e N ve K ls C A Fi gur e 56b: M ea n ( 95% C. I. ) NKCA (25:1) l e v e l s
(% killin g) o f P B M C s i n c u b a t e d
(% killin g) o f P B M C s i n c u b a t e d
w i t h o r wi t h o u t c or t i s o l w i t h o r w i t h o u t l c o r t i s o
C o n c l u s i o n :
40
30
20
10
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 39 - I m p e r i a l o C n o d l o n l e g e L
0
N =
I n c u b a t i o n o f P B M C s f o r 2 4 h o u r s w i t h c o r t i s o l ( 2 5 0 n f M N) KC c A. a u s e s a n i n h i b i
3 .3 .3.5 NKC A l e v e l s b e t p w r e e a n d p o s t 2 4 h o u r in s cu b at ion wi th o r w i t h o u t 2 5 0 n M c o r t i s o l
H a v i n g s h o w n t h a t t h e r e w a s a n i n c r e a s e i n t h e l e v e l s o f N p K < C A 0 .0 ( 0 1 , n = 3 1 )
follo wi n g i n v i cu t r ltu o re of P B MC s fo r 2 4 h ou rs ; an d th at th e add ition of 2 5 0 cortis n M ol t o th e
c u l t u r e m e d i u m i n h i b i t e d (p t h i < s 0 . r i 0 0 s 1 e , n = 3 1 as ) s, ociat t h ie on b et ween th es e d egree of
the i n c r e a s e s a n d t h e i n h i b i t i no alys n w ed e . r e a
Th e in d ep end en t t-t es t s s h owed th at th e NKC A l evels of th e P BMC s b ef ore 2 4 h o u rs
i n c u bat i on were n ot d i fferen t f ro m th e le vels o f P BMC s afte r 2 4 h ou rs of in cu b ation with
2 5 0n M cort i s ol [F i g u r e 5 7].
3 1
p < 0 . 0 0 1
3 1

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
C o n c l u s i o n
NKCA 25:1 ratio (95% C. I.)
30
20
10
0
N =
3 1
Ti me 0
3 1
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 40 - I m p e r i a l o C n o d l o n l e g e L
3 1
24hr s No dr 24hrs ug Cortisol
Fi gu r e 57: M ea n (95% C. I .) of th e NKCA a t T ime 0 a nd aft e r 24 hr s in cu bat io n of P BM Cs
w i t h / o u t 2 5 0 n M c o t r i s o l i n t h e t a r g e t : e f f e c t o r r a t i o o f 2 5 : 1
Th e d egrees of an i n creas e i n N KC A le ve l after 2 4 h ou rs o f in cu b ation an d an in h ib ition
of th is i n creas e i n N KC A of th e P BMC s in cu b ated with 2 50 n M cortis ol a re s tati s ticall y th e
s ame.
Th is fin d in g w a s a l s o e d b c y o c n o r f r e i l a r t n a i l m o y n s s, e in wh ich th e as s oci at ion b etween
time c h a n g e s ( a f t ho e u r s 2 i n 4 c u b a t i o n w i t h o u t c o r t i s o l - T i m e 0 ) an d d i f f e r e n c e s (afte r 2 4
h ou rs i n c u b a t i w o i n t h o u t cort is ol – with c o r t i s o l) b o th a t t h e r a t i o o f 5 0 : p 1 = ( 0 .0 4 2 , r = 0 .3 7 , n
= 3 1 ) a n d 2 5 : 1 p ( < 0 . 0 0 1 , r = 0 . ) 7 [Fi 2 , gu re n 5 = 8 ]. 3 1
Increase in NKCA 25:1 (24h - Time 0)
40
30
20
10
0
p < 0.001
N o t s i g n i f i c a n t
p < 0.001
p < 0 .0 0 1
n = 3 1
r = 0 . 7 2
- 10 Rsq = 0.5220
- 30 - 20 - 10 0 10 20 30
Reduction of NKCA 25:1 (No-drug - Cortisol)
Fi gur e 58: C o r r e l a t i o n s b e t w e e n t h e c h a n g e s a n d d i f f e r e n c e s o f t h e N K % C A killin ( g: be t we e n a t
T ime 0 a nd aft e r 24hr s incubat io n of P BM Cs wit h / out 2 5 0 n M c o r t i s o l i n t h e ) r a t i o o f 2 5 : 1

NK-cells (%) in PBMCs
P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
C o n c l u s i o n :
Th e d egree of in h ib it ion in th e NKC A b y th e i n v i t e r x o p os u re to th e 2 5 0 n M cort is ol was
a l m o s t t h e s da eg m e ree of in creas e in th e levels o f N KC A a fter 2 4 h ou rs i n v i incu t r o b at ion of
P BMC s .
3 .3 .3.6 C D 5 6 K-c N e l l s u b s e t p r o f i l e s i n P B M C s a f t e r 2 4 h o u r s i n c u b a t i o n w i t h 2 5 0 n M c o r t i s o l
Ha v i n g c o n f i r m e d i n t h e l a r g e r c o h o r t o f s u b j e c ts t h a t 2 4 h o u r s i n with c u b a cor t i ti so ol n
in h ib ited NKC A, th e e xp eri men t t o d eter min e if th is was d u e to a ch an ge in N K -c e l l p e t r a c g e n
was rep eat ed . In ad d i t i on , N K -c e l l s u b s e t p r o f i l e s (p e r c e n t a g e s of c yt oto xic an d re gu lator y N K -
c e l l s w i t h ) i w n e r e t h e x e a m . i Du P n B e M d to C tech n ical p rob lems in fl ow c yt om eter, on l y th e
las t 1 6 s ub j ect s from t h e ab ove 3 1 s u b jects were an al ys ed .
F i gu re 5 9 ( ), a (b) a n (c) d s h o (a) w mean ( 9 5 % C .I.) p e r c e n t a g e s o f N -c K e l l ( C D 3 - C D 5 6 + ),
(b) c yt ot o xi c N K -c e l l ( C D 3
- d i m
C D 5 6 C D 16 + ) an d (c) re gu lat or y N K -c e l l ( C D 3
- C D 5 6 b r i g h t C D 16 - )
in th e P BMC s aft er 2 4 h o u r s i n c u b a tion w i t h a n d w i t h o u t 2 5 0 n M c o r t i s o l y. , As r e s fou p e nc d t i v e
p r e v i o u s l y, th e r e w e r o e s i gn n ifi can t d iff eren ces i n -c e N l K l p e r c e n t a g e s a n d s u b p o p u l a t in i o n s
P B M C s a f t e r 2 4 h r s i n c u b a tion w i t h a n d w t i 2 5t 0n h o M u cort is ol .
Total NK (CD56) cell% in PBM Cs
40
30
20
10
0
N =
1 6
No dr u g
1 6
Cortisol
Cytotoxic NK (CD56dim ) cell% in PBM Cs
40
30
20
10
0
N =
1 6
No dr ug
1 6
Cortisol
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 41 - I m p e r i a l o C n o d l o n l e g e L
Regulatory N K (CD 56bright) cell% in PBM
40
30
20
10
0
N =
1 6
No dr ug
F i g u r e 59a: N K (%) i n t h e P B M C s Fi gu r e 59b: C y t o t o x NK i c (%) Fi gur e 59c: Re gula t or y N K (%)
a f t e r 2 4 h r wi s t h / o ut co r t i s o l a f t e r 2 4 hr s wi t h / o ut co r t i s o l a f t e r 2 4 hr s wi t h / o ut co r t i s o l
Fi gur e 59: P e r c e n t a -c g e ll e in s t ota l o a nd f e a ch N K s ubs et in th e P BM Cs a ft er 24 ho urs in cu ba t io n wit h
a n d wi t h o u t 2 5 0 nM c or t i s o l
C o n c l u s i o n :
Th e c o r t i s o l a s s o c s i u a t p e p d r e s s i in P o B n M C s o a f t e N r K C 2 4 A h o u r s i was n c u b a t i o n
n ot as s oci at ed wi th a c h a n g e N i K n -c e l l r o f p i l es.
1 6
Cortisol

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
3 .3 .3.7 E x p r e s s i o n y o t f o t N a o t x u i r c a l R e C c e p t o r s ( N k p -c 4 ells 6 a n d N k p 3
( C D 3 - C D 5 6 d i m C D 1 6 + ) a f t e r 2 4 h o u r s i n cu b a t i o n w i t h o r w i t h o u t 2 5 0 n M c o r t i s o l
Ha vin g s h own t h at t h e i n h i b ition of an in creas e in N KC A in P BMC s afte r 2 4 h ou rs
i n c u b a t i o n w i t h 2 5 0 n M c o r t i s o l w a s o c n o i t a t a s e s d w i c h t a h n g e s th i e n p ercen tage d is tri b u ti on s
of t otal or c yt ot oxi c N K -c e l l s , th is exp eri men t was p erf or med t o d e t e r m i n e i cf ortis t h ol e
i n d u c e d in h ib iti on wa s a s s o c i a t e d w i t h t h e e x e p r m e s a s j i o r o n c o y f t o t h o x i c r e c e p t o r o n
c ytot oxi c N K -c e l l s. In e x p e r i m e n t 3 . 3 . 4 . 3 , was t h i s h own to b e in creas ed aft er 2 4 h ou rs
in cu b at i on .
Th e exp res s ion ( m e a n f l o r e s c e n t i n t e n s i t y : m . f of . i . th ) e Nkp 4 6 an d th e Nkp 3 0 on
c y t o t o x i c N K C ( D 3 - d i m
C D 5 6 C D 1 6 + ) cel ls wi th in P BMC s from 1 6 h ealth y s u b jects were
a n a l y s e d b y w-c f yt l o om et r y p e rf or med af ter 2 4 h ou rs in cu b ation with or with ou t 2 5 0 n M
cortis ol .
Fi gu re 60 ( a ) a n d ( b ) s h ow th at th ere was a s ign ifican t in h ib ition of an in creas e in t h e
exp res s ion of th e Nkp 4 6 on c yt oto xic N K -c e l l s a f t e r 2 4 h r s i n v i t i r n o c u b a e p t e a i t ed o n ( R
meas u res ANOV A: F = 5 8 .4 , p < 0 .0 0 1 , n = 1 6 ; mean d ifferen ce = 1 3 .3 , s e = 1 .7 ). Fi gu re 61 (a)
a n d ( b ) s h ows t h at t h ere was a s ign ifican t , b u t s ligh t d ecreas e in th e exp res s ion o f t h e Nkp 3 0 on
c ytot oxi c N K -c e l l s a f t e r 2 4 h r s i n v i incu t r bo at ion (F = 1 3 .2 , p = 0 .0 0 2 , n = 1 6 ; me an d ifferen ce
= 2 . , s3 e = 0 .6 ).
1 4 0
1 2 0
1 0 0
8 0
6 0
4 0
2 0
0
Nk p 4 6 m.f .i. o n Cy to to x ic NK cells
N o d r u g Co rtiso l
N k p 4 6 m .f.i. o n C y to to x ic N K cells
1 25
1 00
75
50
25
0
N =
p < 0 . 0 0 1
1 6
No d r u g
Fi gur e 60a: M e a n ( 9 5 % C . I . ) N k p 4 6 ( m . f . i . ) Fi gur e 60b: Individual Nkp46 (m.f.i.) a f t e r
a f t e r 2 4 hr s i n c ub at i o n o f P B M Cs wi t h / o u t c or t i s o l 24 hrs in c uba t io n of P BM Cs wi t h / ou t c o r t i s o l
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 42 - I m p e r i a l o C n o d l o n l e g e L
1 6
cortisol

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
1 4 0
1 2 0
1 0 0
8 0
6 0
4 0
2 0
0
Nk p 3 0 m.f .i. o n Cy to to x ic NK cells
N o d r u g Cortisol
N k p 3 0 m .f.i. o n C y to to x ic N K c e lls
Fi gur e 61a: M e a n ( 9 5 % C . I . ) N k p 3 0 ( m . f . i . ) Fi gu r e 61b: T h e i n d i v i d u a l N k p 3 0 ( m . f . a i f . t e ) r
a f t e r 2 4 hr s i n c ub at i o n o f P B M Cs wi t h / o u t c or t i s o l 2 4 h r s i n c u ba t i o n o f P BM C s wi t h / ou t c o r t i s o l
C o n c l u s i : o n
T h e s e r e s u l t s u gges t th at th e in h ib it ion of an in creas e in N KC A in P BMC s afte r 2 4 h ou rs
in cu b at i on wi t h cort i s ol was as s ociated w ith an in h ib ition of an in creas e in th e e xp res s ion of
Nkp 4 6 on c yt ot oxi c N K -c e l l s .
3 .3 .3. 8 Nkp 4 6 exp res s ion on c yt oto xic NK-c e l l s p r e a n d p o s t 2 4 h o u r in s cub at ion wi th o r
w i t h o u t 2 5 0 n M c o r t i s o l
12 5
10 0
7 5
5 0
2 5
0
N =
p = 0 . 0 0 2
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 43 - I m p e r i a l o C n o d l o n l e g e L
1 6
No dr u g
Ha vin g s h own t h at t h ere w as an in creas e in th e exp res s ion s of N kp 4 6 (m.f .i.) on th e
c ytot oxi c N K -c e l l s (p < 0 . 0 , 0 1 n = ) f ol 1 6 lowi n g i n v i cu t r ltu o re of P BMC s fo r 2 4 h ou rs ; an d
that the ad d it ive of 2 5 0 cortis n M ol t o th e cu lt u re med iu m in h ib ited th is in creas e, th e d egree of
th es e in creas es an d t h e i n hi b ition were an al ys ed . Th e in d ep en d en t t-tes t s s h owed th at th e
e x p r e s s i o n o f N k p 4 6 -c e l ( l s m . b e f o . r e i 2 . 4 ) h o u r o s n wer i n e c u lowe b y a t r i to ho an t o x i c N K
t h a t o n -cells c y t aft o e r t 2 4 o h ou x i rs of c in cu N bK ation with 2 5 0n M cortis ol [F i g u r e 62].
1 6
cortisol

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Nkp46 m.f.i. on Cytotoxic NK cells
125
100
75
50
25
0
N =
1 6
Time 0
1 6
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 44 - I m p e r i a l o C n o d l o n l e g e L
1 6
24hr s No dr 24hrs ug cortisol
Fi gur e 62: M e a n ( 9 5 % C . I . and ) individual expression of N k p 4 6 ( m . f . i . -c ) e lls o n t h e c y t
( C D 5 6 dim CD16 + ) a t T i m e 0 a n d a f t er 2 4 hr s i nc u b at i o n of P B M Cs wi t h / o ut 2 5 0n M c o r t i s o l
C o n c l u s i o n :
Alth ou gh t h ere was an i n creas e in th e e xp res s ion s of N kp 4 6 (m.f .i .) on th e c ytot oxi c N K -
c e l l s f o l l o w i n g 2 4 h o u r s i , th n c e u ad b a dt it i on o n of 2 5 0 cortis n M ol in h ib it ed t h i s r . i Th s e is
in h ib iti on d i d n ot reach comp lete s u p p res s ion .
3 .3 .3.9 NKC A an d Nkp 4 6 exp res s ion on c yt oto x ic N K -c e l l s p r e a n d p o s t 2 4 h o u r in s cub ati on
with o r w i t h o u t 2 5 0 n M c o r t i s o l
Ha v i n g t h e d i s c r e p a n c y b e t w e e n t h e c h a n g e s i n N KC A l e v e l s a n d c h a n g e s n i th e Nkp 4 6
e x p r e s s i o n p - r a e n d p o s t- 2 4 h ou rs in cu b at ion with or with ou t 2 5 0 n M corti s ol , th e s ame 1 6
volu n teers wh os e N kp 4 6 were ex amin ed ou t of th e 3 1 s u b j e c t s w e r -an e r al e ys ed ac cord in g to their level s of N KC A. A t ren d of ch an ges th at were s imil ar t o e t res h u lt s in Nkp 4 6 an al ys es w as
ob tain ed i n t h i s an al ys i s of N KC A levels . Alth ou gh th ere was an in creas e in th e le vel s o f
N K C A (p < 0 . 0 0 1 ) foll owi n g i n v i cu t r ltu o re of P B MC s fo r 2 4 h ou rs , an d th e ad d ition of
2 5 0 cortis n M ol t o th e cu lt u re med iu m in h ib ited th is ris e, th is inh ib ition d id n ot reac h comp lete
s u pp res s ion [F i g u r e 3]. 6
p < 0.001
p < 0.001
p < 0.001

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Means (95% C.I.) of NKCA in 25:1 ratio
40
30
20
10
0
N =
1 6
Ti me 0
1 6
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 45 - I m p e r i a l o C n o d l o n l e g e L
1 6
24hr s No dr 24hrs ug cortisol
Fi gur e 63: M ea n (95% C.I .) and in divid ua l le ve l of NKCA a t T ime 0 an d af te r 24 hr s in c uba t io n of
P BM Cs wit h / out 250nM c or t iso l a t t a r g e t f : f e c t o r r a t i o o f 2 5 : 1
C o n c l u s i o n :
Th e in h ib it ion of an in creas e in N KC A le vels afte r 2 4 h rs i n v i in t cub r o at ion wi th 25 0 n M
c o r t i s o l h a s a s s o c i a t i o n w i t h t h -cells e i aft en r h i b i t i o n
th e 2 4 h rs i n cu b at i on .
3 . 3 . 4 E n d o g e n o u s s t r e s s h o r m o l n e v e ls a n d N K C A ( c o l o r i m e t r i c m e t h o d )
Ha vin g s h o w n t h a t e x p u o r s e o f P BMC s t o ex o gen ou s cortis ol f or 2 4 h ou rs ap p ear ed to
b lock t h e cu l t u re as s oci at ed ris e in th e lev els of N KC A, t h e le vels o f en d ogen ou s c ortis ol in th e
p l a s m a o f s u b ject s was meas u red to d eter min e if p rio r in vivo exp os u re af fected N KC A le vel s .
I n a d d i t i o n , t h -S e a n p d l m a e l s a m t o a n i n l w e r v e a l s in o ord m o e er f a s to u r D e d H E A
examin e th e h yp ot h es is th at p rior in vivo ex p o s u r e t o e i t h e r o f A t h e m i s a s
l e v e l h e s . p l a s T m s a f r o m t h s e p a r a t P B e d M C s wer e an al ys ed to meas u re en d oge n ou s levels of
c o r t i s -S o l a n , d m D e l H a E t A bo y n i E LIS n A as s a ys . C o rrel at i on an al ys es b etween e n d ogen ou s
l e v e l s o f s t r -a e s s s o c i a t e d h o r m -S o n e a s n d ( c m e o l r t a KC t i A o s level n o i l s n we , ) re D a H E n A d N
u s ed to t es t t h e h yp ot h es i s .
p < 0.001 p = 0.001
p = 0.012

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
3 .3 .4.1 En d o g e n o u s h o r m o n e a t T i l m e e 0 v p o e i n l t s a n d N K C A
A t T i m e 0 p o i n t , t o h se ign r e ifi can w a t s correl n at ion b et ween e n d o g e n o u s c o r t i s o l l evels
an d NKC A le vel s at b ot h an al ys es ratios of 5 0 : 1 ( r = , n . = 0 39 1 , n s ) a n d 2 5 : 1 (r = - . 0 , 1 n = 3 1
n s ). D H E -S A l e v e l s , o n t h e o t h e r h a n d , h a d a s i g n i f i c a n t p o s i t i v e c o r r e l a t i o n w i t h N K C A l e v e l
b u t o n l y a t t h e r a t i o o f , n 2 = 5 3: 1 , p ( = r 0 . = 0 ), 3 . a n 3 d 8 n ot wi th th e level s at th e ratio of 5 0 :1
( r = , . n 1 = 9 3 1 , n s). o s ign N ifi can t c or rel at ion b et ween e n d o g e n o u s m e l a t lev o n i els n an d
NKC A l evel s at th e rat io o f 5 0 : 1 ( r = - . 0 , n 9 = 3 1 , n s) a n d 2 5 : 1 (r = - . 0 , n 3 = 3 1 , n s) was fou n d
a t T i m e 0 p o i n t.
C o n c l u s i o n :
Th es e res u l t s s u gges t t h at p rior in vi vo ex p o s u r e t o c o r tis ol or melat on in d id n ot aff ect
NKC A l evel s at th e Ti me 0 p oin t, alth ou gh t h e r e i still s a p os s ib il it y th at p ri o r in v ivo exp os u res
t o D -S H E ma A y b e p o s i t i v e l y a s s o d c i with a t e NKC A le vel s at Ti me 0 p oin t.
3 .3 .4.2 En d ogen ou s h o r m o n e s levels an d t h e i n c as r e ed level s o f N K C A a f t e r ho u 2 r 4 s i n v i t r o
i n c ub a t ion o f P B M C s w i t h o u t e x o g e n o u s c o r t i s o l
T h e res u l t s fro m p re vi ou s e x p e r i m e n t [ 3 . 3 . 4 ] s h owed th at th ere were in d ivid u al
d i f f e r e n c e s
i n t h e l afte e v r 2 e 4 l h o s u r s o i f n c u b N a w t K i t i C h o A u n t e x o g e n o u s c o r t i s o l, i. e.
s o m e o h f a d h i g t h h l e v e of l m s N KC A a n d th e ot h ers h a d l o w l e v e . l In s d ivi d u al s were d ivi d ed
in to th ree g rou p s (h igh , mi d d le an d low NKC A l evels ) acco rd in g to a v e r a g e d l e v e l N at s K C A
th e rati o of 5 0 :1 an d 2 5 :1 a f t e r 2 4 h o u r s i n w c u i t b h a o t u t i c o n r t is o l [Fi gu re 64].
NKCA a f t e r 24h r s i n c u b a t i o n
45
30
15
0
G r o u p o f i n d i v i d u a l s w i t h h i g h l
(H i g h N : K me C aA n = 3 4 .2, SD = 6.8, n = 11)
G r o u p o f i n d i v i d u a l s w i t h m i d d l
(M i d N K : me C A an = 20.6, SD = 3.3, n = 9)
Gr oup of i ndi vi dual s wi t h l ow l e v e l s o f t h e N K C A
(L o w N K : C me A an = 7.1, SD = 4.8, n = 11)
Fi gur e 64: G r o u p s d e f i n e d b y t e r t i a r y s p l i t o f t h e N K C A l e v e l s a f t e r 2 4 h o u r s i
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 46 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Th e g r o u p ith o f h i g h p l e o v e p l l s e o f t w h e t h N e t K e r C t A i a r y i s n p l i t High s ( N KC A:
m e a n = 4.2, 3 SD = 6.8, n = 1) 1 1 an / 3 d t h e g r o u p o f p l e p w e o h o h a v e l o w l e v e l Low s ( N KC A:
m e a n = 7 . 1, SD = 4 .8, n = 1) 1 1 were / 3 co mp ared wi th reg ard to th e levels of th eir en d ogen ou s
h orm on es b y i n d e p e n d e t n t-tests. In ad d it ion , co rrel at i on an al ys es wer e p erf or med to ex amin e
th e a s s o c i a t s i b o e t n w e e n e n d o g e n o u s h or mon es lev els an d th e in creas ed levels o f NKC A after
2 4 h ou rs i n cub at i on .
C o r t i s o l l e v e l s
E n d o g e n o u s p l a s m a l e v e l s o f c o r d t i n s o s o i l g n i h f i a c a n t c orrel at i on with th e levels of th e
N K C A b o t h a t t h e r a t i o o f , n 5 0 = : 1 3 1 ( , ) r n s a = n d . 2 0 5 9 : 1 ( , r n = . 3 1 0 , 2 ) n , s a n o d n
statisticall y s ign ifi can t d iffer en ce i n m e a n s b e t w e e n t h e H i g h N K C d A the g Low r o u Np KC a n A
grou p was f ou n d [ Fi gu re 6 5 ].
Mean (95% C.I.) plasma cortisol levels (nM)
2 0 0
1 5 0
1 0 0
5 0
0
Lo w N KCA
i n d i v i d u a l s
M id NK CA
i n d i v i d u a l s
Hi gh NK CA
i n d i v i d u a l s
Fi gur e 65: M ea n (95% C.I .) pla s ma le ve ls of c ort is ol in t he High , int e r me diat e ( M id) a n d Lo w NKC A
l e v e l g r o u p a s f t e r 2 4 h o u r s i n c u b a t i o n
D H E A -S l e v e l s
N o t s nificant
i g
En d ogen ou s p l as ma l evel s of D H E A -S a p p eared to b e p os itivel y as s ociated with N K C A
l e v e l s b o t h a t t h e r (r a t i = o , . n o 3 f = 8 35 1 0 , : p 1 = 0 . 0 ) 3 an 7 d 2 5 :1 (r = , . n 3 = 7 3 1 , p = 0 . 0 ), 3 8
an d th e Hi gh N KC A gr ou p h ad s i gn ifican tl y h i g h e r l e -S v co e mp l s ared wo it f h th e D level H E s A
of th e Lo w N KC A g rou p [F i g u r e 6] (me an d ifferen ce = 1.6, t = 2.1, d f = 2 0 , p = 0 45) . 0 .
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 47 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Mean (95% C.I.) plasma DHEA-S levels (mg/dl)
5
4
3
2
1
0
L ow N KC A
i n d i v i d u a l s
M i d N KC A
i n d i v i d u a l s
Hi g h NK CA
i n d i v i d u a l s
Fi gur e 66: M ea n (95% C.I .) pla s ma le ve ls of D H E A -S in t he High , in t e r me diat e ( M id) a n d Lo w NKC A
l e v e l roups g a f t e r 2 4 h o u r s i n c u b a t i o n
M e l a t o n i n l e v e l s
En d ogen ou s p las ma level s of m e l a t o n ap i n p eared to b e p o s i t i v e l y a s s o c iated with N K C A
l e v e l s b o t h a t t h e r (r a t = i .4 o 2 , n o f = 35 1 0 , : p 1 = 0 2 . 0 0 ) an d 2 5 :1 (r = , . n 3 = 8 3 1 , p = 0 . 0 ). 3 8
M o r e o v e r , th e Hi gh N K C A g r o u p h a s d i g n i f i c ha igh n t el r y lev el s of mel at on in co m p ared with
t h e l e v e l os w No KC f A gr t ou h p e [F i L g u r e 6 7] ( m e a n d i f f e r e 5.2, n c e t = 3 .2 1 , d f = 2 0 , p =
0 . 01 0 ).
p = 0 . 0 4 5
I n a d d i t i o n , e n d s o pg las e n ma o u level s of mel at on in s h o w ed s i g n i f i c a ith n t c o r r e l
t h e i n c r e a d s levels e o f th e N KC A a ft er 2 4 h ou rs fro m T i m e 0 t i m e p o i n t a t t h e r a t i 0 : o 1 (r o f 5
= . 4 , n 7 = 3 1 , p = 0 . 0 ) 0 8 a n d 5 : 2 1 ( r , = n = . 34 1 2 , p = 0 . 0 ). 1 9
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 48 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Mean (95% C.I.) plasma melatonin levels (pg/mL)
4 0
3 0
2 0
1 0
0
L ow N KC A
i n d i v i d u a l s
M id N KCA
i n d i v i d u a l s
High N KC A
i n d i v i d u a l s
Fi gur e 67: M ea n (95% C.I .) pla s ma le ve ls o f me la t o n in in th e High , in t e r me d ia te (M id ) a n d Lo w N KC A
le ve l gr o u p s a f t e r 2 4 h o u r s i n c u b a t i o n
C o n c l u s i o n :
Th es e res u lt s s u gges t th at p rior i n v i ex v o p os u re to c ort is ol d id n ot a f f e c t N K C A l e v , e l s
b u t t h a t p r i o r i n v i v e o x p o s u r e -S s a n d t m o e l a D t w H o n e E r i A e n as s oci at ed wi th th e in creas ed
l e v e l s o f NK C A a ft er 2 4 h ou rs i n v i t i r n o c u b a t . i o n
S u m m a r y :
T h e s e r e , s b y u th e l f t l -c s o y t w o m c e t o r n y f a n d i c r o l m o r i m meth e t r od i c s that th e lev el s of
t h e N af K t e C r A in c u b a t i o n o f P B M C s f o r 2 4 h o i u r n s c r e a . s e h d e T r e w e r e ch n an o ges in N K -
c e l l an d c y t o t o -c x e l l i p c er c e n t N a g K e s a f t e r t h e 2 4 h o u r s i n c u b a t i o n o f P B M C s , b u t ht e
e x p r e s s i o n o f Nkp t h e 4 6 recep tor was s h own to in cre as e wh ile th e exp res s ion of t h e Nkp 3 0 was
n o t a f f e c t s i e d g n i f i c . a Th n t e l in y creas e of N KC A levels after 2 4 h ou rs in cu b ation was s h own to
b e a s s o c i ted a wit h th e in creas e in Nkp 4 6 exp res s ion .
p = 0 . 0 3 7
U p p e r p h y s l i o g i c a l l e v e l s o f c no M), r t i in s vi o l tr o ( s t 2 r 5 e 0 s s mod el , we re s h own t o
inhibit t h e in creas e of N KC A s een a f t e r 2 4 h r s i n c . u Th b a e t di egree o n of in h ib it ion in th e NKC A
b y t h e 2 5 0 n M c o r t i s o l w a s a l m o s t t o th e s ame d eg ree of i n cre as e in th e levels of N KC A a fter 2 4
h o u r s i n cu b at i on of P BMC s . T h is in h ib ition in th e NKC A level w a s not as s o ciated with a
n u m e r i c a l c h a n g -c e e l i l n s t h a e n d l -c t e v h l e l l -p s u s o c b p u y l t a o t o f i , t o bn uo t N th x K e i c N K
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 49 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
i n h i b i t i o n s w s a h o w n t o b e a s s o c i a t e d w i t h i n h i b i t i o n ( m o . f . i N . on ) k p c4 yt 6 ot e ox xi p c r e s s i o n
N K -c e l l s u b s e . t Howe s ver, th e d egree o f inhibition o f N k p 4 6 e x p r e ds id s i no ot n f u l l y m a the t c h
s u p p r e s s i o n f t h e i n c r e a s e a f t e r 2 4 h . o u T r h i s s i f n c i u n b d a i t n i g o n i at m p th l ere i e are s ot t h er
con trib u t i n g fact ors ap art f ro m th e N kp 4 6 exp res s ion .
T h e a n a l y s e s i n a s s o c i a t i o n s b e t w e e n e n d o g e n o u s l e v e l s -h o or f ms t on r e es s s (co rt is ol ,
de h y d r o e p i a n d r o s t e r o n e s u l p h a ( t e D H -S E ) A an d mel at on in ) an d NKC A le vels at T ime 0 , i.e .
b e f o r e e t in h cu b at ion of P BMC s , d e m o n s t r a t e d t h a t t h e r e n o w e s r i e g n i f i c a n t r e s. l a t i o n s h i p
H o w e v e r , t h e r e a p p e a r e d een t en do ogen b ou e s level p s o of s D i H E t A -S i an v d e c o r r e l
m e l a t o n , i b un t n ot co rt is ol , a n d t h e N K C A l e v e l s ho u a r f s t o e f ir n vi 2 t4 r o i n c u b at i o , n i.e. aft er
i n c u b a t i o n w i t h o u t t h pe res en ce of e n d o g e n o u s h o r m o n e s. Th es e res u lts s u gges t th at th e level s
of p r i o r i n v i v e o x p o s u r -S e a n t d o m e l D a H t , E o bn uA i t n ot co rt is ol , ma y h ave b een p os itivel y
as s ociat ed wi th th e in creas ed levels o f N KC A a fter 2 4 h o u r s in vit r o i n c u b a t i . Toget o n h er wi th th e fin d i n gs t h at t h e i n creas ed levels of N KC A w ere in h ib ited b y th e p res en ce of u p p er
p h ys i o l o g i c a l l e v e l s o f c o r t i s o l [ 3 . 3 . 1 . 3 a n d 3 . 3 . 3 .4 ] a n d i n t h e t l e i r a t u r e [1 .2 .2 .3 an d 1 .2 .4 .2 ], it
w a s s u g g e s t e d A-S t h a t n d D H m E e l a t o n i n m -c a ells y in vi h vo a as v a e cou na ter f f e c t e d t
regu lat o r y h o rm on e a gai n s t cortis ol in N KC A le vels .
Th es e fi n d i n gs s u pp ort t h e h yp oth es es th at p h ys iol ogi cal le vel s o f c orti s ol can s u pp res s
N K c y t o t o x i c a c t i v i ; t y a d n i d r e c t h l A-S a y t a D n d H E m e l a t o n i n h a m v e a c y o u n t e r a c ting e f f e c ts
again s t cort is ol u p on th e N K c y t o t o x i c a . c Th t i is v con i t cl y u s ion s u p p ort s th e p remis e th at th ere
is a d i r e c t h o r m -i o n m e m u n i t l y i n k a g e a s a n e -im n d o mu c r ni e n arm o of th e p rop os e d in tegrated
p s y c h o-n e u r o-e n d o c r ino-i m m u n e n e t w o rk; an d p artiall y s u p p orts th e h yp oth es i s th at s t res s ma y
h a v e a d e t r i m e n t a l e f f e c . t Th u is p lo ead n s h e o n a tl o t th h e n ext i n v i exp t r o eri men ts exami n in g
t h e e f f e c t o f -l c y m o p r h t o c i y t s e s o l a s a u n p i o n v e s T t i g a t i o n o f a n o t h e r d -i
r e c t h o r m o n e
i m m u n i t y l i n k a g e , i . e . l i n k a g e b e t w t e e h n e c o r t a i d s o a l p a t n d .
i v e i m m u n e s y
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 50 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
3 . 4 In v it ro i n v e s t i g a t i o n i n t o t h e e f x f p e o c s t u r o e f t str e o e ss hor mo ne u p o n T-
l y m p h o c y t e s
B a c k g r o u n d
T-l y m p h o c y t e s a r e i m p o r t a n t c e l l u l a r c o m p o n e n t s o f t h e a s d ys a tem p t i , v an e d i m m u n e
on e of t h e i r m a j o r f s, u pn rolif c t i erat o n i on (an in creas e of th e s p ecific c ell t yp es a ga in s t s p ecific
a n t i g e n s ) [s ee al s o 1 . 2 . 1 ] . is 1 kn own to b e affect ed b y th e s tres s h or mon e, cortis ol.
Ph armacol ogi c al le vel s o f e x o g e n o u s g l u c o c o r t i c o i d are s k n o w n t o s u -l p ymp p r he oc s yt s e T
p roliferat i ve act i vi t y i n v i . t In r t o h i s p r o j e c t , th e e f f e c t s o f p h y s i o l o g i c a l l e v e l s co ortis f ol u p on
T-l ymp h oc yt es we re i n ves t i gated b y as s e s s in g p roliferati ve r es p on s es again s t an tig en s an d a
mito gen . T h e p r o l i f e r a t e i was o n a s s e s s e b d y u s i n g [
3 H ] -t h y m i d i n e i n c o r p o r a t i o , n an d m e t h o d
later t h e e x p r e s s i o n o f v a r i o u s c e l l s u r f a c e r e c b e p y t o r u s s w -c i a yto s n met e g x ra y m tf o i n l e d o w
e x p l o r e t h e -l p r y m o p f h o i c l y t e s -p s u op o b uf lat ion T s .
A i m s
T o c o n f i r m th e s u p p res s i ve e f f e c t o f a ma jor s tres s h o rm on e, c o r t i s o l , u p on T-
l y m p h o c y t e p r o l i f e r a t i v e r e s p , o n s e s a n d t o e x p ech l an o is ms r e at t h e t h e u n d e r
c e l l u l a r l e v e l
W o r k i n g h y p o t h e s i s
“A n in vi tr o m od el of s u s t a i n e s t d r e s s i m p a i rs T-l ymp h o c yt e p r ol ife rative a c t i v .” i t y
In vitr o mod el o f s u s t a i n se tres d s is d efi ned as “mo re th an 2 4 h ou rs of e xp os u re t o u p p er
p h ys i o l o g i c a l l e v e l s o f c o r t i s o l”.
3 . 4 . 1
T-l y m p h o c y t e p r o l i f e r a t i v e r e s p o n s e s a g a i n s t c o m m o n a n t i g e n s
T h i s s e r i e s o f e x p e r i m e n ts was d es ign ed to c o n f th e i s ur p p res m s ive e f f ect of c ortis ol u p on
T-l ym p h o c yt e p r o l i f e r a t io n , a n d t o e x p l o r e t h e e f f e c t o f c o r t i s o l a t u p p e r p h y s i o . l o g i c a l l e v e l s
Wh en p e r i p h e r a l b l o o d m o n o n u c l e a r c e l l P s B ( M C s ) a r e i n c u b a t e d p reviou w i t sh l y
en cou n tered an ti gen s , mem or y T-l y m p h o c y t es a r e s t i m u l da ivid t e d le t ad o in g to i n creas ed
3
i n c o r p o r a t i o n o f [ H ] -th ym id in e. Un d er th e cu ltu re con d ition s u s ed , s u ch cu ltu res s h ou ld give
rad ioact i ve cou n t s i n exces s of 3,0 0 0 cou n ts p er min u te (cp m).
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 51 - I m p e r i a l o C n o d l o n l e g e L

Individual 3 H-thymidine incorporation per PBMCs culture well (cpm)
P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
40 00
30 00
20 00
10 00
0
P BMC s fro m ten h e a l t h y s u b j e c t s w e r e i n c u b a t e d w i t h o r n w s i (p t uh ri o fi u ed t a n t i g e
p r o t e i n d e r i v a t i v e ( P P D ) o r H e r p e s z o s t e r a n t i g in e n va ) ri ou s con cen trat i on s of cort is ol (0 , 2 5 ,
2 5 0 and 2 50 0n M). Al l d at a wer e coll ecte d on th e 6 t h d a y o f i n c u b , a an t i d o pn rol ife rat ive res p on s es were me as u red b y th e [ 3 H ] -t h y m i d i n e i n c o r p o r a t io n m e t h . o d
3 . 4 . 1 T-l ym p h o c yt e p r o l i f e r a t i o n a f t e r i n c u b a tion of P BMC s fo r s ix d a ys with a n d with ou t
e x o g e n o u s c o r t i s o l
As e xp ect ed , i n vi t r o i n cu b at ion of p erip h eral b lood mon on u clear cell s (P BMC s ) in ti s s u e
c u l t u r e m e d i u m ( T C M ) a l o n e f o r s i x d a did y s n ot cau s e l ym p h o c yt e p r o l i f e r a t ive re s p on s es
[Fi gu re 6 8 a , ]. b N ot s u r p r i s i n g l y, th e a d d i t i o n o f v a r i o u s a m o u n t s o f c o r t i s o l (u p p er
p h y s i o l o g i c a l l e v e l s : 2 5 0 n M , 2 5 n M a n d 2 5 0 0 n M h a ) d n o e f f e c t h i s u p r e o s n u l t.
6 d a y c u l t u r e wi t h o u t a n t i g e n
Mean of 3 H-thymidine incorporation per PBMCs culture well (cpm)
0 n M 2 5 n M 2 5 0 n M2 5 0 0 n M
5000
4000
3000
2000
1000
0
N =
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 52 - I m p e r i a l o C n o d l o n l e g e L
1 0
1 0
�� ����� ��� � � � � � ������ �
1 0
0 n M 2 5 n 2 M 5 0 2 n 5 M 0 0 n M
Fi gur e 68a : i n d i v i d u a l b a c k g r o u n d p s r of o l i f e Fi r gu a t r e i 68b: o n me a n ba c kgr ou nd pr olif er at io n
P B M C s c u l t u r e d w i t h o u t a n t i g e n o f P B M C s c u l t u r e d w i t h o u t a n t i g e n
1 0

Individual 3 H-thymidine incorporation per PBMCs culture well (cpm)
P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
3 . 4 . 1 2 T-l ymp h oc yt e p r ol ife rat ive res p on s e ag ain s t p u r i f i e d p r o t e i n d e r i v a t i v PPD) e ( a f t r e
3 00 00
2 50 00
2 00 00
1 50 00
1 00 00
50 00
0
i n c u b a t i o n o f P B M C s f o r s i x d a ys w i t h o r w i t h o u t e x o g e n o u s c o r t i s o l
P BMC s fro m n i n e v o l u n t e e r s o u t o f r e t s p e o n d e d s a t i s f a c t o ily r to in vi tr o s ti mu lat ion with m yc ob act eri u m an t i g en (p u rified p rotein d erivati ve : P P D). Figu r e 6 9 a s h ows th e in d ivid u al
r es p o n s e s f ro m n i n e vol u n teers wh os e P BMC s r e s p o n d e d s a t i s f a c t o ily r t o in vi tr o s ti mu lat ion with t h e a P n t P i D g an e n d th at al l res p on s es b u t on e were red u ced b y th e ad d ition o f 2 5 0 n M
c o r t i s o l a n d a l l r e s p o n s e s w e r e s u p p r e s s e d b y t h e a l. d d Th i e t ad i o dn it ion o f of 2 5 0 0 n M c o r t i s o
c o r t i s o l i n d u c e d a -d e d p o e s n e d e n t d e c r e a s t h e e i a m n o u n t o f [ 3 H ] -t h i d y i n m e i n c o r p o r a te d (F =
3 4 .95 , p < 0 . 0 0 1 ) [Fi gu re 6 9 b ] . Pai red t-t es ts s h owed s ign ifican t r e d u c t i s o f n r 0o n M m to 2 5 0 n M
(t = 8 6 0 4 , p = 0 .0 0 1 ), an d f r 0o n M m to 2 5 0 0 n M (t = 1 2 0 1 7 , p = 0 . 0 0 1 )
I n d i v i d u a l p r o l i f e r a t i o n r e s p o n 20000 s e t o P D
0 n M 2 5 n M 2 5 0 n M 2 5 0 0 n M
Lymphocyte proliferative responses to PPD
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 53 - I m p e r i a l o C n o d l o n l e g e L
15000
10000
5000
0
- 5000
N =
9
No dr ug
9
2 5 n M
9
9
2 5 0 n M
2500nM cortisol
Fi gu r e 69a : individua l pr olif e r at io n re s po nse Fi gu r e 69b: Me a n ( 9 5 % C . I . pr ) olif er at io n
of P BM Cs t o the PP D a nt ige n r e s p o n s es o f P B M C s t o t h e P P D a n t i g e n
C o n c l u s i o n :
Ex o g e n o u s c o r t is ol s u p p r e s se s -d P ep P en D d en t T-l ymp h o c yt e p r olife rative res p on s es , an d
th is can b e s een at t h e u pp er p h ys iol ogica l levels of c ortis ol , 2 5 0 n M as well as 1 0 times h igh er
(2 5 0 0n M).
p = 0 . 0 0 1
p = 0 . 0 0 1

Mean 3 H-thymidine incorporation per PBMCs culture well (cpm)
P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
3 . 4 . 1 3 T-l ymp h oc yt e p r ol ife rat ive res p on s e ag ain s t Herp es an tigen a f t e r b i a n t ion c u of P BMC s
for s ix d a ys wi t h a n d w i t h o u t e x o g e n o u s c o r t i s o l
S i m i l a r f i n d i n g t s o t h o s w e r e w o i b t a wh i h n en e d P a Herp P D es z os ter an ti gen w as u s ed .
P BMC s fro m ten v o l u n t e e r s e s p o n d e d s a t i s f a c t o ily r to in vi tr o s t i m u l a t i o n H w e i r p t e h s a n t . i g e n
Fi gu re 7 0 a s h ows i n d i v i d u a l r e s p o n s from e s ten v o l u n t e e . r s All res p on s es b u t on e were red u ced
b y t h e a d d i t i o n o f c o r t i s o l. Th e a d d i t i o n o f c o r t i s o l i n d u -d c e ep d en a d en d o t s de ecreas e in p roliferat i ve res p on s es meas u red b y [ 3 H ] -th ymid in e in corp orati on ( F = 1 5 .9 6 , p = 0 . 0 0 2 )
[Fi gu re 7 0 b ] . P os t h oc p ai red t-tes t s h ow ed s ign ifican t r e d u c t i s o f n r 0o n M m to 2 5 0 n M (t = 9 5 7 8 ,
p = 0 .0 0 4 ), an d f r 0o n M m t o 2 5 0 0 n M (t = 1 5 3 86 , p = 0 .0 0 1 ).
800 00
700 00
600 00
500 00
400 00
300 00
200 00
100 00
0
I ndi vi dual prol ife rat io n re s pons e to He rpe s
Lymp hocyte proliferative resp on ses to Herp es
0 n M 2 5 n M 2 5 0 n M2 5 0 0 n M
60 000
50 000
40 000
30 000
20 000
10 000
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 54 - I m p e r i a l o C n o d l o n l e g e L
0
N =
1 0
No dr ug
1 0
2 5 n M
1 0
1 0
2 5 0 n M
2500nM cortisol
Fi gu r e 70a : i n d i v i d u a l p r o l i f e r a t i p o n s e r e o s f Fi gur e 70b: M e a n ( 9 5 % C . I . pr ) olif er at io n
P BM Cs t o Her pes a nt ige n r e s p o n s es o f P B M C s t o H e r p e s a n t i g e n
C o n c l u s i o n :
Exo gen ou s co rt i s ol s u p p r e s se s T-l ymp h o c yte p roli ferati ve res p on s es to m em or y a n tigen s ,
a n d t h i s c a n b e s e e n a t t h l e o g i u c p a p l e l e r v e l p s h o y f s c i o o r t i s o l, 2 5 0 n M as well as 1 0 times
h i g h e r (2 5 0 0n M).
p = 0 . 0 0 4
p = 0 . 0 0 1

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
3.4 . 2 T-l y m ph ocy te prol if era tive res pons es a g a ins t s u p e r-a n t i g e n m a n i d t o g e n
Ha vin g s h own t h at t h e ad d i t ion of c o r t i s o l in d u ced a d os e d ep end en t d ecreas e in i n v i t r o
a n t i g e n s p e c i f ic -l T y m p h o c y t e p r o l i f e r a t i v e r e s p o n s e s s, eries t h i of s e x p e r i m e n t s was d es ign ed
to d etermi n e i f c on cu rren t exp os u re t o c o rtis ol (2 5 0 n M) h a d s i m i l a r e f f e c t s in vitr f o l o l o w i n g
s t i m u l a t i o n p o w i e r t f u h l p a n -c e T l l s t i m nt u s l , a i . e . s u p -an e r tigen - s t a p h y l o c o cal c en terot o xi n
B ( S E B ) an d mi t ogen - p h y t o h a e m a g g l u t i n A i ( P n H A ).
Th e n u mb er of c el l s p art i cu l arl y in th e p r oliferati ve res p on s e to th es e SE B an d P HA i s
g r e a t e r a n d t h e m a x i m u m r e s p o n s e o c c u r s e a r l i e r t h a n f o r m e m o r y r e . c T a l h l e s e a n t i g e n s
res p on s es s h o ul d gi ve rad ioacti ve c ou n ts in exces s of 1 0 , 0 0 0 c o u n t s p e r m i n u t e ( c p m on ) Da y 3
o f c u l t u . r With e th es e m ore p owerfu l s ti mu li, th e as s a y was m od ified to u s e a wh ole b lo od
meth od rat h er t h an P BMC s wh ich are ti m e con s u min g to p rep are.
Blo od fr om t w e l v e h e a l th y s u b j e c t s w e r e , o d n i e l i u n t f e o d u , r w i th TC M an d in cu bat ed
for t h r e e d a y s with a n d wi t h ou t SEB a n d P H A, in th e p res en ce or ab s en ce of 2 5 0 n M co rti s ol .
All d at a were col l ect ed on t h e third d a y o f in cu b ation .
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 55 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
3 .4 .2 . 1 T-l y m p h o c y t e p r o l i f e r a t i v e r e s p o aga n s e in s s t s tap h yl ococ cal en ter oto xin B (SE B) after
i n c u b a t i o n o f d i l u t e d w h o l e b l o o d f o r t h r e e d a ys w i t h o r w i t h o u t e x o g e n o u s c o r t i s o l
Lym p h oc yt es in th e d il u ted wh ole b lood s amp les fro m t w e l v e v o l u n t e e r rs es p on d ed
s a t i s f a c t o rily to in vi tr o s t i m u l a t i o n w i th s t a p h y l o c o c c a (S l E B) e [Fi n g ut re e 71a]. r o t Th o e x i n B
ad d ition of 2 5 0 cortis n M ol in d u ced a d e c r e a s ed res p on s e (mean d if feren ce = 1 8 2 35 , SD = 8 6 7 2 ,
t = 7 .3, d f = 1 1 , p < 0 . 0 ) 0 [F 1 i g u r e 1b]. 7
Individual proliferative responses to SEB (cpm)
Lympho cyt e s prol i f e ra t i ve re s pon s e s
1 2 0 0 0 0
t o S EB
1 0 0 0 0 0
8 0 0 0 0
6 0 0 0 0
4 0 0 0 0
2 0 0 0 0
0
No dr ug Cort isol
P ro liferativ e resp o n ses to S E B (9 5 % C . I.)
10 0000
7 5000
5 0000
2 5000
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 56 - I m p e r i a l o C n o d l o n l e g e L
0
N =
1 2
No dr u g
Fi gu r e 71a : I nd i vi d u a l p r o l i f e r a t i v e Fi gur e 71b: M e a n ( 9 5 % C . I . ) p r o l i f e r a t i v e
r e s p o n s e s of P BM Cs t o t h e S E B r e s p o n s e s o f P B M C s to th e SEB
w i t h / o ut co r t i s o l a t Da y 3 w i t h / o ut co r t i s o l a t Da y 3
C o n c l u s i o n :
U p p e r p h y s i o l o g i c a l l e v e 2 l ( 5 0 ) o n f c o M r t i s o l c a n d e c r e a s e p r o l i f e r a ti v e r e s p o -n
s e s o f T
l y m p h o c y t e s a g a i n s t a s u p -an e r tigen , S E B.
Mean (95% C.I.) proliferative responses to SEB (cpm)
p < 0 . 0 0 1
1 2
Cortisol

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
3 .4 .2 . 2 T-l y m p h o c y t e p r o l i f e r a t i v e r e s p o n s e s a g a i n s t p h A (P y t HA) o h a e aft m ea r g g l u t i n i n
i n c u b a t i o n o f d i l u t e d w h o l e b l o o d f o r t h r e e d a ys w i t h o r w i t h o u t e x o g e n o u s c o r t i s o l
L y m p h o c y t e s i n ilu t ted h e wh d ol e b lood s amp les fro m t w e l v e v o l u n t e e r rs es p on d ed
s a t i s f a c t o rily to in vi tr o s t i m u l a t i o n p h w y t i o h t a h e m a g g l u t i n i n A ( P H A [Fi ) gu re 72a a n d b ]. Th e
ad d ition of 2 5 0 cortis n M ol in d u ced a d e c r e a s ed r e s p o n s (mean e d if feren ce = 7 4 5 14 , SD =
2 2 85 6 , t = 1 .3 1 , d f = 1 1 , p < 0 .0 0 1 ).
Individual proliferative responses to PHA (cpm)
Ly mph o cy t e s prol i f e ra t i ve re s po n s e s
2 5 0 0 0 0
t o P H A
2 0 0 0 0 0
1 5 0 0 0 0
1 0 0 0 0 0
5 0 0 0 0
0
No dr ug Cort isol
P roliferative responses to P H A (95% C . I.)
200000
150000
100000
50000
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 57 - I m p e r i a l o C n o d l o n l e g e L
0
N =
1 2
No dr ug
Fi gur e 72a : I nd i vi d u a l p r o l i f e r a t i v e
Fi gur e 72b: M e a n ( 9 5 % C . I . ) p r o l i f e r a t i v e
r e s p o n s e s of P BM Cs t o t he P H A r e s p o n s e s o f P B M C s to the P H A
w i t h / o ut co r t i s o l a t Da y 3 w i t h / o ut co r t i s o l a t D y a 3
C o n c l u s i o n :
1 2
Cortisol
T-l ymp h oc yt e p r ol i fe rat i ve res p on s es to i n vitr o s timu lati on with a s u p e r -an tigen a n d a
m i t o g e w n e r e s u p p r e s s e d b y t h e a d d i t i o n co ortis f ol ( 2 5 0 n M ) .
p < 0 . 0 0 1

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
3.4 . 3 C e l l s u r f a c e m a r n k p e r o s l i f e o r a t ing T-l y m p h o c y t es foll ow ing s timula tion w ith
P HA
H a v i n g s h o w n t h a t 2 5 0 n M c o r t i s o -l l y m d p h e o c y r t e a p s r o e l d i f e T r a t i v e r s e s p o n s e
again s t a mi t ogen , a s e r i o u s o f i n v e s w t a i s g a p t e i r o f n o r m t o e id d en ti f y th e u n d erl yi n g
m e c h a n i s m s f o r t h i s s u p p r e s s i v e e f f e c t o f oc yte c o p r rt ol i iferat s o l i on u . p o n l y m p h
3 .4 .3 . 1 E x p r e s s i o n o f a n a p o p t o s i s ( C D 9 5 : -l ymp F a h oc s yt ) es i c n e l v i l t r s o u r f a c e m
d u rin g P H A-i n d u c e d p r o l i f e with r a t a i n o d n w i t h o u t e x o g e n o u s c o r t i s o l
T h i s e x p e r i m e n t e x a d m th i n e e exp res s i on of C D9 5 / Fas wh ich is a ma rke r o f ap op t os is on
T-l y m p h o c ytes d u ri n g P H A-in d u ced p roliferativ e res p on s es . Dilu ted wh ole b lo od fro m s ev en
h e a l t h y s u b j e c t s w e r a n a l y s e b d y f l o w c y t o m at e t r i m y e p o i n o t f s 0 , 2 4 , an d 4 8 hou rs of
i n c u b a t i o n a f t e r s t i . m Tu h e l e x a p r t e s s i o n o o n f C D 9 w 5 i -FI t T C h f l u o P r e H s c A e n t c o n j u g a ted
a n t i b o y d o n e a c l h y m p h o c y t e s u -p b op u lat ion s u rface was meas u red b y fl ow c yt om etr y.
I n u -s n timu lat ed b lood cu lt u res , th e exp re s s ion of C D9 5 / Fas , ap o p t o s i s m a r k e r, b y C D4
a n d C D -cells 8 T was u n al tered ove r th e 4 8 h ou rs p eriod [Figu re 73a / b a n d F i g 4a/b]. u r e 7
Individual percentages of CD8 T-cells
expressing CD95 (%)
80
60
40
20
0
Mean (95% C.I.) CD95 expression (%) on CD8 T-cells
8 0
6 0
4 0
2 0
0
T i m e 0 b a c k g 2 r 4 o h u r n d s b a c k g r o 4 u 8 n h d r s b a c k g r o u n d
0h 24h 48h
Fi gur e 73a : I ndividua l ba c kgr ou nd p e r c e nt a g e s Fi gu r e 73b: M e a n ( 9 5 % C . a I c . kground ) b
o f C D -c 8 e l T l s e x p r e s s i n g C D 9 5 p e r c e n t a g e s o f C D 8 -c e T l l s e x p r e s s i n g C D 9 5
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 58 - I m p e r i a l o C n o d l o n l e g e L

Individual percentages of CD8 T-cells
expressing CD95 (%)
P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Individual percentages of CD4 T-cells
expressing CD95 (%)
80
60
40
20
0
Mean (95% C.I.) CD95 expression on CD4 T-cells
8 0
6 0
4 0
2 0
0
0h 24h 48h T i m e 0 2 4 h r s 4 8 h r s
Fi gur e 74a : I ndividua l ba c kgr ou nd p e r c e nt a g e s Fi gu r e 74b: M e a n ( 9 5 % C . a I c . kground ) b
o f C D -c 4 e l T l s e x p r e s s i n g C D 9 5 p e r c e n t a g e s o f CD4 T-c e l l s e x p r e s s i n g C D 9 5
Wh en b lo od was s ti mu lat ed with P HA, i n c r e a si n g p e r c e n t a g e s o f -cells C D 4 a n d C D 8 T
e x p r e s se d t h Ce D9 5 marker at 2 4 a n d 4 8 h ou rs i n c u b a t i [Figu o n re 75a a n d F i g u 6a r e ] . 7 T e h
in creas es at 4 8 h ou rs were s tatis ticall y s i gn ifican t [ F i g u r e 7 5 b a n d F i b g ] u . r e 7 6
80
60
40
20
0
0h 24h 48h
Mean (95% C.I.) CD95 expression (%) on CD8 T-cells
8 0
7 0
6 0
5 0
4 0
3 0
2 0
1 0
N o t s i g n i f i c a n t
T im e 0 wi th PH A
n o c o r t is o l
p < 0 . 0 0 1
p = 0 . 0 0 3
2 4h rs wi t h P HA n o 4 8h rs wi th PHA n o
c o r t i s o l c o r t is o l
Fi gur e 75a : I n d i v i d u a l p e r c e n t a g e s o f C D Fi 8 gu r e 75b: M e a n ( 9 5 % C . I . ) p e r c e n t a g e s o f C D 8
T-c e l l s e x p r e s t i m n u l g a t e C d D 9 5 T-c i e l n l s P e H x A p r e s s i n H g A C s D t 9 i 5 m u i l a n t e P d
whole blood culture in t h e ab s en c e o f c o r t i s o l whole blood culture in t h e ab s en c e o f c o r t i s o l
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 59 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Individual percentages of CD4 T-cells
expressing CD95 (%)
8 0
6 0
4 0
2 0
0
0 h 2 4 h 4 8 h Ti me 0 wit h PHA
n o c o r ti so l
Mean (95% C.I.) expression of CD95 (%) on CD4 T-cells
8 0
6 0
4 0
2 0
0
2 4 h r s wi th PH A n o 4 8 h r s wit h PHA n o
co r ti so l c o r ti s o l
Fi gur e 76a : I n d i v i d u a l p e r c e n t a g e s o f C D Fi 4 gu r e 76b: M e a n ( 9 5 % C . I . ) p e r c e n t a g e s o f C D 4
T-c e l l s e x p r e s t i m n u l g a t e C d D 9 5 T-cel i n l P s H A e x p r e s s t i n m g u l a t C e D d 9 5 i n P H
whole blood culture in t h e ab s en c e o f c o r t i s o l whole blood culture in t h e ab s en c e o f c o r t i s o l
C o n c l u s i o n :
Th e s ti mu lat ion b y P HA l e a d s t o p r o g r e s s i v e l y C D9 i n 5 c r exp e a res s i sn ion g on b ot h C D4
a n d C D -c 8 e l l T s t 2a 4 h ou rs an d 4 8 h ou rs in cu b ation .
N o t s i g n i f i c a n t
p < 0 . 0 0 1
p = 0 . 0 0 1
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 60 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Ad d ition of co rt i s ol i n t h e cu ltu re with P HA h ad little or n o ef fect u p on th e p ercen tage of
b oth C D4 an d C D8 T-cel l s exp res s in g C D9 5 [ Figu re 7 7 an d Figu re 78].
Individual percentages of CD8 T-cells
expressing CD95 (%)
Individual percentages of CD4 T-cells
expressing CD95 (%)
80
60
40
20
0
0h 24h 48h T ime 0 wit h P HA ,
c o r t i s o l
Mean (95% C.I.) CD95 expression (%) on CD8 T-cells
8 0
6 0
4 0
2 0
0
2 4h rs w ith PH A ,
c o r t i s o l
48 hrs wit h P HA ,
c o r t i s o l
Fi gur e 77a : I n d i v i d u a l p e r c e n t a g e s o f C D Fi 8 gu r e 77b: M e a n ( 9 5 % C . I . ) p e r c e n t a g e s o f C D 8
T-c e l l s e x p r e s t i m n u l g a t e C d D 9 5 T-c i e n l l P s H A e x p r e s t i m n u l g a t e C d D 9 5 i n P
whole blood culture in t h e pr e se n ce of c or t i sol whole blood culture in t h e pr e se n ce of c or t i sol
80
60
40
20
0
0h 24h 48h Time 0 with PHA,
cortisol
Mean (95% C.I.) CD95 expression (%) on CD4 T-cells
80
60
40
20
0
p = 0 . 0 5 3
N o t s i g n i f i c a n t
24hrs with PHA,
cortisol
p = 0 . 0 0 1
p = 0 . 0 0 3
p < 0 . 0 0 1
p = 0 . 0 0 1
48hrs with PHA,
cortisol
Fi gur e 78a : I n d i v i d u a l p e rc e n t a g e s o f C D 4 Fi gu r e 78b: M e a n ( 9 5 % C . I . ) p e r c e n t a g e s o f C D 4
T-c e l l s e x p r e s t i m n u l g a t e C d D 9 5 T-c i e n l l P s H A e x p r e s t i m n u l g a t e C d D 9 5 i n P
whole blood culture in t h e pr e se n ce of c or t i sol whole blood culture in t h e pr e se n ce of c or t i sol
C o l l e c t i vel y, t h es e res u l t s s h owed th at th e ad d ition of c ort is ol d id n ot alter th e
p e r c e n t a g es o f t h e c e l e l x s p r e s s in g C 95 D s u r f a c e m a r k Ce r D8 s T-lymp o n h o c yt e [ F i g u r e ] 7 9
a n d C D -l 4 y m T p h o c y t e s [F i g u r e ] 8 at 0 2 4 ( a ) o r 4 ( b 8 ) h o u r s o f i n c u . b a t i o n
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 61 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Mean (95% C.I.) CD95 expression (%) on CD8 T-cells
8 0
6 0
4 0
2 0
0
2 4 h r s w it h P H A n o C o r t is o l 2 4 h r s w it h P H A + C o r t i so l
Mean (95% C.I.) CD95 expression (%) on CD8 T-cells
8 0
6 0
4 0
2 0
0
4 8 h r s wi t h PH A no C o r t i s o l 4 8 h r s w i t h PH A + C o r t i s o l
Fi gur e 79a: M e a n ( 9 5 % C . I . ) p e r c e n t a g e s o f Fi gu r e 79b: M ea n ( 95% C. I. ) pe rc e nt a ge s of
P H A s t i m u l a t -c e d l l s C D e 8 x p r T e s s i n g C D 9 P5 HA s t imula t ed C D 8 T-c e l l s e xp r es s in g CD9 5
a f t e r 2 4 h ou r s o f i nc u b at i o n wi t h / o ut co r t i s o l a f t e r 4 8 h ou r s o f i nc u b at i o n wi t h / o ut co r t isol
Mean (95% C.I.) CD95 expression on CD4 T-cells
80
60
40
20
0
2 4 hr s w i t h PH A n o C o r t i s o l 2 4 hr s w i t h P H A + C o r t i s o l
Mean (95% C.I.) CD95 expression (%) on CD4 T-cells
8 0
6 0
4 0
2 0
0
4 8 h r s w i t h P H A n o C o r t i s o l 4 8 h r s w i t h P H A + Co r t i s o l
Fi gur e 80a : M e a n ( 9 5 % C . I . ) p e r c e n t a g e s o f Fi gu r e 80b: M ea n ( 95% C. I. ) pe rc e nt a ge s of
P H A s t i m u l a t -c e d l l s C D e 4 x p r T e s s i n g C D 9 P5 HA s t imula t ed C D 4 T-c e l l s e x p r e s s i n g C D 9 5
a f t e r 2 4 h ou r s o f i nc u b at i o n wi t h / o ut co r t i s o l a f t e r 4 8 h o u r s b at o f i o n i wi n c t h u / o ut co r t i s o l
C o n c l u s i o n :
C o r t i s o l (-)
C o r t i s o l (-)
C o r t i s o ) l ( +
C o r t i s o l ( + )
C o r t i s o l (-)
C o r t i s o l (-)
C o r t i s o l ( + )
C o r t i s o l ( + )
Up p er p h ys i ol o gi cal l evel s of cortis ol d id n ot alter th e e xp res s ion of the C D9 5 , th e
ap op tos is s u r f a c e m a r k e r, on P HA s timu l ated p roliferatin g T-l ym p h o c y t e s -p u o b p u l a t n i s . o
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 62 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
3 . 4 . 3 . E 2 x p r e s s i o n o f c e l l-s u r f a c e An n e x i n-V an d c y t o p l a s m i P c r o p i d i u m i o d i n e ( P in I ) T-
l ym p h o c yt e s a f t e r i n c u b a t i o n w i t h P HA f o r t h r e e d a ys w i t h o r w i t h o u t c o r t i s o l
H a v i n g s h o w n t h a t c o r t i s o l d i d n o t a f f e c t t h e p e r c e n t a g e s o f c e l l s e x p r e
ap op tos is m a r k e r , t h exp i s eri m en t was p e r f o r m e d t o in ves tigat e actu al ap op totic ch an ges o f
P HA s ti mu lat ed p r o l i f e r a t i n g T-l y m p h o c y t s. e P e r i p h e r a l b l o o d m o n o n u c l e a r c e l l s ( P B M C s )
fro m ten s u b j e c t s w e a r n e a l y s e at d 4 8 h o u rs of in cu b at ion b y f l o w c y t o m ue st in r g y A n n e x i n-V-
FITC f l u o r e s c e n t c o n j u g t i a b t o d e y d a n a d n p r o p i d i u m i o d i n e ( P I) to g a t e a n d m e t a o s u r e t h e
ap op tot ic ch an ges on C D 8 a n d C -l D y 4 m p h T o c y t e s u -p b o p u l a t i s. o Ap n op tot i c cel ls were
d e f i n e d a s c e l l s w i -V-FITC t h A n n pe ox s i it n ive (i .e . cel l s u rf ace h as ch an ged ) an d P I n egativ e
( i . e . c e l l h a s n o t b een col lap s ed or n ecros i s ) s t a i n i in n g flow c yt o met r y.
Th ere was n o s i gn ifi can t d ifferen ce in th e p e r c e n t a g e s o f a p o p t c o e t l l i s c (A n n e x i n-V
p os itive an d P I n egat i ve) b etween P HA s t imu lated P BMC s in cu b ated with an d with ou t 2 5 0n M
cortis ol b ot h on C D 3 + C D 8 + cells [C D 8 -l T ym p h o c yt e : Fi gu re 81a] a n d C D 3 + C D 8 - cells (C D 4 -T
l y p h m o c y t e) [ Fi gu re 81b] .
C o n c l u s i o n :
An n e x i n V ( + ) % i n
CD3CD8 ce l l s
1 0 8 0
6 0
4 0
2 0
0
No d r u gCortisol
An n e x i n V( + ) % i n
CD3+CD8- cel l
1 0 0
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 63 - I m p e r i a l o C n o d l o n l e g e L
8 0
6 0
4 0
2 0
0
No dr ugCort isol
Fi gu r e 81a : I n d i v i d u a l p e r c e n t a g e s o f Fi gur e 81b: I ndivid ua l pe rc e nt a ge s of
a p o p t o t i c C D 8 -c T e l l s incubated 3 days a po pt ot ic C D 4 T-c e l l s i n c u b a t e d 3 d a y s
w i t h a n d wi t h o ut c or t i s o l w i t h a n d wi t h o ut c or t i s o l
Up p er p h ys i ol o gi cal l evel s of cortis ol d id n ot alter th e rate of ap op tos is o f P HA
s timu lat ed T-l ym p h o c y t e s.

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
3 . 4 . 3 . E 3 x p r e s s i o n o f a n a c t -2 i r v e c a e p t i o r o ) n c e l ( l C D s 2 u r 5 f : a c r e I m b L a -r
y k e T
l y m p h o c y t e s d u r i n g PH A -i n d u ced p rol iferat ion with a n d w i t h o u t e x o g e n o u s c o r t i s o l
T h is e x p e r i m e n t e x a m d i th n e e x p r e s s i o n o f t h -cell e a T c t i v a t i o n s u r f a c e m a r k e , r C D2 5 :
I L-2 rec ep tor, o n -l T y m p h o c y t s e f o l l o w i n g s t i m u l a t i o n o f w h o l e b l o o d d w the i t effect h P H A ; a n
of 2 5 0 n M c o r t i s n o l t h i o s e x p r . e s s i o n
Di l u t e d w h o l e d b l f o o r o m s e v e n a h s e s a t i l m t u l h a t y e d s w i u t b h j P e H A c t a n s d a n w a l y s e d
b y f l o w c y t o m at e tim t r e y p oi n ts of 0 , 2 4 , an d 4 8 h o u r s o f i n c u . b Th a t e i e x o p n r e s s i o n o f C D 25-
F I T C f l u o r e s c e n t c o n t j e u d g a a n t i y b o b d y e a c h l y m p h o c y t e s u -p b op u lat ion was me as u red at
e a c h t i m e p o i n t.
I n u -s n t i m u l a t e d b l o o d c u l t u r e s , -2 recep t h e to r, e b x y p C D4 r e an s d s Ci D8 o n o f C D 2 5 ,
T-c e l l s w a s u n a lt e r e d o v e r t h e 4 8 h o u r s p e r i o d 2 [ a F n i d g u F r i e g u 8 3]. r e 8
Individual percentages of
CD8 T-cells expressing CD25 (%)
6 0
4 0
2 0
0
Mean (95% C.I.) CD25 expression (%) on CD8 T-cells
6 0
4 0
2 0
0
0 h 2 4 h 4 8 h T i m e 0 b a c k g 2 r 4 o h u r n d s b a c k g r o 4 u 8 n h d r s b a c k g r o u n d
Fi gur e 82a : I ndividua l ba c kgr ou nd p e r c e nt a g e s Fi gu r e 82b: M e a n ( 9 5 % C . a I c . kground ) b
Of C D 8 -c e l T l s e x p r e s s i n g C D 2 5 p e r c e n t a g e s o f C D 8 -c e T l l s e x p r e s s i n g C D 2 5
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 64 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Individual percentages of
CD4 T-cells expressing CD25 (%)
6 0
4 0
2 0
0
0 h 2 4 h 4 8 h
Mean (95% C.I.) expression of CD25 (%) on CD4 T-cells
6 0
4 0
2 0
0
T i m e 0 2 4 h r s 4 8 h r s
Fi gur e 83a : I ndividua l ba c kgr ou nd p e r c e nt a g e s Fi gu r e 83b: M e a n ( 9 5 % C . a I c . kground ) b
o f C D -cel 4 T l s e x p r e s s i n g C D 2 5 p e r c e n t a g e s o f CD4 T-c e l l s e x p r e s s i n g C D 2 5
Wh en b lo od was s ti mu lat ed with P HA, i n c r e a si n g p e r c e n t a g e s o f -cells C D 4 a n d C D 8 T
e x p r e s se d t h Ce D9 5 marker at 2 4 a n d 4 8 h ou rs i n c u b a t i [Figu o n re 84a a n d F i g u 5a]. r e Th 8 e
i n c r e a s e s a t u rs 4 8 were h o s tat is ti cal l y s i gn ifi can t [ F i g u r e 4b 8 an d Fi gu re 8 5 b ] .
6 0
4 0
2 0
0
0 h 2 4 h 4 8 h
Mean (95% C.I.) CD25 expression (%) on CD8 T-cells
6 0
4 0
2 0
0
p = 0 . 0 0 3
T ime 0 with PH A
n o c o r t i s o l
p = 0 . 0 0 1
p < 0 . 0 0 1
2 4hrs w ith PHA no 4 8hrs w ith PHA no
c o r t i s o l c o r t i s o l
Fi gur e 84a : I n d i v i d u a l p e r c e n t a g e s o f C D Fi 8 gu r e 84b: M e a n ( 9 5 % C . I . ) p e r c e n t a g e s o f C D 8
T-c e l l s e x p r e s t i m n u l g a t e C d D 2 5 T-c i e n l l P s H A e x p r e s t i m n u l g a t e C d D 2 5 i n P
whole blood culture in t h e ab s en c e o f c o r t i s o l whole blood culture in t h e ab s en c e o f c o r t i s o l
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 65 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
6 0
4 0
2 0
0
0 h 2 4 h 4 8 h
Mean (95% C.I.) CD25 expression (%) on CD4 T-cells
6 0
4 0
2 0
0
Ti me 0 w ith PH A
n o c or t i s ol
24 hr s w ith PHA no 4 8hr s w ith PH A no
c or t i s ol c or t i s ol
Fi gur e 85a : I n d i v i d u a l p e r c e n t a g e s o f C D Fi 4 gu r e 85b: M e a n ( 9 5 % C . I . ) p e r c e n t a g e s o f C D 4
T-c e l l s e x p r e s t i m n u l g a t e C d D 2 5 T-c i e l n l s P e x H p A r e s s i 5 n g C i D 2 n s t i P m H u A l a t e d
whole blood culture in t h e ab s en c e o f c o r t i s o l whole blood culture in t h e ab s en c e o f c o r t i s o l
C o n c l u s i o n :
P H A stimulation l e a d s t o p r o g r e s s i v e l y C D2 i n 5 c r exp e a res s i sn ion g on b ot h C D4 a n d
C D 8 -c T ells aft e r 2 4 h ou rs an d 4 8 h o u r s i ation n c u b .
p = 0 . 3
0 0
p = 0 . 0 0 1
p < 0 . 0 0 1
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 66 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
A d d i t i o n o f c o r th t e i cu s o ll tu re t wi o th P HA h ad li ttle or n o ef fect u p on th e p ercen tage of
b oth C D4 an d C D8 T-cel ls exp res s in g C D2 5 [F i g u r e 6 an 8 d Fi gu re 8 7 ].
Individual percentages of CD8 T-cells
expressing CD25 (%)
6 0
4 0
2 0
0
0 h 2 4 h 4 8 h
Mean (95% C.I.) CD25 expression (%) on CD8 T-cells
6 0
4 0
2 0
0
Ti me 0 wi th P H A,
c or t is ol
24 h rs wi th P HA,
c o r t i s o l
4 8 hr s wi th P H A,
c or t is ol
Fi gur e 86a : I n d i v i d u a l p e r c e n t a g e s o f C Fi D gu 8 r e 86b: M e a n ( 9 5 % C . I . ) t a p g e r s c e o n f C D 8
T-c e l l s e x p r e s t i m n u l g a t e C d D 2 5 T-c e i l n l P s H A e x p r e s t i m n u l g a t e C d D 2 5 i n P
whole blood culture in t h e pr e se n ce of c or t i sol whole blood culture in t h e pr e se n ce of c or t i sol
p < 0 . 0 0 1
6 0
4 0
2 0
0
0 h 2 4 h 4 8 h
Mean (95% C.I.) CD25 expression (%) on CD4 T-cells
4 0
3 0
2 0
1 0
0
T ime 0 w i th P HA ,
c o r t is o l
p = 0 . 0 0 5
p = 0 . 0 0 3
p = 0 . 0 0 2
p = 0 . 0 0 1
24hrs w it h PH A ,
c o r t i s o l
p = 0 . 0 0 1
4 8hrs wi t h P H A,
c o r t is o l
Fi gu r e 87a : I n d i v i d u a l p e r c e n t a g e s o f C F D i 4 g ur e 87b: M e a n ( 9 5 % C . I . ) p e r c e n t a g e s o f C D 4
T-c e l l s e x p r e s t i m n u l g a t e C d D 2 5 T-c e i l n l P s H A e x p r e s t i m n u l g a t e C d D 2 5 i n P
whole blood culture in t h e pr e se n ce of c or t i sol whole blood culture in t h e pr e se n ce of c or t i sol
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 67 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
C ollecti vel y, t h es e res u l t s s h owed th at th e ad d ition of c ort is ol d id n ot alter th e
p e r c e n t a g es o f C D [ 8 Figu re 8 8 ] a n d C D [ Figu 4 re 89] T-cells e x p r e s s in g C 25 D s u r f a c e m a r k e r s
at 2 4 ( a ) o r 4 ( b 8 ) h o u r s o f i n c u . b a t i o n
Mean (95% C.I.) CD25 expression (%) on CD8 T-cells
Mean (95% C.I.) CD25 expression (%) on CD4 T-cells
6 0
4 0
2 0
0
6 0
4 0
2 0
2 4 h r s w i t h P H A n o C o r t i s o l 2 4 h r s w i t h P HA + C o r t i s o l
Mean (95% C.I.) CD25 expression (%) on CD8 T-cells
6 0
4 0
2 0
0
4 8 h r s w i t h P H A n o C o rt i s o l 4 8 h r s w i th P H A + C o rt i s o l
Fi gur e 88a : M e a n ( 9 5 % C . I . ) p e r c e n t a g e s o f Fi gu r e 88b: M e a n (95% C. I. ) pe rc e nt a ge s of
P H A s t i m u l a t -c e d l l s C D e 8 x p r T e s s i n g C D 2 P5 HA s t imula t ed C D 8 T-c e l l s e xp r es s in g CD2 5
a f t e r 2 4 h ou r s o f i nc u b at i o n wi t h / o ut co r t i s o l a f t e r 4 8 h ou r s o f i nc u b at i o n wi t h / o ut co r t i s o l
0
2 4 hr s w i th PH A no C o r ti s ol 24 hr s w i th PH A + C o r ti s ol
Mean (95% C.I.) CD25 expression (%) on CD4 T-cells
6 0
4 0
2 0
0
4 8 hr s w i th PH A no C o r ti s ol 48 hr s w i th PH A + C o r ti s ol
Fi gur e 89a : M e a n ( 9 5 % C . I . ) p e r c s e n o t f a g e Fi gur e 89b: M ea n ( 95% C. I. ) pe rc e nt a ge s of
P H A s t i m u l a t -c e d l l s C D e 4 x p r T e s s i n g C D 2 P5 HA s t imula t ed C D 4 T-c e l l s e x p r e s s i n g C D 2 5
a f t e r 2 4 h ou r s o f i nc u b at i o n wi t h / o ut co r t i s o l a f t e r 4 8 h ou r s o f i nc u b at i o n wi t h / o ut co r t i s o l
C o n c l u s i o n :
C o r t i s o l (-)
C o r t i s o l (-)
C o r t i s o l ( + )
C o r t i s o l ( + )
C o r t i s o l (-)
C o r t i s o l (-)
C o r t i s o l ( + )
Up p e r p h y si ol o gi cal l evel s of cortis ol d id n ot alter th e e xp res s ion of C D2 5 , an acti vation
s u r f a c e m a r k e r, on P HA s ti mu lated p r o l i f e r g a t -l T i y n m p h o c y t e s s u -p b o p u l a t i o n . s
C o r t i s o l ( + )
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 68 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
S u m m a r y :
T-l ymp h oc yt e p r ol i fe rat i ve res p on s es to i n vitr o s t i m u l a t i o n w i t h m e m o r y r e c a l l a n t igen s
( P P D a n d H e r p e s ) a s w e l l a s a s u -an p e r tigen (S E B) an d a mi to gen (P HA) we re s u p p res s ed b y
th e ad d i t i on of t h e u p p er p h ys iolo gical l e vel (2 5 0 n M) of co rti s ol.
Sti m u l a t i o n b y P H s A to pl ro e a gres d s iv el y in creas in g s u r f a c e x p r e s s i o n s of b oth C D 9 5
( F a s-L : a p o p t o s i s m a r k e r ) a n d C D 2 5 ( -2 I L r e c e p t o r : a c t i v a t i o n m a r k e o r n ) C D 4 a n d -C
D 8 T
c e l l s 4 a t h o u 2 r s a n d 4 8 h o u r s i ; n an c u d b th a t e i ad o dn it ion of th e upp e r p h ys i o l o g i c a l l e v e l
( 2 5 0 n M ) of co rt is ol d id n ot alter th es e ex p res s ion s . U p p e r p h ys i o l o g i c a l l e v e l ( 2 5 n 0 M ) of
cortis ol was a l s o s h o w n t n to o a l t e r p e r c e n t a g e s o f a p t o h p e t ot i c s u r f a c e c h a n g e o s f th e cel l
m e m b r a n e ( m e a s u r e d b y A n n e x i n V a P n H d A P I s ) t o i n m -l u ymp l a ht oc e yt d es . T
A l t h o u g h t h ue n d erl yi n g mech an is ms are s till to b e e l u c i d ted a , t h e s e r e s u l w t s th at s t h ho e
u p p e r p h y s i o l o g i c e a l l ( 2 5 0 l n e M v ) o f c o r t i s o l t o s u p p r e s s T-l ymp h oc yt e p r ol ife r at ive res p on s es .
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 69 - I m p e r i a l o C n o d l o n l e g e L

Chapter IV
Discussion
- 1 70 -

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
C O N T E N T O F C H A P T E R 4
D i s c u s s i o n
4 . 1 T h e i n f l u e n c e o f p s y c h o l o g i c a l i n t e r v e n t i o n u p o n s u s t a i n e d s t r e -s
s a n d s t r e s s
a ssoc ia t ed ch an ges i n un i versi t y stu d en t s fa ci n g exa ms a nd in p at i ent s wi t h
H I V-i n f e c t i o n
4.1 . 1 T h e i n f l u e n c e o f p s y c h o l o g i c a l u i p o n n t s te res r v s e pn ercep t i o tn ion in
4 . 1 . 2
u n i v e r s i t y -i s n f t e c u t e d e a d n u l t s s a n d H I V
4 . 1 . 1 . An 1 tici p at ion o f s tres s - a c a ic d exa e mi m n at ion s b y u n ivers it y s tu d en ts
a n d a w a r e n e s s o f r c r a y i n -i g n f e c H t I i V o n t reatm b y en t n a ï ve patients 174
4 . 1 . 1 . T 2 h e i n f l u e n c e o f o l p o s g i y c h a l i n t e r uv pe on n t pi so ych n ol o gi cal
w e l l -b e i n g 176
T h e i n f l u e n c e o f h p o s l y o c g i c a l i n t e r v e n t immu i o n nu e p po aramet n e rs in u n i v e r s i t y s t u d e n t s f a c i n g a c a d e m i c e x a m s
4 . 1 . 2 1 St r e s s-a s s o c i a t c e h d a n g e s an d d ifferen ces in immu n e p aramete rs in
u n i v e r s i t y s t u d e n t s
4 . 1 . 2 Th e in fl u en ce of p s ych ol ogical in terven ti on u p on immu n e
p a r a m e t e r s in u n i v e r s it y s t u d e n t s
4 . 1 . 3 Th e in fl u en ce of p s ych ol ogical in terven ti on u p on d is eas e p rogres s ion m ark er
( C D 4 T c e l l c o u n t a ) n d s t r e s -r s e l a t e d p e -i r n f c e c e t e p d t i n i d i v o i n d u a l s 186 i n H I V
4 .1 .3. 1 D i s e a s e p r o g r e s s i o n m a r k e r a n d s -r t r e l s s a t e d p e r c e in p t H i I o V- n
inf e c t e d i n d i v i d u a l s
4 .1. 3. 2 T h e i n f l u e n c e o f p s y c h o l o g i c a l i n t e C r D v 4 e n -cells t T i o as n a u p o n
d i s e a s e p r e o s g s i o n m a r k e r -i i n f e n c t e d t i n h d e i v i d u H a I l s V
4.2 S t r e s s h o r m o n e a s s o c i a t e d c h a n g i e s n v i in t immun r o e c ells a s an exemp la r of
t h e p s y c -n h e o u r o-e n d o c r i -i n o m m u n e n e t w o r k i n t e r a c t i o n
4.2. 1 Ch an ges in N K -cells a f t e r i n v i i t n r c o u b a t i o n
4 .2. 1 . 1 N K c y t o t o x i c a c t ( i v N i K t C y A ) -c a ell n pd rofi les N K a ft er in cu b at ion o f P B M C s f or 2 4 ho u rs i n v i t r o
4 .2. 1 . 2 C o r t i s o l -i n d u c e d c h a n g e s i n N K C A l s e v e a -c n e l d l p r N o K f i l e s
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 71 - I m p e r i a l o C n o d l o n l e g e L
181
184
187
188
192
193
173
181
191

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
4 .2. 1 . 3 E n d o g e n o u s l e v e l s o f s t r e s s h o r m o n ( e s c o r t i s -S) o l a n d a n d D H E A
N K C A 194
4 .2 .2 Ch a n g e s -cells i n aft er T i n v i inc t r u o b a t i o n
4 .2.2 .1 E x p r e s s i o n o f d C u D r i 2 n 5 g p r o l i f e r a t iv e r e s p o n s e
4 .2.2 .2 Exp res s ion o f C D9 5 a n d A n n d e u r x i n g i p r n o l i f e V r a t iv e r e s p o n s e
4.3 Co n c l u s i o n s 198
4.4 Fu t u re d i r e c t i o n s
4 . 4 . 1
P s y c h o l o g i c a l i n t e s r v e n t i o n
199
4 . 4 . 2 M e a s u r e m e n t s 199
4 . 4 . 2 1 P s y c h o l o g i c a l m e a s u r e
199
4 .4 .2 .2 Immu n ol ogi cal meas u res i n v i v o
4 .4 .2 . 3 In vi tr o inve s t i g a t -cells i o n o n N K
200
4 .4 .2 . 4 In vi tr o i n v e s t i g a -l t y i m o p h n o c y o t e n s T
200
4 .4 .3 P rop os al for fu tu re i n v i v s o t u d y
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 72 - I m p e r i a l o C n o d l o n l e g e L
195
196
199
195
200

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
4 . 1 T he i nfl ue nc e of psy c ho log ic al i nte rve nti o n upo n susta i ne d str e ss a nd s t r e s s-
a ssoc ia te d c ha nge s i n u n i v e r s i t y s t u g d e xa n ms t s a nd f a i n c pa i n ti e nts w i th
H I V-i n f e c t i o n
Th is p roj ect ex ami n ed t h e h yp oth es is th at th e effects of s t res s u p o n p s yc h o l o g i c a l w e l l-
b e i n g a n d g e n e r a l h e a l t h c a n b e a l l e v i a t e d b y p s y r c h v o e l n t o g n, i o c actin a l g i tn ht rou e gh th e
in tegrat ed p s y c h o-n e u r o-e n d o c r i n o -i m m u n e n e t w . o r k
T w o g r o u p s o f i n d i v i d u a l s w i t h d i e f n f e t r l i -e f v e n t a s s o c i a t e d s t r e s s were e s s el ect e d to t e s t t h e h yp o t h e s i s :
1 . U n i v e r s i t y s t u d e n t a s c f a c d i n e g m inations i c were e x ua s ed m as an exa mp le o f
in d ivid u al s wi th s u s tain ed , b u t a time-li m ited , s t r e s s f u l s , an i t d u th a e t pi ri o mar n y
o u t c o m e s -c e l w l e p r e r e c e n t a N g e K s a n d N K C A l ; e v an e l d s
2 . H I V-i n fect ed p at i en t s l i vin g with th e on g oin g s tres s of in fecti on were u s ed as an
examp le of s u b ject s wi th s u s t a i n e d l -l i o f n e g s t r e , s s an d th e p ri mar y ou tc ome was
C D 4 -c T e l l c o u n . t s
4 . 1 . T1 he in fl uen ce of ps y ch ol og ica l interven tion u pon s tres s perc e ption in univ ers it y
s t u d e n t s -i n f a e c n t e d a d H u l I t s V
T h e f i r s t p a r t s o f is t h s e c t i d o i n s c u s s t h e e f f e c t s o f s (either t r e s s an ti ci p at ion o f e x ams f or
u n i v e r s i t y e n s t s u d o r a w a r e n e s s o f -g c a o r i r n g y i l n i -th g f reaten e o n in g d is eas e f or p at ien ts with
H I V-i n f e c t i o n ) on p s yc h o l o g i c a l w e l l-b e i n g [ 4 . 1 . 1 . 1 . ]
Th ereaft er , th e f ol lowi n g p arts o f th is s ec tion d is cu s s th e i n f l u e n c of e p s ych ol o gi ca l
in terven ti on u p on s tres s p e r c e p t i o n a n o d f f o l l o w t i h e n g c a t e g o ri s a t i o n o f t h e a p p r a i s a l o f t h e
s t r e s s f u l l if e e v e n t [ 1 . 2 . 3 . 2 ] a s:
1 . P r i m a r y a p p r ercep a i s ti a on l as : a P n e u t r a l o r b e n i g n s t i m u l u s o r a t h r e a t; a n d
2 . S e c o n d a r y a p p r a i s a l : J u d g e m e n t ’s o cap f o ab n e il it y of c op in g w i t h t h e s tres s or
s u b s eq u en t t o t h e p r i m a r y a p p r a i s a l.
F i n a l l y t h e r e s u as l t th s e y rel at e to p e r c e i v e d q u a -o l f -life, i t y i .e. p ercep ti on o f c on trol
( i n n e r o r o u t e r l o c u s o f c o n t r , o pl s) ych ol o gi cal fu n ct ion in g, an d s l e e p q u a , l a i r e t y d i s c u s s e d
[ 4 . 1 . 1 . 2 .
]
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 73 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
4 . 1 . 1 . Antici 1 p at ion o f s tres s - a c a d e m i c e x a m i n s a t b y i o u n i v e r s i t y s t u d e an n t d s awaren es s of
c a r r y i -in n fecti g on H b y I treat V men t n a ï ve p a t i e n t s
An ticip at ion o f acad emi c e x a m i n a t ns i o f o r u n i v e a r s s e x i a m t i n y e in d th s e t u d e n t s w
cu rren t s tu d y to d et ermi n e i f it cau s es in c reas es in s t r e s s l e v e . l Th s e me an P SS level of th e
u n i v e r s i t y s t u d e n t s b o t d h e m a i t c a e c x a a m i n a t i o n a n d w h e n t re h e fy ree w fr e om e xami n at ion were s imi la r to th e p u b li s h ed mean levels f o r u n i v e r s i t y s t u d e n ts [ C o h e n e t a l . , 1 9 8 . 3 In ] lin e
with p revi ou s fi n d in gs [ M a e s , V a n B o c k s t a e l e e t a l . , 1 9 9 9 ; W h i t e h o u s e e t a l . , u1 n9 ivers 9 6 ] it y
stu d en ts i n t h e cu rren t s t ud y rep orted mo r e an xiet y an d s tres s w h e n t h e y f a c e d a c a d e m i c
e x i a n a m t i o n c s o m p a r e d t o w n h th e e y we r e free fr om acad emic exa min ation s [3 . 1 . 1 ]. . Th 1 is
f i n d i n s u g p p o r t s th e v a l i d i t y o u f s i n g a c a d e m i c e x a m i n a t i as o n s a t i m -li e mited s tre s s fu l
s itu ation .
On e p os s ib le cri ti ci s m f or u s in g a c a d e m i c e x a m i n s a as t i a o sn tres s o r is th e v ari ab i li t y in
s t u den t res p ons es to a c a d e m i c e i x n a t i m o n . s Som e s tu d en ts exp eri en ce mo re s tres s th an oth ers
in res p on s e t o t h i s s i t u at i on , an d s ome c o n fid en t s tud en ts ma y e xp erien ce ver y littl e s tres s , if
a n y . M o r e o v e r lth , ou a gh exp res s ed an xi e t y at ac ad emic e xamin ati on s is u s u all y th ou gh t of as a
n e g a t i v e e x p e r i e n [ Dein c e zer & Sch u ll er, 1 9 98 ; Glas er et al., 1 9 8 5 ; Gru zelier, Lev y et al ., 2 0 0 1 ;
Gr u z e l i e r , S m i t h e t a l . , 2 0 0 1 ; Ki e c o l t-G l a s e r e t a l . , 1 9 8 6 ; Ki e c o l t-G l a s e r e t a l . , 2 0 0 , 1 so ] m e
s tu d en ts mi gh t feel ac ad emi c e x i a n a m t i o n a s r e a n o p p o r t u n i t y t o t e s t h i , s s/ o h th e at r c a p a b i l i t y
th e acad emi c e x i a n a m t i o n fs or th e m can b e p ercei ved as an e x c i t ing e xp erien ce, or in oth er
word s , a n i m p e t u in s p r i m a r y a p p r a i s a l [1 . 2 . 3 ]. . 2 F o r t h o s s t e u d e n t wh s o p ercei ve a cad emi c
e x i a n a m t i o n as s an op p ort u n it y to s h ow t h eir cap ab ilit y, th e e x a i n a m t i o n ma s y b e p e r c e i v e d a s
n ot a fea r b u t a p os i t i ve an xi ou s an ticip ation wh ich can als o c a u s e a r es p on s e towar d s figh tin g
o r t a c k l i n g f o ach r ieve men t in th e ‘f i g h t o r f l i g h t’ r e s p o n s e s i n t h e p s y c h -n o e u r o-e n d o c r i n - o
i m m u n e n e t w as o r can k b e s een in a c u t e s t r e s res s p on s es .
Nevert h el es s , th e p e r c e i v e d s t r e s s e d s ( c P a S l S e ) c a n b e u s e d t o d i s th t os i e n g wh u i o s h
p e r c e i v e t h e l i f e e v e cite n t s men a t s f rom a n th e os x e wh o p er ceive it as a s t r e s sfu l even t s in ce
th e P SS were d es ign ed to a s s e s s t h e d e g r e e t o w h i c h s i t u a t i ’s o life n s are i n ap o n pe rai s ed as
s tres s fu l [ C o h e n e t a l . , 1 9 8 . 3 Th ] is a p r i o r i e x p o s i n t oi f o th e P SS was tes ted as d is cu s s ed in th e
follo wi n g s ect i on .
Not s u rp ri s in gl y, aw a r e n e s s o f c a r l r i y -t f i h e r n e g a t e n i n g o n g o i n g d i s e a s e, -in H I fe cti V on ,
f o r p a t i e n was t s f o u n d t o m b e o r e s t r e s s f u l th an an ti ci p at ion of a c a d e m inations i c for e x a m
u n ivers it y s tu d en ts [ 3 . 2 . ]. 1 . On 1 th e ot h er h an d , an d p erh ap s con trar y t o in tu ition , t h e an x i e t y
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 74 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
levels exp res s ed b y i n d i v i d u a l s in th es e two d iffe ren t s tres s fu l s itu ation s were s h o wn to b e th e
s ame [3 . 2 . 1 ]. . He 1 n c e , i a t n c b e i m p l i e d t h a t t h e m e a s u r e d n x l i e v e t l by s y th o f e Sa tat e an xi et y
s c o r e ma y c h a r a c t e r i se m ore a n a c u t e r e s p o n of s e ‘f i g h t o r f l i g h t’ in th e p rimar y a p p rais al
[ 1. 2 . 3 . 2 ] w h e r e a s t h meas e u red lev el s of s tres s b y th e P SS ma y in d icate th e accu m u lated l e v e l s
of s tres s o v e r t h e t i p eriod m e .
N o t a b l y , a n x i e t y l e i v e l n s t -in h fect e ed H iI n d iV vi d u al s d id n ot ch an ge over th e s tu d y
p eriod , al t h ou gh t h os e rep ort in g h igh l e v e l s of s tr es s con s i s ten tl y rep ort ed mo re a n xiet y th an
i n d i v i d u a l wh s o rep ort ed low le vel s o f s tr es s [3 . 2 . 1 ]. . 1 T h i s t r e n d b t e h t two e w e e t yp n es of
i n d i v i d u a l s lab ( elled as th e S t r e s s and e d N o t -s t r e s s de efin d ed b y a mi d li n e s p li t of th e P SS
s c o r e s) w a s a l o s w o n s i h n t Imp h e act E ve n t Scal e ( IES ) m e a s u r e m e n t o f p r i m a r y a p p r a i s a l i n
e v e n t -s p e c i f i c s t r e s s p e r c e p t i o n . T h e -p
r i m a r y a p
in fection d ecreas ed o ver t h e s tu d y p eri od , b u t the levels of th es e d ecreas es were al mos t
p a r a l lel ed in th e S t r e s s an e d N o t -s tr es s ed s u b grou p s s o th at S t r e s s e d H I -in V fecte d in d ivi d u als
a l s o r e p o r ted h igh er I E S s o r e s th an th e N o t -s t r e s s e i n d d i v i d u a l [ s 3 . 2 . ]. 1 . 1
Th e fin d i n g t h at t h e s t at e an xiet y d id n ot ch an ge, b u t that t h e p r i m a r y a p p r a i s a l l e v e l d id
d ecreas e o ver t h e s t u d y p eri od s u gges ts t h e p os s ib ilit y th at th e s tres s fu l imp act of b ein g
d iagn os ed as c a r r ing y a l -t i f e h r e a t e n i n -in g fe cti d on i , can s e d ecre a s as e o , v e r t ime, H I (in V th is
c a s e a f o u r m o n t h p with e r i o a d c c e s s p s t yc o h o l o g i c a l c a r e w n h e n e e de d ) , b u t th at th e an xi et y
as s ociat ed wi t h b ei n g aware of car r yin g t h is d is eas e is les s amen d ab le to in terven tion , p o s s i b l y
t h r o u g an h ticip at in g fu tu re s tres s fu l life e ven ts related to th e d is eas e. Th is ma y in d icate th at
a n x i e t y c a n b e d r i v e n ked o r n ot p on r o ly v o f ro m t h e p r i m a r y a p p r a i s a l o f t h e s t r e s , s wh o r ich h as
o c c u r r e d i n t h e p a s t o r t h e p r e s e n t, b u t als o f r o m t h o u g h t s a b o u t an d an ticip ation of p os s ib le
fu tu re n egat ive even ts a s s o c i a t e d w i t h t h e . d i s e a s e
In c on tras t , th ere was little c h a n g e o v e r t h e f o u r m o n t h s p p e r i c o e d i v i e n d q u -o a f l -life i t y
levels , i .e . s en s e o f taki n g con tr ol o f o n ’s e own li fe m e a s u r e d b y t h e L o c u s o f C o n t r o l ( L o C )
s c a l e; level s of p s y c h o l o g i c a l f u n c t i o n i n g m a s e a s u r e d b y t h e M e n t a u l m m C a r o y m o f p o n e n t S
t h e -3 S 6 F ( M C S ); a nd level s o f s leep q u alit y a s m e a s u r e d th e b sy cal e of P i t t s b u r Sleep g h
Qu alit y In d ex (P S Q I). T hese f i n d i n g s s u g g e st th at th es e p s ych olo gical d o main s ma y b e m ore
s t a b l over e time (i .e . m ore th an th e f o u r m o n t h s u s e d i n t h i s s t u d oy r ) a m ore p ow erfu l
i n t e r v ntion e ma y b e n e e ded t o d e t e c t c h a n g . e Altern s at ivel y, th er e is a p os s ib ilit y t h at oth er
m e a s u r e m e n t s o f q u a l i t y o f l i f e d o m ma a i y n s b e mo re s en s it ive for d e t e c ting th e c h an ge th an
th e ab ove q u es t i on n ai res . How eve r, as w as th e cas e with t h e meas u res of a n x i et y a n d p rimar y
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 75 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
a p p r a i s a l , th e N o n -s t r e s s e d H I -in V fect ed in d ivi d u al s were s h own to con s tan tl y rep ort a gr eater
s e n s e o f t a k i c n o g n t r o l o f o ’s n e o w n l , i bf etter e p s ych ol o gi cal fu n ct ion in g, an d b etter s leep
q u alit y th an th e S t r e s s ind e d ivid u al s [3 . 2 . 1 ]. . H 1 e n c e , i t c a n c o b n e c l u d e d t h a t meth t h e od to comp are two S t r e s se d an d N o t -s tr es s ed s u b grou p s b as ed on th e mid lin e s p lit of th e P SS level s
m a y b e a u s e f u l a n d p r a c t i c a l w a y to i d e n t i t f h y e s t r e -related s s a n d t h e q u a -o l f -l i t i y f -related e
d i f f e r e n c e s i n th e m e as u rem en ts in th e p s y c h o-n e u r o-e n d o c r i n -i o m m u n e n e t w . o r k
4 . 1 . 1 . T 2 h e in f l u e n c e o f p s y c h o l o g i c a l i n t e r p s v y e c n h t o i l o g n i c l u a w p o e n l l-b e i n g
As d es cri b ed i n t h e In t rod u ct ion [1 .2 .3 ], t h e s t r e s s p ercep t ion to b e e xamin ed in th e
p r o j e c t w a s t h e p a r t i c i ’ p a ap n p t r s a i s a l o f s t r e s s f u l l i f e e v e n ts. Th e res u lts fr om b ot h s tu d y
p op u lat i on s i nd i cat ed t h at t h e p s ych olo gi cal in terven tion s h ad n o clear b en efit u p on s t res s
p e r c e p t i o n a p n e d r c e i v e d q u -o a f l -life. i t y T h e r are e a n u mb er o f f act o rs th at c o u l d exp lain th e
g e n e r al l y n e g a t i v e r e s u l t s :
1 . P s ych ol o gi cal in ter ven tion s ma y n ot i mp act u p o n t h s e t r e s s p ercep ti on meas u red in
t h e c u r r e n t s t u d ; i e s
2 . Th e s h ort p eri od of ti me in train in g an d p ractice of th e p s ych ol ogic al i n t e r v e n t s i o n
f o r a c h i e v i n g t o s h o w c l e a r e ; f a f n e c d t / o s r
3 . T h e rel at i vel y s mal l s amp le s izes .
D e s p i t e t s e h e n e g a t i v e r e s u l t s , d a ta f r o m s o m e o f p st ych h e ol o gi cal m e a s u r e s, i .e .
p e r c e i v e d q u a -o l f -life i t y (s p eci fi cal l y, t h e L o C , M C S a n d P S Q ), I in d icat e s o m e b e n e f i t fr o th m e
J o h r e i i n t e r v e n t i o n o n t h e s e n s e o o n f t r t o l a k i o n f g ’s o c n e o w n l , i pf se ych ol o gi cal f u n ct ion in g,
a n d s l e e p q u . a Sleep l i t qy u al it y ma y al s o in d icate s en s e of con tr ol in th eir life , p art icu rl y in th e
s e n s e o f c o n t r o l i n r e l a x a t i o n a t n i g h t-tim e b oth co gn itivel y an d p h ys icall y, s o ch a n ge levels in
s l e ep q u al i t y ma y al s o rep res en t ch an ges in th e s en s e of con t r ol . T h e s e b e n e f i ts m a y h a ve b een
c l e a re r h ad t h e s t u d y i n v o l v e d a g r e a t e r n u m b e r o f (e.g. s u b j e mc ore t s th an 1 2 1 for th e LoC an d
P S Q I o r 1 3 3 f o r t h e M C . S )
T h i s s e c t i o n d i s c u s s e s t h e olo e f gical f e c t in ter o f ven p ti s on y c uh p on th es e s tres s
p e r c e p t i o n ( p r i m a r y a n d s e c o n d a r y a p p r a i s a l s ) -o a f n -life d p e a r s c f e o i l l v o e w . d s q u a l i t y
P r i m a r y a ppr a i s a l
A m a j of o r s tres s man a i age m men t in terv en tion is to alter th e p rimar y a p p r a i s a l o f t h e
s t r e s s f u l l i f e e v e n t ro f m a t h r e a t t a o n eu tral (o r e v e n a b e n i g n s t i m u ) l [1 u s .2 .3 .2 : T ext b o x 2 ] s o
t h a t t h e e v e n lon t gi er s p ercei n o ved as s t res s fu l . Th is was aimed t o ach iev e b y p r o vid in g
altern at i ve p ers p ect i ves [1 .2 .3 .3 : Te xt b o x 4 ].
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 76 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
I n t h p e r o j e c t , t h e u n i v e r s i t ts y in s th t e u Rd el e axat n ion c on trol gr ou p exh ib ited in creas ed
l e v e l s o f t h e S t a t e a n x i e t y s c o r e s w h e n t h e y w e r e f a , c a i n d g th e x a m ps yc s h o l o g i c a l
i n t e r v e n t i o n s d i d n o t s h o w a n y e e c f t f s o n t h i e n c r e a s e i n S t h a e t e a n x i e t y s c o r ]. e s Th is [ 3 . 1 . 3 . 1
f i n d i n m g a y b e in terp ret ed as th ei r p ercep tion of th e exa ms was n ot ‘n e u t r a l ’ in th e p rimar y
ap p rais al cat ego r y. A s d i s c u s s e d b e f o r . e 1], th [ 4 e . S1 tat . e 1 an xi et y s c ores migh t re p res en t th e
s u mmed level s of an ti ci p at ion of b oth th r eat an d imp etu s , s o th ere re main s a p o s s ility i b that
s ome of t h e p art i ci p an t s mi gh t h ave b een ch an gin g th e wa y th e y view th e exa m as a wa y t o c op e
w i t h t h i s s t r e s s , o r o r e v e n a w a -l y i t o f u o t p r a l e t o t tac h kl e th e em xams . Hen ce, f u tu re s tu d ies
u s i n g u n i v e r s i t y s t u d e n t s s h o u l d i p n o v t e h e s t i s i b g y a t m e a s t u h r i n s g t h e y l e v e l s o f
e x c i t e m e n t a s w e l l a . s a n x i e t y
Similarl y, th ere w as n o ch an ge in th e S t a t e a n x i e t y s oc ver o r e th e fou r m on th s p eri od in
t h e -in H fected I V in d ivi d u al s in ei th er th e w a i t -listed con tr ol g rou p o r th e in terven t ion gr ou p s .
O n t h e o t h e r h a n d , th e IE S s c o r e s d i d d e c r e a s e i g n i f i c a n t l y a s d e s c r i b e d b e , f b o u r t e th ere was
n o d i f f e c e r e i n n t h e d e c r b e e a s t e w e e n t h e p s y c h o l o g i c a l i n t e s r an v d e n th t e i w o a n i t -listed con trol g r o u ps. O n e p o le s s exp i b lan at ion f or th e i m p r o v e m e n t i n t i h e r S I s c E o r e s n o t e d o v e r t i in m th e e
w a i t -listed c o n t r o l g r m o i u g p h t b e r e l a t e d t o th e t i m i n g i n m e a e s u q r u e i s n t g i o t n n h a i . r Du e e t o
p r a c t i c a l d i f f i c u l t i e s i n a s k i n g t h e p a r t i c i p a n t s t o f i l l i t n h e t h e q u e s t i o n n
w a i t -listed c o n t r o l u g p r co o mp let ed th e q u es ti on n aires s h ortl y b efo re (an d f or s om e of
p a r t i c i p a n , t ds u rin g) th e fi rs t week of ei th er o f th e p s ych olo gical t rain in g s es s ion . Hen ce, a
p o s i t i v e a n t i c i p a t i t o n h fo e t rth o w com a r id n g p s y c h o l o g i c l a in ter ven ti on aft er a l on g waitin g
p e r i o d mi gh t e xp lai n , at leas t in p art, th e o b s e r v e d i m p r o v e m e n t i n t h i s . d o m a i n
Non eth el es s , t h e p s ych ol ogi c al in terven ti on s s h owed n o gr eater i mp ro vem en t or
a l l e v i a t i o n i n t h e S t a t e a n s x c i o r e t s, r y el at is ve c o to r th e s w a o i t r -listed t h c e o n t I r E o S l g r o u p
i n -p H atien I V ts .
Se c o n da r y a p pr a i s a l
Th e P S S s cores s h owed n o d iffer en ce b etween th e in terven tion g rou p s an d th e R elaxation
con trol gr ou p at acad emi c exa min ation s , s o it was c on clu d ed th at th e p s ych ol ogi ca l in terven tion
d id n ot affect th e p e r c e i v e d s t r s e s levels in u n ivers it y s tu d en ts facin g acad e mic e xa min ation s
mor e th an t h e rel axat i on mi gh t h ave d on e .
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 77 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Th e s c o r e s o f t h e P -i S n f S e c t e i d n i n d i t v i h d u e a l s H a I t V r e c r u re i t mu m e ch n t h igh w e er
t h a n t h e l e v t e h l e s u n i v i e n r s i t y s t u d e n t s fa c i n g e x a m s , a n d t h e levels s ta yed at th e s ame h igh
levels a f t e r f o u r m o n t h s p e r i o w d a i t -listed n t h e c o n t r o l g p r a o r t u i p c i p a n . t More s o ver, th e fou r
mon th s of t rai n in g an d p ract ice in th e p s ych ologic al in terven tion s d id n ot c h a n g e t h se e h igh
P S S s c o r s. e T h i s f i n d i n g s u g g e s t s th a t p e r c e i v e d s t r e s s l e v e l i n -in fected H I V in d ivi d u al s was
n o t a f f e c t e t d h e b y p s y c h o l o g i c a l i n s. t e I r t v e n i t s i o p n o s s i b l e t sh tres a t s level t h e s h i g h
a s s o c i a t e d -p o w s i t i v ma h e y nb ot e b e i amen n g ab le H to I ch V an ge with th e b rief in terven tion s
u s e d i n t h is s t u d y . I t i s a l s o p o s s i b l e t h a t t h e r e l a t i v e l a y n d s m s a h l o l r t s a m t p i l m e e s i p z e r i o d
limited t h e p ower t o d et ect s i gn ifican t eff ects th at migh t h ave b een s h own h ad th ere b een mor e
p a r t i c i p a n t s a n d a l o n g e r i n t e r v e n t i o . n t i m e p e r i o d
N o v e r t h e l e s , s it is c o n c l u d e d t h a t t h e p s yc h o l o g i c a l i n t e r v e n t i o n s s h o w e d n o s i g n i f i c a n t
i m p r o v e m e n t o r a l l e v i a t i o n i n t h e P e r c e i v e d S t r e s s S c r a l e l a s c t o i r th e v s e rel t ax o at ion in u n i v e r s i t y s t u d e n t s f a c i n g th e w x a m i t -listed s o r c o t n o t r o l s i n -p atien H I ts V .
Quality-o f -life
T h e eas u res m o f p ercei ved c o n t r o l ( l o c u s o f c o n t r o , l p) s ych ol o gi cal fu n ct ion in g, a n d s leep
q u alit y d id n ot ch an ge in th e w a i t -listed c on trol gr ou p i n t -in h fected e H iI n d iV vi d ual s ove r th e
f o u r m o n t h s p . e Mr ore i o ove d r, n e i t h e r o f t h e p s yc h o l o g i c a l i n terven tion gr ou p s s h owed an y
s tatis tical d i fferen ces i n t h es e levels a fter fou r mon th s of t h e in ter ven tion p eriod . Howeve r,
alth ou gh a larger s a mp le s ize w o u l d b e n e e d e d c t o , n th f ere i was r a m t r e n , d i n t h e J o h r e , i g r o u p
for imp ro ved s co res ac ros s all th e t h r e e o u t c o m e d o m a i . n Hen s ce, th ere re mai n s a p os s ib ilit y
t h a t t h e t r a i n i n g a n d p r a c t i c e o f J o h r e i h a s i -o m f -l p r i f o e v e l d e v e p , l e wh s r c ich e i can v e d q u a l i t y
b e a s s o c i a t e d w i t h i m p r o v e m e n t -focu i n st ed h e cop m in e g a sn ki i ln ls g [1 .2 .3 .2 : Te xt b ox 3 ].
T o g e t h e r wi th th e cl ear d i f f e r e n t t r e n d s i n t h e e f f e c t u p o n t h e i m m (d u is n cu e sc se ed l l s
b elow [4 .1 .2.2 an d 4 .1 .3. 2 ] ), a n d t h e f a c t t h a t t h e e f f e c t s e e m e d f a v o u r a b l e t o J o h r e for i
u n i v e r s i s t u d y e n ts [ 3 . 1 . ] 3 an . 2 d H I -i n V f e c t e d i n d i v i d u a [3 l . s 2.2.2 a n d 3 . 2 ], . it 3 . is 2 s u gges ted that u n i qu e p s ych ol o gi cal f eatu res in th e J oh rei train in g an d p ractice ma y b e worth wh ile to
exp lore fu rt h er.
T h e t r a i n i n g a n d p r a c t i c e o f t h e -a s e d l m f i n i s t e pr s e ych d ol o gi cal in ter ven ti on u s ed in th e
p r o j e c t a i m e d t o a c h i e v e t w o o b j f e o c r t i t h v e s p a r t i c i p a n t s :
1 . B e h a v i o u r a l d o m a i n : s p e n d i n g t i m e a n d e f f o r t o n ’s o n e o s w e l n f b f e o n r e f o i n t e ; a n d
2 . C ogn i t i ve d o mai n : acq u i rin g ad d ition al c on cep ts an d p ers p ectives for s tres s fu l e ve n t s .
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 78 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
I n t h e b e h a v i o u r a l d o m a i n , o n e o f t h e u n i q u e f e a t u r e s o e f i J p o r h a r c t i c e i s t h a t ei qt ur ires
a p artn er to p r a c t i s e w i t h w h i l e t h e S -h e l y f p n o s i s p r a c t i c e r e q u i r e s ’s o n own l y o ti n me e an d
e f f o r t . Th i s i n vol ve men t o f oth ers as a p a rtn er / rec eive r f or th eir own J oh rei p racti ce co mes
f r o m t w o o f i t s k e y c o n c e p t s a n d p r in cip les [ N a i t o , 2 0 0 3 : ]
1 . “H e a l i n g o n e s e l f b y h e a l i n g o ”: t h e e r s a l i n g i s a m u t u a l oces p r s an d in teract ion , a n d
i t b e n e f i t s e q u a l l y b o t h t h e J o h r e i g i v e r a n d r e c e i v e r s i n c e t h e p o hw ealin e r o g f w a s
t a u g h t t h o se p iritu a al r h e i a l s i -l n e g igh t wh f ich r fl o ows m th rou gh giv er an d recei ver
d u r i n g t h e J o h r e i p r a c t i c e ; a n d
2 . ‘S p i r i t u a l ’: c o r w ere d h th e s p iri tu al h e a l i -li n g gh t an d love co mes an d tra vels b e yo n d
t i m e a n d s p a c e , a n d t h i s S p i r i t u a l c o r d b o n d s a J o h r e i g i v e r w i t h a l of l th e p e op le wh om t h e gi ver cares ab ou t an d als o with s ometh in g greate r in th e s p iritu al realm , i.e.
th e s ou rce o f th e s p i r i t l u light a itself.
C o n t i n u e d p r a c t , i w c e h i c h i s a c o m m o n f e a t u r e i n b o t h J o h r e i a n d -h yp S e nl f os is , c an al s o
en h an ce a t rai n ee’s s en s e of c on fid en ce in h is or h er o wn skills, th e m an ageab ilit y in cop in g
s t r a t e g i e s [ 1 . 2 . 3 . , 2 wh ] ich can b e rep h ras ed as ‘S e lf-e m p o w e r m e n t .’ T h e a b o v e t w con o cep ts fou n d in th e J oh rei p ract ice, th eref or e, ca n b e s tren gth en ed s y n e r g i s t i with c a l l an y in creas e in th eir ‘Self-e m p o w e r m e n t ’, as th e y are rep eated in p ractice.
I n t h e c o g n i t i v e d e o s m e a t i a n , g i b t l e h c o n c e p t s m a y o ha ave l s p r ovi d ed a J oh rei gi ver
with b ot h a s en s e of s u p p o - r an t d a s e f n s r e o f m c o n n e c t e d - n e a s r s e c e t i v o e r, an d even
s o m e t h i n g g r e a t , i . e . t r h e s o u i r c e n o f t h t e l i h g h . e t Th is s ma p y hi a ve r b ui ffered t u a l r e a l m
a g a i n s t f a e n e y l i n g s o f l o n e l i n e s s o r h e lp l e s s n e s s, a n d c o n t r i b u t ed t o a n o v e r a l l s e n s e o f w e l -l
b e i n g [ F r o m m , 1 9 5 6 ], c o n s i s t e n t w ith th e fin d in gs fro m the W h i t e h a l l S t u d y I I w h i c s h owed
t h a t s o c i a l s u p p o r t a n d self-c o n f i d e n c e a b o u t ’s o n own e s ki ll s are i m p o r t a n t f a c t o s r f o r th e
p r e v e n t i o n o f p oo r men tal h e a l t [ S h t a f f o r d & M a r m o t , 2 0 0 3 ; S t a n s f e l d e t a l . , . 1 9 9 7 ]
F u r t h e r m o r , a e b e l i e f a n d e n c o e n f i n d o n s e l f / a o n r d s o m e t h i n g g r e a t e r m i g in h creas t h a ed v e
t h e m e a n i n g f u l n e as s s Fr om m [1 9 5 6 ], Fr an kl [1 9 7 0 ] an d S t r a n g e t a l . [ 2 0 0 1 s u] gg es ted .
A c c o r d i n g l y , J o h r e i m i g h e t n h a h n a c v e d t h e i r a b i l i t i e s i n -f ocu t h se ed m co e pa i n i g n g
a p p r o a c h a s w e l l a s th e e m o t i - o n o r - p f o r c u o s e d b a l p p r e o a c m h e s [ 1 . 2 . 3 . 2 : T e x t b o x . 3 ]
I n a d d i t i o n , t h e tw a b o cv on e cep ts , gi v e n rep eat ed l y in th e J oh rei p ractice, h ave p rovid ed
th e p art i ci p an t s wi t h a ch an ce to recall or to gi ve in s igh t ab ou t th ei r own p ers p ectiv es related to
‘Spirituality’. Th e word ‘Spirituality’ or ‘S p i r i tu a l ’ ma y s u gg es t va riou s con cep t s a ccord in g t o
each in d ivi d u al and each occas ion or s itu ation [ R i c h a r d s & B e r g i n , 1 9 9 . 7 In ] th e J oh rei trai n in g
s es s ion , t h i s vari et y of ‘Spi r i t u a l ’ th ou gh ts an d con cep ts are allowed an d s h ared in a gr ou p , an d
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 79 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
c o u l d b e l e f t i n a m b i g u i t y i f t o t a l a g r e e m e n t c o u l d n o t b e a c h i e e v e to d , feel a s l o n g a s t h e y
c o m f o r t a b l e t o p r a c t i s e J o h r -ii]. e i [ A p p e n d i x 2
Th e J o h r e i p a r t i c i p a n t s a w l e s en r o e cou ra ged to ap p reci at e th eir own d ou b ts ab ou t th e
efficac y of th e in ter ven ti on , o r th e e x i s t e n c e o f t h e -ligh h e t a if l di ou n g b ts ab ou t th es e aros e
n a t u r a l l y . T h e e s d o u b t s als c a o n b e left in amb igu it y al th ou gh th e y wer e als o en cou raged to
p ractis e even wi t h d ou b t s s o th at th e y can tes t or ch allen ge th e d ou b t s b y th e ms elve s [ Ap p en d ix
2-ii] i n o r d e r t o m a i n t ’s a i n i n n o e n r e c o h e r e . n Th c e es e met h od s u s ed in th e J oh rei s es s ion are
b as ed on th e con cep t th at a m b i g u i t y m a y p r o v i d e i m p o r t a n t i n s i g h t s i n t o -c s o e g l f n i t i o n o f ’s o n e
own life [ E m p s o n , 1 9 3 0 ; T o y a m a , 1 9 7 , 3 s] o th at th e in d ivi d u al s left in a m b i g u i t y ma y b e ab le to
( 1 ) e s t a b l i s h a n a l t e r n a t i v e p e r s p e c t i v e t o c o p e w i t h s t r e s s f ; u l ( 2 ) l ach i f e iev e v e e a n gt s rad u al
i n c r e a s e o f th e i r i n n e r-p e r s o n a l c o h e r e n [ c A e n t o n o v s k y , 1 9 9 3 ]; an d (3 ) weigh val u es an d goals
t o m o d i f y t h e m e a n i n g o sf s fu a l t s r t a r n e s a c t [ i F r o a n k l , 1 9 7 0 ; P a r k & F o l k m a n , 1 9 9 to 7 ]
i n c r e a s e t h e s e n s e o f m e a n i n g f u l [1 n . e 2 s s . 3 . 2 . ]
Th e p os s i b l e l i n k b e t w e en t h e ab ove b eh aviou ral an d c ogn itive d omain s i s f ou n d in a
con cep t of ‘S e l f -c u l t ivation’ [ Y u a s a & K a s u l i s , 1 9 8 7 ; Y u a s a e t a l . , 1 . 9 Th 9 3 is ] ‘S e l f-cultivation’
ma y n ot b e exp l i ci t l y rec o gn is ed in Wes t ern cu ltu re, b u t it h as b een emp h as is ed in Eas tern
cu ltu re in cl u d in g vari ou s trad ition al J ap an es e p ractices [ Y u a s a e t a l . , 1 9 9 . 3 Th ] e mot t os o f th is s e l f-cu lt ivat ion in cl u d e “p r a c t i c e m a k e s p e r f e c t” an d “p r a c t i c e p r e c e d e s k n o w l .” e d Th g e es e
m o t t o s m e a n t h a t p r a c t i c e d o e s n o t r e q u i r e a f u l l u n d e r s t a n d i n g o f k n o w l e d g e i n t h e s u b j e c t, b u t
b en efit s can b e ob t ai n ed , an d s kills an d kn owled ge can b e d evel op ed th rou gh b as ic p ractice o f
‘K a t a’ - a s t a n d a r d f i o r s m e d o r s e q u e n c e o f e x e r c i s [ e Y s u a s a & K a s u l i s , 1 9 8 . 7 The ] id ea is that
p r actice can b e u s e d t o d e , v an e l d o al p s o to b ri n g t o t h e f of o r con e s ci ou s a w a r e n e ss , ‘Tacit
k n o w l e d g e’, i .e. kn owl ed ge th at wou ld ot h erwis e r e m a i hn id d en [ N o n a k a & T a k e u c h i , 1 9 9 5 . ]
C ollecti vel y, t h e d evel op men t of th e ab o ve d o main s s h ou l d res u lt in th e followin g gain s :
1 . S o c i a l p p s o u r t a n d s e n s e o f s u p p o r t ;
2 . S p i r i t u a l a w a r e n e s s ; a n d
3 . I n n e r -p e r s o n a l c o h e r e n c e m e a n i d n g f u l n e . s s
H e n c e , f u t u r e i n v e s of t i J oh g a rei t i so hn o u ld in cl ud e examin ation o f th e ef fects on
p e r c e i v e d s u p p o r t h e a s n e d q u a l -o i t f -l y i f e d o m a i n s u s i n g p q u b e l s t i s o n h n e a d i r e th s at as s es s
t h e s e c o n s t r u c t s , s u c h th e a s K e s s e l e r P e r c e i v e d S o c i a l S u p p o r t ( K P S [ S C ) o v e n t r y e t a l . , 2 0 0 , 4 ]
th e S p i r i t u a l I n v o l v e m e n t a n d B e l i e f s S c a l e ( S I [H B S a ) t c h e t a l . , 1 9 9 8 a ] n d th e Sens e of
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 80 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
C o h e r e n c e ( S o C ) [ A n t o n o v s k y , 1 9 9 3 ], a s w e l l a s th e s c a l e s o f s t r e s s , u p s e r d ic n e tp ht e i o n
p roject s u ch as th e P ercei ved Stres s Scale (P SS) [ C o h e n e t a l . , 1 9 8 , 3 ] a n d s l e e p q , u th a e l i t y
P i t t s b u r g h S l e e p Q u a l (P i SQI) t y I [ B n u d y e s x s e e t a l . , 1 9 8 . 9 ]
4 . 1 . T 2 h e i n f l u e n c e o f h p o s l y c o g i c a l i n t e r u v p e o n i mt mu i o n e pa ra me ters in un i ve rs ity
s t u d e n t s f a c i n g a c a d e m i c e x a m s
Th e ch an ges in p ercen tages o f -c N e K l l s -cells a n d at acad T emi c exa mi n at ion time were
s m a l l , a n d s i m i l a r i n th e d eg ree of ch an ges fou n d els ewh ere in th e literatu re u s in g u n ivers it y
s tu d en ts [ Gr u z e l i e r , 2 0 0 2 b ; Gr u z e l i e r , S m i t h e t a l . , 2 0 0 1 ; Ha l v o r s e n & V a s s e n d , 1 9 8 7 ; Ki e c o -l
t
G l a s e r e t a l . , 1 9 8 6 ; M a e s , V a n B 9 o 9 c ; k U s c t h a e k l i n e e t e a t l . , a l 2 0 . 0 I , 1 n ] g 1 e 9 n d e r
d i f f e r -cells e n c h ave e , b een rep N K ort ed t o b e low er in fe males th an males u n d er the age of 5 0
[ J e n t s -U c h l l r i c h e t a l . , 2 0 . 0 Th 5 ] i s s t u d s y h o w e d t h e s a m a s e n o t g e r n d e ias r n d b , b u t t
with regard t o s t res s [3 .1 .2 .3 ]. Si milar flu ctu ation s were al s o rep ort ed in s tu d ies that u s ed
s l i g h t l y d i f f e r e n t i m m u n o-p h e n o t y p i n g : C D 2 w a s t u o s e d g -c a t e e l l T s -cells & in s tead N K of
C D4 5 [ M a e s , V a n B o c k s t a t e l a e l . , e 1 9 9 , 9 an ] d C D1 6 w a s c o m b i n e d w C D5 i t 6 h t o d e t e c t N -K
cells [ d e G u c h t e t a l . , a k 1 i n 9 9 e 9 t ; a l . U , c 2 h 0 0 .�H 1 ] e n c e , c h a n g e s a n d d i f f e s r he ere n c e ma y
h ave n o ap p aren t cl in ical imp acts u p on h ealth , b u t th e r e s u l t s a r e d i s th c u e s ligh s e d t of i sn tres s
res p on s es .
4 . 1 . 2 1 S t r e s s-a s s o c i a t e d c h a n g e s a n d d i f f e r e n c e i n s i m m u n e p a r a m e t e r s i n u n i v e r s i ty s t u d e n t s
T h e l e v e l s o f l y m p h o -p c y o t e p u s u l b a t -c i e o l n l s , ( C N D K 4 -cells a n d ) an C d D th 8 e NK T
c ytot oxi c act i vi t y (N KC A) w ere an al ys ed b y co mp arin g th e S t r es s ed an d N o t -s t r e s s e d
s u b g r o u p s i t n h un e ivers it y s tu d en ts . A l t h o u g h t h -c e l l r p e r s c e ges n u t l a f rom t s th is o f N K
s t u d y d id n ot s u p p ort p revi ou s f i n d i n g s i n t h e l i in t e wh r a t ich u r se tres s ed s t u d e n t s h ad lo w e r
n u m b e r s or p ercen t age o f N K -cells in th eir c i r c u l a t i o n c o m p a r e d w i t h n o t-s t r e s s e d s t u d e n ts , the
res u lts s h owed th at th e S t r e s s e s t d u d e n t s e x h i b i t low N KC A le vels c omp ared with th e N o t -
s t r e s s e tu d e n ts [3.1 .2 . 1] in li n e wi th pub lis h ed find in gs [d e Gu ch t et al., 1 9 9 9 ; Dein zer &
Sch u ller, 1 9 98 ; Gl as er et al ., 1 9 8 5 ; Gru zelier, Smith et al., 2 0 0 1 ; Halvo rs en & Vas s en d , 1 98 7 ;
Ki e c o l t -G l a s e r e t a l . , 1 9 8 . 6 ]
T h i s f i n d i n g l e a d s t o t h e at ih ny dp ivi o t dh ue al s i w s i t h
h i g h s t r e s s levels , f r o m
s u s t a i n e d s t r e [1 s s .2 .3 .2 ], ma y h a v e l ow NKC A l evels r e g a r d l e s o f t h e s i . t Th u is a t i o n
h y p o t h e s i s m a y b e s p e c i f i e d sm u ch o r e th at th e h igh p ercei ved s tres s le vel ma y b e a s s o c i a t d
e
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 81 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
with a l o w p e r-N K -c e l l c yt o t o x ic a c t i v level. i t y N K -c e l l p e r c e n t a g e s N K a c n y d t o t o x i c a c t i v i t y
m e a s u r e d b y u s i n g P B M C are s oft en u s ed t o g e t h e r s o e p a r a t as e sl tres y s b en ch marks wi th ou t
c a l c u l a t i t n h g e p e r-N K -cel l c yt ot o xi c a ct i vi t y [Dop p et al. , 2 0 0 0 ; Lev y et al ., 1 9 8 9 ; Sch ed lows ki
e t a l . , 1 9 9 3 ; W h i t e h o u s e e t a l . , . 1 T 9 9 h 6 i ] s p e r-N K -cel l c yt ot o xi c acti vit y, calcu late d as a N K
c e l l p e r c e n t a g e t o y t N o K t o c x i ac ctivit y r at io, is kn own to b e imp aired in certain p h ys ical
c o n d i t i s, o sn u ch as in ci rrh os is [ La s o e t a l. , 1 9 9 7 ] an d end omet ri os is [ O o s t e r l y n c k e t a l . , 1 9 9 . 4 ]
I n s t r e s s r e s e a r c h , o n -a e n a m l e y t s a i s p a r p c e a l c u l a t e d t h i s p -N e r K -cel l c yt ot o xi c ac ti vi t y
i n a c u t e s t r e s s s e t t i n g s , a n d m e n c t u i t e o n s e t d r e s t s h d a i t d a n o t a l t e r -N p e K r -cel l c yt ot oxi c
a c t i v i t y , i . e . -i s t r n e s s d u c e d c h a n e g r e s d u e i n t o N K C a A -c l ell w t pe ercen r a tages t i o n o f N K
[ S e g e r s t r o m & M i l l e r , 2 0 0 . 4 ] h is T ma y o n l y occu r in acu te s tr es s situations , given th e fin d in g
that acu te s tres s c a n i n c r e a s -cel e l pb ercen o t tage h an d N NK KC A le vels [ D o p p e t a l . , 2 0 0 . 0 ]
T h e r e f o r e , i t i s s u g g e s t e d t h a t f -cells u t u r e s t u d i
s h o u l d a n a l y s e t h e p -N e r K -cel l c yt ot oxi c act ivi t y.
In th is cu rren t s t u d y, in th e S t r e s s se tud d en ts , t h e l e v e l s o f p e t r -N h e K -c e l l c yt ot oxi c
a c t i v i t a y n d N e w K r C e f A o u n d t o b e l o w , e alth r ou gh N K -c e l l p e r c e n t a g e s w e r e n o t d e c r e a s e d
[ 3 . 1 . ]. 2 . T 1 h i s i m p l i e s t h a t t h e r e m a y b e o t h e r f a c t o r ( s ) a f f e c t i n g N KC A t h a n a s i m p l e c h a n g e n i
N K -cel l n u mb ers / p ercen t ag es . Th is was in ves tigated b y lo o kin g f or d ire ct ef fects of i n v i t r o
e x p o s u r e o f b l o o d t o c o r t i s o l [ 3 . 3 ] a n d i t s h w i l l d i b e s c u s s e d l a .1]. t e r [ 4 . 2
I n t h a e n a l ys i s o f C -cells D 4 T ( H e l -l p e y r m p T h o c y t e s a n d -c R e e l l g s ), u th l e a r t e s o u l r t s y T
s h owed th at th ere was n o s ign ifican t d i f f e r e n c e i n t h -cells e l b e et wee v e l n ts h e o f C D 4 T
S tr es s ed and N o t -s t r e s s e u d b g r o u p s. T h i s r e s u l t is in lin e with p reviou s r e p o r t s; s o me s tu d ies
rep ort an in creas e , ot h ers a d e c r e a s e, a n d s t i l l o r t h e n r o s c h r a e n p [d g o e Gu ch t et al ., 1 9 9 9 ;
M a e s , V a n B o c k s t a e l e e t a l . , 1 9 . 9 T 9 h ] e p o s s i b l e c h a n g e or s n o c h a n g e in th e C D 4 T-cell
p e r ce n t a g e s m a y b e d u e : t o
1 . A c h a n g e o f d is tri b u ti on in C D 4 -c T e l l s a n d / o r in s u b s e t s ( T h , . Th 1 .2 a n -r d e g ) T , i. e.
a r e l e a s e o f c e l l s i n t o t h e or c i hr omi c u nl g a of t i cells o n i n t o t i s s u ; e s
2 . A ch an ge in rat e of cel l p r o d u ction, i. e . e n e g r a t i o r n i o n h i b i t i o n o f n e w ; c o e r l l s
3 . A ch an ge in c e l l st d e r u c t , i o n i . r e v . e n t p i n g o r p r o m o t i n g c e l l d eath (p ro gra mmed cell
d eath in the c e l l c y c l e . )
T h e s e s c e n a r i o s occu m a r y in a s p eci fi c t i m e c o u r , s tartin e g wi th a cel l d is tri b u tion ch an ge an d th en g e n e r a t in g n ew cells an d th e p r e v e n t i o n o f c e l l . Th d is e a con t h s ecu ti ve c o u r se
ma y refl e ct a s h ift f ro m an ala rm reacti on t o a s t a g e o f r e s i s alon t a n g c e th e li n es of Sel ye’s
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 82 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
c l a s s i f i c a t i o [1 n s . 2 . 4 ]. . T 1 h i s a l a r m r e a c t i o n m e a n s t h a t p e r c e i g v a i n s it u a t i o n a s s t r e s a s n f bu e l c
res p on d ed to i n t h e i m m u n e a r m o f -n t e h u e r o-e p n s d y o c h r o i n -i o mmu n e n et wor k b y a r e l e a se
o f C D 4 -c e T l l s i n t o t h e c i . r Th c u is l p a o t s i s i b o n l e mech an is m in th e immu n e s ys t e m was
s ug g e s te d in a rep ort s tat in g that t h e i n c r e a s e i n b t l h o o d f t s h e t -c r C e l D e l 4 s a w m T a ds u e to
an in creas e of on e s u b s e t o f 4 -cells T C D (C D 2 5 + C D 4 + T-c e l l s u b s e t ) in n u rs es u nderg oin g
s u s t a i n e d s t r e , s s i . e . n u r s e s w h o d i w a e g r s n e o e d with ‘ b u r n o u t ’ s yn d r ome [d e Gu c h t et al.,
1 9 9 9 ] . Th is C D 2 5 + C D 4 + T-c e l l s u se b t is a mai n c omp on en t o f th e R e g u l a t -c o r e y l l -re T s g) ( T
wh ich p l a y a m a j o r r o l e i n n e a r gy, t ol era n ce or i s n w i t c h i n g o f f i m t m h e u n e r e s p o n s e to
p ath ogen s [ A k b a r e t a l . , 2 0 0 , 3 ] s o t h i s c o u l n d imp b e ort a an t fact o r in th e s u p p res sive ef fect of
s u s t ain ed s t res s u p on t h e i mmu n e r e s p o n s e s.
R e c e n t l y , t h e d i r e c t i o n o f -i s n t d r u e c s e s d c h a n g e s i n C D -c 4 e l T l p e r c e n t a g e s , w h e t h e r t o
i n c r e a s e o r t o d e c r e a s e , dw emon a s s trat e d to d ep en d up on th e c o n d i t i s o of n th e s tu d y, i . e. t yp e
o f s t r e s s o r a n d t i m i n g T-c w e h l e l n C p e D r 4 c e n t a g e s w e r e , as m se ha own s u r be el d o w
[ S e g e r s t r o m & M i l l e r , 2 0 0 . 4 Th ] e cat eg or ies of d et ai led s ettin g of th e ti min g in th e reviews
[ M i l l e r & C o h e n , 2 0 0 1 ; S e g e r s t r o m & M i l l e r , 2 are 0 0 4 wh ] et h er th ere is s h o r t l a s t i n g - t i m e
l i m i t e d a c u t e s t r e s s o r o n e t o f h e f o l l o w i n g f o u r c a t e g o r i e s o f s u s t a i n e d s t r e s s :
1 . Br i e f n a t u r a l i ( p s r t e d i c t a b l e s e -l l f i m i t e d l i f e e v e n t s , e . g . a c a d e m i c e x a m i n a , t i o n )
2 . Ch r o n i c -g ( o n i n g o r p e r s i s t e n t l i f e e v e n t, e . g . d i ), s e a s e
3 . Even t s eq u en ce (d is cret e s t r e s s f u l e v e n t s o c c u r r e p e a t e d l , y ) o r
4 . Distant (p as t b u t t rau mat ic even ts ).
T h e s u s t a i d n s e t r e s s i n th e c u r r e n t s t u d e n t s tu d y falls in to th e b rief n atu rali s tic s tres s , an d
t h e y m e n t i o n e d -c e l t l s h s ee a med t C n ot D 4 to ch T an ge in n u mb ers , b u t fu n ction al s u pp res s ion
o r a s h i f t t o w a r d s h u m o r a l i m m u n e a c t i v a t i o e n c a w te o gor u l y d of o sc uc s tu ai r n ed u n d e r t h
s tres s .
Fu r t h e r s t u d i e u s s i n g u n i v e r s i t y s t u d e a n c a t d s e m f i a c c e i n i x g n a t i m o n s h ou ld con s id er
e x a m i n i n th g e T-re g s u b-p o p u l a t i an o n d th e s u pp res s ion or s h ift o f i mmu n e res p on s es in th e
f u n c t i o n a l m e a s u r e s ( b y m e a s u r i n g T t h o . k i 1 n e a n p d r o d T u h c . t i 2 o n c ) y t o e x p l o r e t h -e
s t r e s s
i n d u c e d e f f e c t o f n a t u r a l i s t -cells. i c s u s t a i n e d s t r e s s u p o n C D 4
Th ere was n o d if feren ce in C D 8 -c T e l l s ( C y -l t y m o t p h o c x y i t e s c ) p e r T c en t a g e s b e tween
th e S t r e s s and e d N o t -s t r e s s e s u d b g r o u p s, a n d t h i s is agai n c o n s i s t e n t with th e literatu re fin d in gs
s h owin g th at s t r e s s-i n d u c e d c h a n g e s i n t -cells h e is l in e con v e s il s ten s t [S o egers f tr C om D 8 & T
M i l l e r , 2 0 0 4 . ] T h ese i n c o n s i s t e n t r e s u lts m a y b e d u e t h t e o f a c t th at th e C D 8 -cel T l p op u lat ion P h . D . a t U n i v e r s i t y o f L o n d o n - 1 83 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
is n ot a h om o gen eou s en ti t y. Th e C D 8 -cell T p op u lat ion con s is ts of th ou s an d s of s p ecific C D8
T-c e l l s m a d e f o r a s p e c , i an f d i it c takes a n t mu i g ch e n lon ger p e riod to m a k e a s p ecific im mu n e
r e s p o n s e than a n i n n at e i mmu n e res p on s e. Hen ce, in con s is ten t res u lts ma y b e b ecau s e th e en d
r e s u l t s o f c o m b i n a t i o n s o f v iou a r s ch an ge s i n t h e h e t e r o g e n e o u s -cells e n t we i re t y o f t h e
s h o w n a n d b e c a u s e t e h t i m e p e r i o d w a s s h o e e r d t e e d r t o t h s a h n o w n a n y c h s a n g i e n u mb ers .
F u ture i n v e s t i g s a t o f i o s n t r e -i s s n d u c e d c h a n g e s -cell, i n i f an t y, h e s h ou C lD d 8 take T th is h e t e r o g e n e o u s f e a t u r e o f -c e l l t p o h p e u l a t i C o D n 8 i n t o T a c c o u n t, s o s h ou ld u s e a s p eci fi c
a n t i g e n t o s t i m u l a -c t e e l l a s u b t s , y p refe e
c rab i f l y i in c omb C D in 8 at ion T with fu n ction al
examin at i on s (p r ol i fe rat i ve res p on s es or c yto kin e p rod u ct ion s ).
4 . 1 . 2 T h e i n f l u e n c e o f p s yc h o l o g i c a l i n t e r v e n t i o n u p o n im m u n e p a r a m e t e r u s n ivers i n it y
s t u d e n t s
Alth ou gh th e su b ject n u mb ers d ecreas ed b y t h e t i m e o f n d t sh et e of s acad e c o emi c
e x inations a m l e a v i n g a t o t s tu a l d en o ts f , f 3 o 5 r t u n a t e h e l y we y re d is tri b u ted al mos t even l y
acros s th e t h r e e g r o u s p . T h e f i n d i n g s i n d ic a t e d t h a t th e R elaxation c on trol gr ou p s howed a
s i m i l a r t r e n d t o t h e s t r e s s e d i n d i v id u a l s i n t h e r a t l u r i e t a e t e xa m ti m e, i .e . th e tren d to d ecreas e
N K -c e l l p e r c e n t a g ; e s a n d t h is a t w a s t al h tered p a r t i c u l a r l y i n t h e J [ o h 3 r . e 1 i . : Figu 3 . g r 2 re o u p
2 6 ]. B a s e l i n e N K c yt o t o x i c a c t i v i t y r e s u l ts e w r e mis s ed d u e to th e d evel op men t an d ad ju s tmen t
of th e G o d o y -R a m i r e z ’ s a s s e s s m e n t s o m th e t at h an o d al ys es of th e e ffects of in terv en tion u p on
th e NK c yt ot o xi c act i vi t y were n ot p os s ib le to as s es s . Hen ce th e foll owin g s ecti on s d is cu s s th e
res u lts of th e N K -cel l an d l y m p h o c y t e d i s t r i b u t i o n s l y i n e a c h g . r o u p
R e l a x a t i c o n n t r o l g r o u p
The r e l a x a t c on i o trol n gr ou p at acad emi c e x a time m s h ow ed s imi lar d e c r e a s e s in N K -c e l l
l e v e l s to p u b li s h ed rep ort s ab ou t h i g h s t r e in s s d ividu e d al s [ B o r e l l a e t a l . , 1 9 9 9 ; G r u z e l i e r , S m
e t a l . , 2 0 0 1 ; -S I a n k o u r a e i e t a l . , 2 0 0 0 ; M a e s e t a l . , 1 9 9 2 ; S e g e r s t r o m & M i l l e . r Howe , 2 0 0 ver 4 ] ,
in ord er t o ma ke t h e o b t a i n e d c h a n g s e s t a t i s t i c a l l y t, s th i e g sn ai mp f i le c sa in ze cal c u lat ion s h ows
th at th e s u b ject nu mb er n eed s more th an 3 9 . T h e n u m b e r o f s u b ject s was on l y 11 , s o d efin itive
c o n c l u s i o n s f r o m t h e s e f i n d i n g s c a n n o . t Th is b e fi nm da in d g e ma y b e d u e to th e f o l l o w g i n
p o s s i b i l i t i e s :
1 . E x a m st r e s s d i d n o t s i g n if i c a n t l y -c e l l c l e v h e l a s ; n g e N K
2 . T h e s a m p l e s i z e sw mall a s t t o o do et ect t h e ch an ge; o r
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 84 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
3 . T h e r e l a x a t i o n , p r o v i d e d b y t h -f e e e m d o b c a k c k n e p u r o o c e d u r e a s p revi s h o ou w sn l y
[ E g n e r e t a l . , 2 0 0 , 2 its ] elf on l y or wi th at ten ti on given t o th e s tu d en ts (i.e. p laceb o
effect) m i g h t h a v e b u f f t h e e r e s d t r e -i s s n d u c -c e d l l creas d N e K e.
In ord er t o d et er mi n e t h es e h yp oth es es , a s s tated p reviou s l y, fu tu re in ves tigati on s h ou ld
h a v e a n i n t e r v -free e n t i c on o n trol g rou p a s wel l as th e R elaxati on con tr ol g rou p .
Self-h y p n o s i s g r o u p
In th e p r e v i o u s r e p o r ts i n t h e l i t , e r s e a l t f-h u r yp e n o s i s t rai n in g an d p ractice were s h own to
- +
b u f f e r t h e s t r -i e s n s d u c e d d e c l i n l e v e l in s e i t h e r N K -c e l l l e v e ls ( l a b e l l e d C a s D 5 6 C D or/ 3 an d
C D 1 6 + ) [ B a k k e e t a l . , 2 0 0 2 o ] r C D8 T-c e l l c o u n ts [ G r u z e l i e r , L e v y e t a l . , 2 0 , 0 o 1 r ] in b ot h NK
c e l l s a n -cells d C [ D G 8 r u z e T l i e r , S m i t h e t a l . , 2 0 0 w 1 he ] r e a s n -in o n ter ven ti on c on trol s s h owed
a s i g n i f i c a n t d . e c Th l i e n e elf-h S yp n os is g rou p i n t h e c u r r e n t s h o s w t e u d y n o c h a n g es in th e
N K -cel ls l e v e l s a t acad e mi c e x s a . Ho m w e v e r, it is a l s p o s s i b l e t h a t th e n u mb er of s u b jects was
t o o s m a l l t o d e t e c t di f f e r e n s; c e o r t h a t s t r e s -i s n d u c e d c h a n g e s i n t h e N -cells K w ere can cel led as
a r e s u l t o f a l t e r a t i p o r n i m o a f r y t a p h p e r a i s a l fro m s tres s fu l t o ‘n e u t r a l .’ In c o n tras t, C D 8 -cell T
levels w e r e creas i n ed in t h e elf-h S y p n o s i s g r o as u p s h own p revi ou s l y [ Gru zelier, Le v y et al .,
2 0 0 1 ] al th ou gh th e c h a n g e d l e v e l s o f -cells t we h e re n ot C D rel 8 at ed T to th e s tres s p ercep tion in
t h i s s t [3 u .1 d y .2 .2].
He n c e , i t w a s c o n c l u d e d t h a t t h i s s tu d y p a r t i a l l y s u p p o r s t t h e h y p o t h e s i s t h a t S -e
l f
h y p n o s i s m a y h a v e a c t e d a s s t -b r u e f s s f e r i f n o g r u n i v e r s i t y s t u d e n f t s a c i n g s a , c a d e m i c e
t h e r e f o r e , it w o u l d b e w o r t h e x a m i n i n g i t f u r t h e r i n g a r e a s t e u r d y n u m u s b i e n r g o f a s u b j , e c t s
a n d w i t h m e a s u r e m e n t s o f f u -c n c e t l i l o s n , a l i . a e c -cell . t i a ct c v i y vi t t y o y t o t a o x f i c C D T 8 T
s p ecific an ti gen , u s in g a d is eas ed p op u lation in wh ich th e a n t i g ( e s n ) c a n b e s p e c as i f i e d
p rop os ed ab ove.
J o h r e i g r o u p
I n t e r e s g l t y, i th n e r e s u l t f r o m t h e d c y u sr h owed r e n t th at s t th u e level s of N K -c e l l
p ercen tage in th e J oh rei g r o u p w e r in e cre as ed at acad emi c e xams . Alth ou gh th e a mp litu d es of
t h i s i n c r e w a s e e r e r e l a t i v e l y s m a l l an d al l p ercen tages an d cou n ts were with in th e n o r m a l ra n g e
[ H a n n e t e t a l . , 1 9 9 , 2 e ] i g h t o f e l e v e n J o h r e i p a r t i c i w p e a d n t r a s i s e d s h p o e r c e n ta g e s -cells o f N K
i n t h e i r p e r i p h e . r Th a l is tren b l d o o was d s ign ifi can tl y d iffe ren t f r th o at m of th e R el axat ion co n t r l o an d the Self-h yp n os is g r o u p s; a n d t h e e x p e c t e d d i -cells
r e c t i o n i
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 85 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
b a s e d o n t h e o b s e r v a t i o n o f s t r e s oth s e d in i th n e d cu i v rren i d t u sa tl u ds y an b d in th e literatu re
was o p p o s i t e t o t h a t o t f h e J o h r e i g r o u p i n t h e c [ u r 3 . r e 1 . n ]. t 3 . 2 s t u d y
A s d e s c r i b e d i n t h e i n t r o d u c t i o n [ 1 . 2 . 4 . 2 c u t a n e d s t 1 r . e s 2 s . i 4 s . 3 k ] n , o w a n i n t c o r e a s th e e
l e v e l s o f N K -cel l p ercen tag es an d N K c y t to o xic act i vi t y [ D o p p e t a l . , 2 0 0 0 wh ] ile s u s tai n ed
s tres s is kn own to d ec reas e th e le vels . Bo rella et al . [1 9 9 9 ] r e p o r t e d at s t h u d e n t s wh o are
e m o t i o n a l l y s t a b l e i n p e r s o n a l i t y p r o f i s l e e d h N a K v e c i y n t c r o e t a o x i c a c t i g v th i eir t y d u r i n
acad emi c e x s. a Fu m r t h e r , i n t h e o t h e r n o t-d is eas ed p op u lation , D e G u c h t e t a l . orted a l s o r e p
[1 9 9 9 ] t h at su s t ai n ed s t res s i n creas ed N K -c ell cou n t in th e gr ou p with h igh p rofes s ion al s t r e s s�
( m e a s u r e d b y t h e N u r s e S t r e s s I n d e x b) u t l o w p s y c h o p a t h o l (th o g os y e wh o h ave g ood ad ap tive c o p i n g a b i l i t i e s t o t h e i r s y m p t o . m Th s ) e s e f i n d i n g s a n d t h e u lts r e s from th e cu r ren t s tu d y
s u gges t ed t h e p os s i b i l i t y t h at J oh rei ma y h ave i n c r e a s ed t h e em otion al s tab ilit y or d ecreas e
p ath ologi cal i mp act o f s t r e s s . F u t u r e r e s e a r c h s o n J o h r
s h o u l d e m p l o y a l a r g e r s a m p meas l e us res i z oe f p w e r i -N t K h -c e l l c y t o t o x i c lev a c els t i in v i t y
ord er t o c on fi rm t h i s fi n d i n g.
Des p ite th e limitations, it is, n e verth eles s , con clu d ed th at th e p s y c h o l o g i c a l i n t e s, r v e n t i o n
p a r t i c u l a r l y oh J rei, ap p eared to h a v e p os s ib le b u fferin g or even c o u n t e r a c t in g e f f e c ts of
examin at ion s tr es s u p on the d i s t r i b u t -cells i o , n a n d/or o f C D 8 -cells t T h , e in th N e K u n ivers it y
s t u d e ts. n
4 . 1 . T 3 h e i n f l u e n c e o f p s y c h o l o g i c a l is i ea n t s e pr rog v e res n t s i ion o n ma u rp ker o n ( CD4 d T
c e l l c o u n t ) a n d s t r e s s-rel a te d perce pti o n in H I V-i n f e c t e d i n d i v i d u a l s
T h e h u m a n i m m d u e n f o i c i e n viru c y s ( HI V), a l e n t i v i r u s o f a s u b g r o u p -vir o f ur s es e t , r o
p r o g r es s i vel y d es tr o ys th e i mmu n e cells, C D -cells 4 T i n p a r t i c u l , a r a n d t h i s to l th e a life- d
t h r e a t e n i n g d i s e e, a s t h ac e q u i r e d i m m u n o d e f i c s yn i e dn ro c me y (A I D S), a n d d e a . Th t h e d ecl in e
o f C D -cells 4 T is kn o wn to b e a s s o c i a t d e with a r i s k o f d e v e l ing o p op p ort u n is ti c infect ion s s u ch
a s P n e u m o c y s t i s c a r in i i p n e u m o n i a o r o e s o p h a g e a l c a n d i d i a a s i s s w e l l a t s h r e i s k o f d e v e l o p i n g
t u m o u r s, p a r t i c u l a r l y th o s e r e l a t e d t o i m m u n e s u p p r e s s i o n , s u t c h Ke ap a s o s i ’s sarco ma or
N o n -H o d g k i n s l y m p h o m . a
Hen ce, H I V i n f e c t i o n m a y b e c o n s i d e r e d t -lon o b g e b ia ol ol gi i cal f e an d p s ych ol og ical
s t r e s s o r, a n d i t i s k n o w n t h a t s t r e s s l e v e l s c o n t r i b u te t d o e t r i m e n t a l e s a o s u s o t c i c a t o e d m w i t h
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P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
HIV d i s e a s e p r o g r e [C s s atalan i o n et al ., 1 9 9 5 ; C ol e et al., 2 0 0 3 ; C ole et al., 1 9 9 7 ; C ole et al. ,
1 9 9 6 ] . Th e c u r r e n t p r o j e c t a i m e d t o d e l c r e a s v e e t l h e o f s -i t n f r e c e t s e d s i n ud als i v n i d t h e H I
s o th at t h ei r d i s eas e p rog res s ion can b e d e l a ye d , all owin g th es e in d ivid u al s to mai n tain th ei r
h e a l t h a n d w e l l-b e i n g an d d ela y th e req u iremen t to co mm en ce an ti ret r ovir al d ru g t h erap y an d it s
i n h e r e n t c o m p l i c a t i . o n s
4 .1 . 3. 1 Di s eas e p rog res s ion ma rke r a n d s t r e s -r s e l a t e d p e -i r n f c e c e t e p d t i n i d i v o i n d u a l s i n H I V
C D 4 -c T e l l c o u n ts i n -i H n f I e c V t e d i n d i v i d u a l s , a m a j o r c l i n i c a l p a r a m fo e r t e mr on it ori n g
d i s e a s e p r o g r e s s i o n , i d s e c l k i n o n w e n o v t e r o t h e c o u r s e o f -l t o h n i g s i l n i f e c [d t e i Wol o n f et
a l . , 1 9 9 7 . ] A s t e a d y d e c l i n e i T-c n e l l C c D o 4 u n t s o f 7 ± 3 c pe er l l s l p er m o n t h o ver a 1 2
m o n t hs p e r i p o r d i o r t o t h e i r e n r o l m e n t i n t o t h e s th t e u tot d y al w of a s 9 5 H o b I s e V- r v e d i n
i n f e c t i e n d i v i d u a l s [3 .2 .3 .1 ]. Similarl y, H I V-in fected i n d i v i d u a l s wh o are n ot rec eivin g an y
a n t i -r e t r o v i r a l t r e a t m e n ts in ou r w a i t -listed c o n t r o l g r o s u h p o w e d a d e c l i n e -cell i cn ou n tC s D 4 T
o f 1 2 ± 1 7 c e pl er l s l p er m o n t h o ver a f i v -m e o n t h p e r i [ 3 o . d 2 . 2 . 2 . ] T h e s e w e r w e i t h i n t h e
av e r a g e r a n g e o f p u b l i s h e d f i n d i (8 n g s to 1 6 c e l l ps er l p er m on th ) [ d e W l f o e t a l . , 1 9 9 . 7 In ]
t h e c u r r e n t p r o j e c t , t h i s r a t e -cells o f was d a n e a c l y l sed i n e ord er i tn o t h e n u m b e r
d e t e r m i n e i f s t r e s s p e r c e p t i o n h s a with s a tn hy is rat a s e s of o c di ecl a t in i e. o n
Th e res u l t s in t h e H I V-i n fected i n d i v i d u a l s s h owed th at o b s e r v a t i o n a l s in gle time p oin t
m e a s u r e m e n t s o f p e r c e i v e d s t r e -o s s f -life , q a u n a d l si leep t y q u al it y d id n ot c o r r e l a t with e th e rat e
o f c h a n g e i n -c e l t l h c e o u n , C t i.e. s D 4 s cores T at on e s in gl e tim e p o i n t d id n ot p r e d i c t or
i n d i c a t e h e r a t e o f c h a n g e i C n D t 4 h -c e e T l l c o u n . t s I n a d d i t i o n , t h e levels c h a n ove g e r th e
s tu d y p eri od in th e P e r c e i v e d S t r e s s S c a l e ( P S S als ) o d i d n o t c o r r e l a t e wi th th e rate of d eclin e.
Howev er, th e res u lt s d i d t h s a t h d e o c r w e a s es ove r a f o u r -m o n t h p e r i o d t h i s e n e n s e o f t a k i n g
co n t rol o f o ’s n e o w n l i o r f e i n n e r-p e r s o n a l c o p i n g a ( LoC b i l ), i p t s y c h o l o g i c a l f u n c t i o n i n g
( M C S ) a n d s l e e p q u a l i t y ( P S Q we I ) r e s t r o n g l y c o r r e l a t de e c d l i w n i e in t h t h e
c o u n t s [ 3 . 2 . 1 . 2 . ]
C D 4 -cell T
T h e s e f i n gs d i m n a y i m p l y t h e p o s s i b i l i t y t h l a e t v e ls c h a f o n au g e ton o m y o r at ti tu d es of
a c t i v e l y b e i n g e n g a g e d i n t , h as e i op r p os l i ed f e to meas u res of p as s ivel y e xp erien c ed s tres s
(s tres s p ercep ti on ), ma y b e a s s o c i a t d e w i t h t h e r a t e o f c h a -c n e g e l l i n c t o -h
u e n t C D 4 i T n H I
i n f e c t e d i n d i v i d u . a T l h s i s p o s s ib i l i t y is c o n s is ten t with th e s u gges tion in th e Wh iteh all Stu d y II
[ B o s m a e t a l . , 1 9 9 8 th ] at ‘s e l f -e m p o w e r me n t ’ m ay h a ve b en eficial effe cts o n t a c k l di is n eas g e
p h ys iol o gi cal l y. Fo r t h e p u rp os e of e xa mi n in g th is h yp oth es i s th at an in creas e of th e s en s e of
‘s e l f -e m p o w e r m e n t ’ imp rov es ( d e l a s) y d i s e a s e p r o g r in e s s i H o I -i n V n f e c t i o n o r m a i n t a ,
i n s h e a l t h
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 87 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
th e S e n s e o f C o h c e r e (SoC) n [ A n t o n o v s k y , 1 9 8 7 ] ma y b e a go od d om ain to as s es s in f u t u r e
s t u d i e s, b ecau s e t h e S o C i s d e s i g n e d t o m e a e s u a r p o s i t i v e i n n -p e r ers on al coh eren c e wh ich con s is ts of th e le vel s o f c omp reh en s ib ility, man ageab ilit y an d mean in gfu ln es s [ 1 . 2 . 3 . 2 . ]
I n c o n t r a s t t o t h e -c a ell n a cou l ny ts s , ti h ere s was o f n o t ren h d e in th C e D level 4 T s of th e
H I V v i r a l -c e l l o o u c n a t s d i o n -i r n f e H c I t N e d K V i n d i v i d u a l s ( n o t r e c e i v i n g a n t i-r e trovi ral
t r e a t m e n t ) a cros s t h e five m o n t h s p e r i o d w i t h r e g a r d t o e i t h e r t h e C D 4 g r a d i e n t o r t h e evels l o f
th e p ercei ved s tres s , q u a l -o i t f -li y fe o r s l e e q p u a l i [ 3 t . y 2 . 1 . 2 ]. T h e l e v e l s o f H I V a r v e i r a l l o a d
clin ical l y u s ed to m on it or d i s e a s e p r o g r e s s i o n i n c o m b i n a t i -cell o n w i t h t h e
c o u n t s , a t n d h e ay re u s e d to e x a m i n e t h e r e s p o n s e ti-ret t o ro vi a ral n t reat m en ts , s o t h e viral l oad
levels mi gh t n ot b e a s u i t a b l e o u t c o m e m e a s u r e f o r s t u d su y b j e cts wh o are n ot rece ivin g a n t i -
retro viral t r e a t m e n t . S i -c m i e l l s a r a r l e y k n , o w p l n a an y t l o imp t ort h an o t u rol g e h in N K
d e f e n s i v e m e c h a n i i n f s e c m t s i o n p a r a o n g d r a e i s s n i [F o s a u t c i e t H a I l . , V 2 0 0 , 5 n] o con s is ten t
tren d wa s f o u n d b e t w e e -c n e l l t s h a n e d d n i s u e m a s b e e p r o g H r I o e s f V-i s n i f o ect N n ed K i n
i n d i v i d u a l s, s -c o e l l l e N v K e ls m i g h t a l s n o t b e a s u i t a b l e o u t c o m e m e a s u r e f o r u s t b u j d e y cts. s
C o l l e c t i v e l y, it can b e c o n c l u d e d t h a t t h e r a t -cell e c ou o f n t (C d D4 e c l i n e i n C D 4
g r a d i e n t ) in treat men t n a ï v e H I -in V fected p at ien ts is an imp ortan t an d u s efu l p ractical o u t c o m e
meas u remen t f or th e in ves ti gati on of th e effect of p s y c h o l o g i c l a in ter ven ti on u p on d i s eas e
p rogres s i on . N o t a b l y, it i s a l s o d e m o n s t r a te d t h a t t h e c h a n g e l e v e l s p o e f r c e i v e d q u a -o l f -life, i t y
w h i c h can b e i n t e r p r e t e d a s t h e attitude c h a n of g e act i vel n y b e i n g e n g a g e d i n t h e i life r an d / or
t h e c h a n g e i n s t e h n e s e o f m e a n i n g f u l n , e s m s a y h a v e d i re ct as s oci at i on s with this c h a n g e th i e n
C D4 T-c e l l c o -p u a t n i e t n t . s A c i cor n d in gl H y, I i V m p r o v e m e n t o f t h e -f m ocu e a sn ed i n cop g in g
skills [ 1 . 2 . 3 . 2 ] m a y h a v e b e n e f i c i a l e f f e c t a s n d u w p e o l n l-b e h i e a n g, l an t d h th erefo re it can b e
o f g r e a t i n t e r e s t f o r t h e ect e f f of p s ych ol o gi cal in ter ven tion .
4 .1. 3. 2 Th e i n f l u e n e c of p s ych ol ogi cal in terven ti on u p on C D 4 -c T e l l s a s di a s e a s e p r e o s g s i o n
m a r k e r i -i n f e c t t e d h i n e d i v i H d I u a l V s
T h e r e s u l t s s h o w e d t h a t, in all th ree g rou p s , t h e r e w a s a s t e a d y d -cell e c l i n e i n t h
c o u n t s b e f o r e t h e s t u d y c o a m n m d e n c t e d h e a b s -c o e l l u c t o u e n t s C w D e 4 r e s i T m i l a r [ 3 . 2 . 3 . 2 ]
Aft er c om men cemen t , th is d e c l i n e o -cells f C c D o n 4 t i T n u e in d c o n t r o l s (t h e w a i t -l i s t con e d trol s
in th e fi ve mon th s s tu d y [3 .2 .2 .2: F i g u r ] e an 4 d 0 th e Dat ab as e con trol s in th e 2 4 mon th s s tu d y
[ 3 . 2 . : 3 . 2 F i g u r ]) e . T 4 h 4 e o n-t r e a t m e n t a n a l y s i h s o w e d t h a t this d e c l i n e r a t e o -cells f C D 4 T
was s top p ed , an d even reve rs ed , in th e H I V-i n f e c t i e n d i v i d u a l s fo l l o w i n g J o h r e i an t r d a i n i n g
p r a c t i c e o v e r t h e f i v e m wh o n ile t h t s h e p r e r i w o a s d n h o a n c g e in t h e elf-h S y p n o s i s g r o u . p Th is
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 88 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
i n t e r e s t i n g d i f f e r s e h n o t w n t r b y e n d t h -t e r e a o t n m e n t a n a l y s i s n t h e f i v e m o n , t hh owe s ver s t , u d y
w a s n o t c o n f i r m e d b y t h -t e o-t I r n e t a t e n a t n i a l o y n s i u s g g e s t i n g t h a t uf tu re s t u ies d exami n in g
this e f f e c t o f J o h r e i will r e q u i r e a l a r g e r s a m p l e s i z e ( m o r e t h a n 8 4 s u b j e c t s p e r e a c h g r o u p )
[ 3 . 2 . : 2 . 2 T a b l e ]. 3 9
Th e red u ct i on i n t h e d ecl i n e of th e C D4 T-cells in th e in d i vid u al s in th e J oh rei gro u p m a y
h a v e c o n t r i b u t be oth d pt so ych ol o gi cal a n d p h y s i o ical l o g s tr es s red u ct ion . In ad d it ion to
imp ro vi n g i n d i v i d u a l ’s w e l l -b e i n g, th ere i s b oth an in d ivid u al and econ omic b en efi t in th at an y
red u cti on i n t h e s p eed of d eclin e of C D4 T-cell c ou n ts will effecti vel y d el a y th e ti me wh en an
i n d i v i d u a l p a t i en t w il l m e n c e o e m x p e n s i v a e n t i-r e t r o v i r a l tr e a t m e n t s. Th is will on l y b e d ela yed
r a t h e r t h a n a , v o i b d u e t d m a y h e l p t o k f e r e o p m a a w a v y i c i o u s o c i f r s c t l r e -in s s d u ced
d etrimen tal ch an ges towa rd s a c c e l e r a t i o n o f t h e d i s c e a s s e towa p r rd o s AIDS an d wi ll d ela y
e x p o s u r e t o t h e t o x i c s i d e e f f e c t s o f a n t i-r e t r o v i r a l d r u . g s
Li mitat ion s h ou ld al s o b e men tion ed . R e c r u i t ing a n d m o t i v a t in g p a r t i c i p a n for t s a
r a n d o m i s e d c o n t r o l l e d t r i a l ( R C is T ) kn o wn to b e ch al len gi n g. W a l k e r s u g g e s t e d i n h
t h a t p erfor mi n g e x p l a n a t o ry an d p ragmati c R C Ts can min imis e th es e p rob lems [ W alker &
A n d e r s o n , 1 9 9 9 ]. I n f a c t , t h e u n i v e r s i t y s t u d e n t s t u d y -ou d i t d rat e n o ut p u nh ta il v e a h i g h d r o p
th e time t h e t rai n i n g s es s i on s were co mp leted . Th is ma y b e d u e to th e fact th at th e cu rren t s tu d y
u s i n g u n i v e r s i t y u s d e n t s e m p l o y e d t h e m o -fe c k ed bn ack e u r so es s ion s as a c on trol con d ition ,
wh ich i s s i mi l ar t o exp l an at or y an d p rag matic trial s in ce th e s ame a mou n t o f ca re an d atten tion
w a s g i v e n t o t h e c o n t r o l i n d i v i d u a l s . in th O e n HIV t h se tu do y, t h th e r c on h a tr n ol d g rou p
s u b j e c t s w e r e r a n d o m l y a s s i g n e d a n d h a d t o w a i t f o r f o u r -ou m t o rn at t e h s , a n d h a d h i g
c o m p a r e d w i t h t h e S e -h l f yp n os is an d J oh rei g rou p s .
F u r t h e r , lth ou a gh th e s tu d y s u b ject s were ran d oml y as s ign ed to th e th ree gr ou p s , actu al
n u m b e r s f o r an t h al e ys es were d if feren t a n d th e nu mb er in th e J oh rei gr ou p was th e s malles t in
t h e -p atien H I t V s tu d y. Th is was n ot a s s o c i a t e d w t i h t e h d -ou r o t p rat e b u t b ecau s e th e n u mb er of
s u b j e c t s w h o w e r e a s s i g n e d t o t h e g r o u p b u t d id n o t t u r n a r o u n d t h e f i r s t t r a i n ni g s es s ion was
th e larges t i n t h e J oh rei gr ou p . It ma y h a v e reflect ed s ome p s ych olo gical d iffi cu lties in t r yin g a
n o v e l ( o r e v e n s t r a n g e l y s o u n d i n g ) p r o c e d u r e l i k e J o h r e i . T h i s m a y h a v e r e s u l t e d -i
n a s e l f
s e l e c t i w o n i t h i n t h e J o h r e t i o w g a r o d u s p a p lar a r pt ers i on c u al it y t yp e, e.g . op en m in d edn es s or
n ovelt y s e eki n g in th e T e m p e r a m e n t a n d C h a r a c t e r (TC I n v I) e n [ C t l o r n y i n g e r e t a l . , 1 9 9 . 3 ]
Th is p ers on al i t y fact or s h ou ld b e exa min ed in fu tu re in ves tigation .
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 89 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Co m p l i a n c e o f u s i n g p r o c e d u r e a f t fo e r th e t sh te u d y t pr eri a i od n i was n g s imila r b etween
J o h r e i a n d S e l -h f yp n os is , b u t wi th regard to coll ection of t h e d a t i a n t h -p e a t i e H n I t I s , V t u d y
p a r t i c i p a n t s i n t h e S -h e l yp f n os is gr ou p at ten d ed more s amp le c ollecti on time p oin ts . Th e
a p p o i n t m e n t s f o r t h -c e o l d l a e t c a t i o n s e s s i o n s i n b o t h S -h e l yp f n os is an d J oh rei gr ou p s were
m a d e b y t h e s a m e r e s e a r c h a s s i s t a n t (Mr. B . B e n n e t t wh ) o h ad at ten d ed b ot h in terv en tion
s e s s i o n s . He n c e , th i s m a y i n d i c a t e t h a t i n d i v i d u a l s i n t h -h e yp S e nl f os is gr ou p were mo re
c o m m i t t e d t o t h or e b e s n t e u f d i y t d e m o r e f r o m c o n t a c ts wi th the s t u d y r p s e o n e l (Dr. T .
L a i d et l al. a ) w t h a n t h e J o h r e i p art icip an ts , reme mb erin g th at J oh rei , f or th e m os t p art , was
p erfor med wi th a p art n er. N o n e t h e l e s s , a n e cau x t r ti a on s h ou ld b e gi ven wh en th e p s ych ol ogical
effect fr om t h e res u l t was d i s cu s s ed . On e p roced u re to ov erc ome th i s b ias i s to u s e th e meth od
of t h e I n t e n -t t o-treat i o n an al ys is as ap p li ed in th e cu rren t s tu d y.
Al t h o u g h t h e r e r limitations, e m a i n t h e s e i n v i v s o t u d i e s d e m o n s t t h a r t : a t e d
A c a d e m i c e x a m i n s a t i c a o i n
n d u c e s t r e s s i n u n i v e r s i t y s t u d e n ts [ 3 . 1 . 1 . 1 ; ]
N K -c e l l f u n c t i o n a p p e a r e d t o b te e d a wit s s o h c si ta res s p ercep ti on in u n ivers it y
s t u d e n t s [ 3 . 1 . 2 . 1 ; ]
P s y c h o l o g i c a l i n t e r v e n t i -s t o r e n s s-i n d um ced a y c o u n t e r
l o s s -c e o l l f p e r c N e n K t a g e i n u n i v e r s i t y s t [ u 3 d . e 1 n . t 3 s . 1 : F i g u r e 2 ; 6 ]
P s yc h o l o g i c a l i n t e r v e n t i o n , p a r t i c u l a r ly J oh rei, ma y s l ow th e d is eas e p ro gres s ion i n
H I V-i n f e c t e d p a t i e n [ t 3 s . 2 . 3 . 2 : F i g u r e 4 ; 3 a ] n d
I m p r o v e d p e r c e i v e q d u a l -o i t f -life y s c o r e s a r e n e g a t i v e l y a s s do is c i eas a t e e d w i t h
p r o g r e s s -i i n f o e c n t e d p i a t n i e n [ t 3 H s . 2 I . 1 V . 2 : T a b l e 3 , 0 an ] d J oh rei ap p eared to i m p r o v e p e r c e i v e d -o q f u -l a l i f i e t s y c o r e s [ 3 . 2 . 2 . 1 : T a -3 b 7 l ] . e s 3 5
Th e s e f i n d i n g s u pp ort th e h yp ot h es is th a t p s ych ol ogi cal in terv en tion m a y alle viat e th e
d etrimen tal effe ct s of s tres s u p o n w e l l -b e i n g; a n w d a r r a n t t h e n e e d o f f u r t h in e r ves ti gat ion on
the ps y c h o-n e u r o-e n d o c r i n -i o m mu n e n et wor k, p a r t i c u l th a r e l in y fl u en ce of J oh rei u p on th e
n e t w o r .
k
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 90 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
4 .2 S t r e s s h o r m o n e a s s o c i a te d c ha ng e s i n v i t i r i mmune o n c e ll s a s a n e x e m p l a r o f
the p s y c h o-n e u r o-e n d o c r i n -i o m m u n e n e t w i o n r t k e r a c t i o n
Th e s t u d i e s u s u i n i n v g e r si t y s t u d -i e n f e t c t d s e p a t i e a n t s n d e m o n H s t I r a t V e d t h a t
p s y c h o l o g i c a l s t s r e as ffect ed in vi vo d i s t r i b u t i o n o f
i m m u n e c e l l -c s e l l i s n -cells. c a l n d u d T i n g N K
Th e r e h a s b e e n g r a o w i n g b o d y o f e v i d e n c e w h i c h s u g g e s t s t h a t c o r t p i s a o r t l i c ( u l a rly i n t e ract i on
with t h e g l u c o c o r t i c o i d t y p e r I I e c e p t o r ) m a y p n l i a m y p o a r t a n t r ol e in s t r e s -in s d u ced ch an ges
[ B a u e r e t a l . , 2 0 0 3 in ] b oth l ymp h oc yt e d is tri b u tion [ D h a b h a r e t a l . , 1 9 9 6 a ] n d i m p a i r e d c e l l-
med iat ed res p on s e [ B a u e r e t a l . , 2 0 0 . 1 ]
H e n c e , th e e f f e c t s o f s t r e s s h o r m o n o e s r t ( i c s o l i n p a r t i c u l a r ) im u mu p o n e t cel h e l s were
in ves ti gat ed i n v i t i r n o o r d e r t o e x a m i n e i f an t y h de r irect e a ir ne teract ion s b et wee n th e s t r e s s
h o r m o n e s a n d h ich i m c o m u l u d n f e u n c t c i o e n a l l y s d e m o w n a s t p r a a r t e o the f p s y c h -n o e u r o-
e n d o c r i n -im o mu n e n et work .
T h i s a p p r o a c h c o n s i s te d o f t w o s e r i e s o f e x p e r i m e n t s : ( 1 ) a n i n v e s t i o g a f t i o -c n N ells K an d
(2 ) a n a n a l y -cells s i s . Th o e f fu n ct T ion al p arameters in c e l l u l a r i ity m m [ R u o n s e , 2 0 0 2 ], wh ich w e r e r e p o r to t e d e c r e a se u n d e r s u s t a i n e d s t r , e s i s n c l u : d e
1 . Cy t o t o x i c a c t i o v i f t -c y e N l K l s a n d / o r -cells c y a gai t o n s t to arget x i c cel ls T (t u m ou r
cells an d vi ral l y i n f ect ed cel ls ) [ B orella e t al., 1 9 9 9 ; Gru zelier , Smith et al., 2 0 0 1 ;
I n o u e-S a k u r a i e t a l . , 2 0 0 0 ; M a e s e t a l . , 1 9 9 2 ; P i k e e t a l ; . an , d 1 9 9 7 ]
2. T-l y m p h o c y t e p r o l i f e r a t i v e r e s p o g n e s n , e s a s t u p o e r-an a ti gen m i t or o s p eci fic
an tigen s [ S i l b e r m a n e t a l . , 2 0 0 . 2 ]
Hen ce, in th is p roj ect , th e e ffect of i n v i t e x r p o s u r e t o t h e s t r e s s h o r m o n e ( c o r t i , s o in l )
t h e u p p e r p h y s i o l o g i vc els a l an l d e for m o re th an 2 4 h ou rs , u p on th e NK c yt ot oxic activit y a n d
t h e -l y T m p h o c y t e p r o l i f e r a t i v e r s e were s p o n is ne ves ti g at ed .
4 . 2 . Cha 1 ng es in NK-cells a fter in vitro i n c u b a t i o n
U s i n g p e r i p h e r a l b l o o d m o n o n u c l e a r c e l l s ( P B M C s ) , (N N K K C A c ) y lev t o el t o x i c a c t i v i t
was i n v e s t i g a t e d b y u s i n g t h e -R G a o m d i o y r e z ’ s f l o w c y t o m e t [G r y o d m o e y-R t ami h o d rez et al .,
2 0 0 0 ] t o o b t a i n a p i l o t r e s u l t , a n d t h e n e x a m i n e d b y u s n i g t h e C y t o T ® o x 9 wh 6 ich meas u res an
amou n t of r e l e a s ed L a c t a t e d e h y d r o g e n a s e ( L D H ) f ro m th e d ead cel ls . T hese tw o d ifferen t s ets
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 91 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
of res u lt s fro m th e tw o a l t e r n a t i v e t h m o e d s of me as u ri n g N K C A l e v e l pr s o v i d ed a mo re
c o m p r e h e n s i v e a c c o u n t.
4 . 2 . 1 . N 1 K c y t o t i o x c a c t i v i t y ( -c N e l K l C p A r ) o f i l ae l fter s e in v cu e b at l ion s o f Pa B MC n d s N K
for 2 4 ho u rs i n v i t r o
NKC A l evel s we re s h own t o i n c r e a s e a f t e r i n c u b a t i o n o f P B M C s f o r 2 4 h o u r s a n d t h i s
i n c r e a s e d l e v e l w a s s o c i a t e d w i t n c h r e a s n e d l e v e l s o f t h e p -N e r K -c e l l c yto t o x i c a c t bi uv t i t y
n o t t o a n i n c r e a -c s e l l e s u b si et [ n C o o p c e r y , F t e h o n i t g e r o & x i C a l c i g i u r N i , K 2 0 0 1 n ] um b e r s.
T o m i n i m i s e t h e p o s s i b i l i t y acti o f vat ion cau s ed b y an in teracti on b etween an tigen
p r e s e n t a t i o n -cells c e dl u ri l n g s th e 2( 4 hA ou P rs C i ) n v a i t n i r d n o c u b N a t K , i mon o n oc yt es w ere
r e m o v e d f r o m P B M C s b y c u l t u r i n g f o r 1 h o u . r P r i e n v i sa o l y, u p Nl KC a s t A i level c f wl as a s k
r e p o r t e d t o -c b e l l h s i u b s g e h t e a r d h e r i e d n t o t p l h a e s t i N c K f l -ad a s hk eren s t h a n i n t h e n o n
N K -c e l l s u b s e t w h e n -2 i , n c a u n b d a t h e s d e w t i w o t -s h ets N K exp I s L res u b s d iffe ren t
ch emoki n e recep tor p ro fi les [ I n n g j e r d i n g e n e t a l . , 2 0 0 . 1 ] T h e P B M C ps rep ared wi t h th is m o n o c y t e d e p l e t i o n p r o c e d u r h e a v s e h r o em u o l v d e d t h -c e l l N K s u b s e t a d h e r e d t o flas p l ks a s t i c
a s w e l l a s m o n o c yt e s , b u t p e r -N K -cell c ytoto xic acti vit y was in creas ed in th e cu rre n t s tu d y, s o
th is s u gges ts th at th ere were oth er f a c t o r s w h i c h c o n t r i b u t e t o t . h e i n c r e a s e
N K -cel ls are ri ch in t h e i r s u rf a c e r e c e p t o r w s h i c h c o n v e y in h ib it ion o r a c t i v a t i o n s i g n a ls
[ M i d d l e t o n e t a l . , 2 0 . 0 Th 2 ] e Nkp 4 6 i s n as k a n m o a i w n a c t i v a t i o n s i g n a l f or th e c ytoto xic
l y s i n g a c -cells, t i n v a m i e l t y t y h e N o a t f u r a l C N y K t o t o x i c R e c e p t o r ( N [Sp C R a) ggi ari et al . ,
2 0 0 1 ] , an d t h e exp res s i on of th is rec ep tor was s h own to in creas e afte r th e in cu b ation alth ou gh
t h e e x p r e s s i o n o f t h e o t h e r N C R , t h e N k p . 3 Hen 0 , ce, w a th s e in n creas o t ea d f lf evel e c t s e o f d th e
p e r -N K -cel l c yt ot o xi c a c t i v i t y a f t e r t h e i n c u b a t i o n c o u l d b e o n a c c o u n t o f :
1 . In cre as i n g t h i s Nkp 4 6 activation s ign als ; an d /or
2. De c r e a s i n g e f f e c t s o f i n h i b i t o r y p r o c e s bs y e oth s er o f u nt id h en e ti fi a ed c t i v a t i o n
f a c t o r s.
On e p o s s i b l e d e c r e a s i n g i n h i b i t o r y e f f e c t i s o val t of h en e d ogen r ou e s m h u moral
s u b s t a n c es ( s u c h a s s t r e s s h o r m o n e s p) rep i arat n t ion h e fo r i n v i in t cu r o b at ion . Th e p las ma
s ep arat ed fro m t h e P BMC s was r ep laced b y a cu ltu re med iu m with a o n e -tenth, lo w
c o n c e n t r a t i oetal o n Co al f S eru F m wh ic h con tain s little o r n l o e v e l s o f e n d o g e n ous cort is ol.
Th e h yp ot h es i s t h at t h i s rem ov al o f en d o gen ou s cortis ol cau s es th e activati on in th e levels of
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 92 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
p e r -N K -cel l c yt ot o xi c act i vi t y an d th e ex p res s ion of th e N kp 4 6 (an d Nkp 3 0 ) was in ves tigated in
th e foll owi n g exp eri men t s .
4. 2 . 1 . C 2 o r t i s o l -i n d u c e d c h a n g e s i -c n e l l p N r K o f C i A l e s l e v e l s a n d N K
C o r t i s o l w a s s h i o w n h n i b t i o t t h e i n c r e a s p e e r-N o f K t -c h e l l c y t o t o x i c aa ft c er t 2i 4v hi rs t y
i n c u b a t i o n o f P B M C s a n d this inh ib ition of th e i n c r e a s e was s h own to b e a s s o c i a t ed with an
i n h i b iti on of t h e e x p r e s s i o n o f th e N k p 4 6 ( a n d a l s o w i t h t h e o f i t n h h e i N b k i p t 3 0 i on ) o n th e
c y t o t o -cell x i s uc b s et s . N H K o w e v e r , t h e s e i n h i b i t i o n s o f t h e i n c r e a s e i n t h -N e K p -cell e r
c y t o t o x i c a c t i v i t y w e r e n o t f u l l y a c h i e v e d ir i n a t m e r p m l s i o f t u h e d an e d Nkp o 4f 6 N K C A
e x p r e s s i o n . T h i s a g a i imp n lies th at th ere m a y b e o t h e r c on trib u tin g facto rs .
R ecen tl y, i n v i s v t o u d i e s u s i n g m i c e ( c . f . g l u c o c o r q t u i c v o a i l e d n t i h or s mon t h e ie n mi ce
to co rti s ol in h u man ) h ave s h own th at glu coco rticoid r e s i s t a n c e c a n u c b e d i b sn y ocial d
d is ru p ti on s t res s (i .e. rep et i t ive d is ru p tion s b y in s ertin g in tru d ers in to a ca ge to s tre s s mice)
[ A v i t s u r e t a l . , 2 0 0 1 ; Q u a n e t a l . , . 2 0 0 T 1 h ] i s g l u c o c o r t i c o i d r e s i s t a n c e b e w a s r e p o r t e d t o
a s s o c i a t d e w i t h t h e e r d u c e d f u n c t in i o the n gl u coc ort ic oi d recep to r in th e C D 1 1 b pos itive
m a c r o p h a g e s ( i . e . o n e o f m a j o r a n t i g e n p r e s e n t a t ; i C o D n 1 c 1 e b l l i s p a r t o f t h e ’ c e l l s
i n t r a c e l l u l a r a d h e s i o n m o l e c u l e s w h i c h a r e e x p ) r in e as s s oci e d at u io p n o n wi ta h c t h ei i r v a t i o n
i m p a i r e d n u c l e a r an t r s locat i on of gl u coc o rt icoi d recep t or an d th e lack o f tran s crip ti on al
s u p p r e s s i o n -k B o f b y g N l F u c o c o r t i c w o h i e d n -cells N K in ter act wi th th e ma crop h ages [Qu an et
a l . , 2 0 0 3 . ] It is th eref ore s u g ges ted th at m o n o c y t e d ep letion cau s e a re mo val of th e C D1 1 b
p os itive ma crop h ages res u lt in g in a d ecre as e in th e i n h i b i t o r y p r o c e s s e s o f t . h e a c t i v a t i o n
It i s w e l l-k n o w n t h a h t a r m p a c o l o g i c a l le v el s of c ortis ol af fect gen omi c man ifes tati on s in
N K -c e l l s , f o r e x a m p l e , t h e ol f e th v e l G s r a n z y (a m maj e or A c yt ot o xi c mol ecu le c on tain ed in
t h e cy t o p o l f a N -c K s e l l m s) h a v e b e e n re p o r t e d t o b e -cells r were e d exp u c os ed e d to w h e n N K
t h r e e M of c ort is ol [ Z h o u e t a l . , 1 9 9 . 7 ] H o w e v e r , t h e r e a i l s s a o g r o w i n g b o d y id o f en ce e v
wh ich h as d e m o n s t r te a d t h a t t h e r e a l r s e o n -g n e n o m i c c o r t i s o l e f f e c s t u s c h a s i t r h e c t d -n
o n
s p e c i f i c n o n-g e n o m i c s t e r o i d th a rc ou t gh i o h n i g h-a f f i n i m t e y m b r a n e-b i n d i n g s i t , e i.e. s c ort is ol
c a n a f f e c t t h e a -k c B t via i v s i t e y r o -m i o d e f m b r N a F n e i n r t a c e t i o n s w i t h o u t i n v o l v e m e n t of th e
gen omi c co rt is ol r e c e p t o r in th e n u cleu s [ F a l k e n s t e i n e t a l . , 2 0 . 0 Alth 0 ] ou gh th es e were b as ed
on th e ob s ervat i on s wh en cortis ol was gi ven in p h armacol ogical d os e, th ere re mai n s a
p o s s i b i l i t y t h a t t h e s e g e -g n o e m n o i m c i c a n m d e c n h o a n i s m s o f c o r t i s o ls l o bm e a iy n vol a ved in th e effect cau s ed b y t h e u p p er levels of p h ys iol ogi cal d o s a g e o f c orti s ol s h own in th e cu rren t
s tu d y.
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 93 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
T h e s e p os s ib le con tri b u ti n g factors remai n to b e e l u c i d a t e d i n t h e f u t u r e i n , v b e u s t t i g a t i o n
th is s eri es o f e x p e r i m e n t s c o n c l u d e d t h a t u p p e r p h ys iol ogi cal le vel o f c ortis ol can s u p p r e s s p e r -
N K -c e l l c y t o t o x i c a c n t d i N v i k p t 4 y 6 e x p r e . s s i o n
4 . 2 . 1 . E 3 n d o g e n o u s l e v e l s o f s t -S) r e an s d N s K C A h o r m o n e s ( c o r t
T h e o t h e r p r o p o s e d s t r -as e s s oci at ed h or mon es , i .e . D H E A -S a n d m e l a t , o are n i k n own to b e an tagon i s t i c agai n s t t h e s u p p res s ive ef fects o f co rtis ol u p on l ymp h oc ytes as d es crib ed in th e
i n t r o d u c t i o n [ 1 . 2 . 2 . 3 a n d 1 .2 . 4 . 2 ] , b u t ht e res u lt s d e m o n s t r a t ed th at th ere was n o s i g n ifican t
r e l a t i o n s h i p b e t w e e n e n d o g e n o u s l e v e l s o f -a s s t o r c e i s a s t e d h o r m o n e an s d th e NKC A le vel s
b e f o r e t h e i n c u b a t i o n o f P B M C s . H o w e , v th e r ere ap p eared to b e p o s i t i v e r r e c l o a t i o n bs etween
e n d o g e n o u s l e v e l s o f s t -a r e s s s o c i a t e d h -S o an r d mel m o at n on e in s ) an d ( th D e NH KC E A
l e v e l s a f t e r 2 4 h r s i f n r c e u e b a t f i r d o o m n g e n e o n u s h o r m o n e s.
This fin d in g was h yp ot h es is ed to b e a s s o c i a t e d w i t h t h -S e l o n g t
a n d m e l a t o -cells n i n b al an u ce p o wi n th a sN u pK p res s ive effect of c ortis ol . In ot h er word s ,
t h e d i f f e r e n c e b e t w e e n t h e s e N K C A l e v e l s m iated a y wi b e th a ts hs e o sc tage of al ar m to
r e s i s t a n c e a n d th e s tage of exh au s tion in S e l y e’s clas s ificati on [1 . 2 . 4 ]: . 1
N K -cel l s wi t h h i gh N KC A le vel a fter 2 4 h ou rs in cu b ation (with h igh levels of
D H E A -S an d mel at on in ) ma y b e mixtu re of N K -cells in a s ta ge of a l a re a r c t m i o n
an d res is tan ce w h e r e c e l l s a r e a b l e with t o b ot r e h s act p o in vat d ion an d in h ib ition
fro m th e vari ou s fact o rs i n cl u d in g h ormo n es , s o th e y can b e acti vated wh en va riou s
inhibi t o r y f a c t o r s ( i n c l u d i n g e n d o g e n o u s c o r t i s o l ) w e r e r e m o v e d ; a n d
N K -c e l l s w low i t Nh KC A le vel a ft er 2 4 h ou rs in cu b ation (with low le vels o f
D H E A -S an d mel at on i n ) ma y b e N K -cell s in an exh au s ted s tage, s o th e y can n ot
res p on d .
Th is h yp ot h es is can b e s u mmaris ed an d p arap h ras ed b y s t a t i h a n t g th e s u p p res s ive effects o f c o r t i s o l u p o n K-c e N l l s i s c o u n t e r : a c t e d b y
D H E A -S: a n o t h e r m a j o r a d r e n o a x c i s; o r a n t d i c a l h o r m o n e
Me l a t o n : i a n m a j o r h o r m o n e as s oci at ed wi th s leep in th e c i r c a d i a n rh y t . h m
In o r d e r t o t e s t t h i s h yp o t h e s i s , t h e d i u r n a l p a t t e r n i n t h e l e v e l s o f t h e s e h o r m o n e s ogeth t er
with cort i s ol an d d i u rn al ch an ges in th e levels o f N KC A b oth at Tim e 0 an d 2 4 h ours after in
vitro in cub at ion w o u l d n e e d t o b e e x a m , an i n d e t d h e n t h e a s s o c i a t i o n th ese
b e t w e e n
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 94 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
comb in at ion s w o u l d n e e to d b e an al ys ed in fu tu re in vitr o s t u d i e s i n v e s tigatin g th e effect of
s t r e s s-a s s o c i a t e d h -cell o r s . m o n e s u p o n N K
N o n e t h e l e s s , t h e r e s u l t s s u p p o r t t - h e d i r e c
c e l l s a s a p a r t o f -n e t u r h e o-e n p d s o y c r h i o -i n o mmu n e n et wo rk.
4 . 2 . Ch 2 a n g e s -cells i n a f t T e in r vitro i n c u b a t i o n
O n e o f m a j o r f u n s c t o i f o -c n e l l T s in s e l f-d e f e n c e i s t h e a p b r i o l i f i e r t a te y an t d o ge n erat e
a p p r o p r i a t e c e l l p h e n o t y p e s w h i c h h a v e s a p e f c f i f i n i c a g t a y i n s t a s p e c i f i c a n t i g e n . O n e m e t h o d
u s e d t o m e a s u r e t h i s a b i l th i e t [ y h a s b e e n
3 H ] -t h ym i d i n e i n c o r p o r a , t roli i p o n ferat i v e T-c e l l
res p on s e as s a y [ W e y t s e t a l . , 1 9 9 b7 as ] ed on th e fi n d in gs th at in vitr o stimulation with a
m i t o g e n , s u p e -a r n t i g e n o r s p e c i f i c -c e a l n l t s i r g e s u n l s t i a n g c t i i n v [ p a An r t o tia l e i et s f e r T a t i o n
a l . , 2 0 0 3 ; K a e c h & A h m e d , 2 0 0 3 ; S e d e r & A h m e d , . 2 0 0 3 ]
It i s w e l l-kn own t h at p h armac olo gical le v els of c ortis ol ( or glu coc ortic oid s ) can s u p p res s
th e p rol iferat i ve res p on s es of h u man cells [ H e t t m a n n s p e r g e r e t a l . , 1 9 9 . 3 In ] th e cu rren t s tu d y,
t h e p pu er ph ys iol ogi c al lev el o f c ortis ol ( 2 5 0n M) was als o s h own t o s u p p r e s s T-cells’
p roliferat i ve res p on s es a g a i n s t m ito gen , s u p er an tigen an d recall a n t i g e n s, a n d e x p r e s of s i o n
t h e i r c e l l-s u r f a c e m a r k e r s w e r e con m e cu a s rren u r e tl d y in o rd er t o in ves tigat e th e p os s ib le s ites
of th e s u p p res s i ve effe ct s of co rtis ol.
4 . 2 . 2 . E 1 x p r e s s i o n o f C D 2 5 d u r i n g p r o l i f e r a t iv e r e s p o n s es
Th e p rol ifer at ive res p on s e i n -l ymp T h oc yt es con s is ts of f ou r p r oces s es : (1 ) r eco gn ition of
a s timu l u s ; (2 ) act i vat i n g cel l c ycle p r ogr es s ion ; (3 ) p roces s of actu al c ell d ivi s ion ; an d (4 )
ap op tos i s of e xces s i ve cel l s . W i t h i n t h i s p r o c e s s , t h e f o l lowin g tw o p os s ib ilities for s u p p res s ive
e f f e c t o f c o r t i s o l o n t h e p r o l i f e r a t i v e r e s p o n s e s w e r e : i n v e s t i g a t e d i n t h e
1 . D e c r e a s i n g a c t i v a t i o n , a n d
2 . In cre as i n g ap op t os i s .
Fl o w c y t o m e t r y t e c h n i q u e h a s b e e n i n t r o d u c e d t o i s e m x s a of m i n e t h e m e c h a n
p r o l i f e r a t i v e r e s p o n u s s e s i n g s o m e maj o r cel l s u rface acti vation mar kers , i.e. C D 6 9 , C D 7 an 1 d
H L A -D R , b u t i t w a s s h o w n t h a t o t f h t e h e s e x p m r a e r k s e s r can i o n ot b e al t ern at ives to P h . D . a t U n i v e r s i t y o f L o n d o n - 1 95 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
reflect th e le vel s of p r ol ifer ation in c o m p a r i s o n w i t h e h m e t h o d u s in g th e [ 3 H ] -t h ymid in e
i n c o r p o r a t [ i C o a r n u s o e t a l . , 1 9 9 7 ; H u t c h i n s o n e t a l . , 1 9 9 9 ; R u t e l l a e t a . l . , 1 9 9 9 ]
I n t e r l e u -2 k i ( n I L 2 ) i s k a n s o w a n m a j o r c y t o k t i o n e i n -cell d u c p rol e if erat T ion b y b in d in g
w i t h t -2 h e r e c I e p L t o r , i . e . C D 2 5 , -C D2 a n d 5 in t teract h i s ion I L is 2 al s o kn own to b e es s en tial
f o r -cells T t o p r o l i f e r a t e w i t h o t h e r stimuli c y t o k i [ M n e a l e k e t a l . , 2 0 0 . 1 He ] n c e , o n e o f th e
a b o v e h y p o t h es es o f s u p p r e s s i v e e f f e c t s o f c o r t i s o l u p o n p r o l i f e r a t i v , e th r at e s cort p o n i s se ol s
d e c r e a s e s a ati c t on i pv roces s o f -l y T m p h o c y t e s, w a s t e s y t e x d a m b i n i n g t h e l e v e l s o Cf D2 5
e x p r e s s i o n t h e c e l l s u . r f a c e
T h e e x p r e s s i o n o f C D 2 5 i n t h e c u r r e n t s t u d y s h o w e d a d r a m a t i c i n c r e a s e 4 8 a f ht ou e r rs of
i n c u b a t i o n w P HA i t h o r P P D , b u t this i n c r e a s ed r a t e w a s a g a i n n o t d ec reas ed b y th e
p h ys iol o gi cal level of co rt is ol. He n c e , a l t h o u g h th e p o s s i b i l i t y o f i m p a i r m e n t i n o t h e r a c t i v a t i o n
m a r k e r s o n t h e c e l l s , u r f a c s e u c h -DR , a is s ti ll tH o L b e A e x a m i ne d i n f u ture e x p e r i m e n t , s it
a p p e a r s that th ere ma y b e an oth er u n id en tified m e c h a t h n a t i h as s a m g r e a t e r i m p a c t on th e
s u pp res s i ve effect o f c ort i s ol in p r olifer at ive res p on s es .
4 . 2 . 2 . Exp 2 res s ion o f C D 9 5 an d An n exin V d u r i n g p r o l i f e r a t iv e r e s p o n s e
P r e v i o u s l y i n t h e l i t e r a t u r e , t h a i t a l w t a e s r i r n g e p t o r h e t e ol d rtis e v e ol l in o f ca rp c
l ymp h oc yt es wa s as s oci at ed w i t h in a n cre as e in ap op tos is d u ri n g th e p roliferati on r es p on s e to a
mito gen (P HA) an d a s u p e r -a n t i g e n s u c h a s l i p o p o l y s a c c h a r i d e ( L P [W S ) e y t s e t a l . , 1 9 9 . 7 In ]
t h e i r s t u d y , t h e r a t e o f a p w o p a t s o s m i s e a s u r e d t b h y e m e t h o d u s i n g T t d -med h T e i at ed d UTP
n i c k e n d l a b e l l i n g ( T U N E L as ) s a y, s o th e act u al ap op tot ic p r oces s in a n u cleu s was d etected an d
t h e a m o u n t o f a p o p t h o a t n i g c e s c w a s m e a s . u r e d
Ap op tos is i s k n o w n t s o t a e r i t h t e r th e c f e l l -s r u o r f m a c e m e c h (e.g a n . a i c as s cad m e
in d u ced b y C D 9 5 / F a s an d C D 9 5 L/ F a s-l i g a n c d o n t a c t s) o r th e c yt op las mi c m ech an is m (e. g.
m i t o c h o n d r i a re l e a se s th e c y t o c h r ; o a m e g e n o C m i c c a s c [ a B d e d n e r e t a l . , 1 9 9 9 med ] iat ed b y
B a x c o m p l e x e s w i t h i n n a u c l e u s). F o r t h e p u r p o s e o f d ap e op t e tot c t ic i ch n g an ge on th e cel l
s u rface, a met h od u s in g An n exin V wh ich can b i n d t h e p h o s p h a t i d y l s e r hi as n e b een d e v e l o p ed
[ v a n E n g e l a n d e t a l . , 1 9 9 . 8 P ] h o s p h a t i d y l s e r i n e i s o n e c o m p o n e n t t o h f e c e l l-m e m b r an e an d it is
l o c a t ed i n s i d e t h e memb ran e in live cells ; an d it comes ou t s id e of th e memb ran e w h en th e cell
d i e s a n d l o o s e s t h i s t i g h t c o n t r o l.
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 96 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
I n t h e c u r r e n t s t u d y , s h a r p i n c r e a s e s i n t h e l e v e l s on o f th e t h e C D 9 5 ( F a s ) e
s u r f a c e o f C D 4 a n d 8 T-c C D e l l s were ob s erved aft e r 2 4 a n d 4 8 h ou rs i n v i in t cub r o at ion wi th P H A o r P P D , b u t t h e p h y s i o l o g i c a l l e v e cl ortis o f ol d id n ot in fl u en ce t h e s e in creas es . Fu rth er ,
t h e p h y s i o l o g i c a l l e v e l o f c o r t i s o l d i d n o t a f f e c t t h e l e v e l s o f A n n e x i n V o n t h ace e c afte e l l r s u r f
4 8 h o u r s i n c u b . a Hen t i o ce, n it was c on cl u d ed th at cortis ol d id n ot alter ap op totic c ell s u rface
c h a n g e s o n p r o -l l ymp i f h oe c yt r es a . t In i ord n g er t o T c on fir m th e ap op totic ch an ge b y th e
p h ys iol o gi cal level of c o r t i s o l f u r t h e r , t h e T U N E L a s s a y n e e t d s o b ed e . p e r f o r m
O n t h e o t h e r h a n d , i n t h e ortis n u c l ol e u h s a s , b c e e n s h own to inhibit th e N F - B acti vation
[ B a r n e s , 1 9 9 7 ] an d to in du ce a n e a r l y G1 p h a s e b l o c k i n c e l l-c y c l e ( G 1-S-G 2 -M ) p r o g r e s s in i o n
a tu mou r cel l li n e [ S a n c h ez e t a l . , 1 9 9 3 res ] u lti n g in d el a y of th e c e l l d i v . i T s h i e o p n r o c e s of
a c t u a l c e l l d can i v i b e s m i e o a n s u r ed b y th e met h od u s in g carb o x yf lu ores cein s u cci n imid yl es ter
( C F S E ) [ L y o n s , 2 0 0 0 ], i n w h i c h l e t v h e e l o f in ten s it y of th e C FS E can b e meas u re d in th e
s t a i n e d c e l o l f s t h c e y t o an p d l this a ls ev el m h al ves wi th each cell d ivis i on . Hen ce, fu tu re
i n v e st i g a t i o n o n e f t f e h c e t o f c o r t i s o l u p o n T-l y m p h o c y t e s s h o u l in d clu d e t h i s c e l l-c ycl e
p r o g r e s s i o n a n a l y s i s i n a d d i t i o n t o t h e f u r t h e r a n a l y s e s o f a p o p . t o t i c c h a n g e s
N e v e r t h e l e s s , th e p h ys i ol ogi cal level of c ortis ol was s h own to s u p p res s h u man T-c ell s
p r o l i f e r a t i v e r e s p o s. n T s h e i s m a y o r m a y n o t i n c r e a s e a p o p t o s i s , b u t i t n h c i r s e a p o s e s d i b l e
ap op tot i c ch an ge b y c ort i s ol was n ot d etected th rou gh th e ch an ge on th e cell s u rf ac e.
Th e s e i n v i e x t p r e o r i m e n ts d emon s trat e t h e feas ib ilit y of th e en d o c r i n -i o m m u n e etwor n k.
Th e in v i t m r o d e l o f s t r e s s w a s s h o w n t o s u : p p r e s s
N K -cell f u n c t i , o i n . e . p -N e r K -c e l l y t c o t o x i c a c t i v i t y t o t u m o ; r a c n e d l l s
T-c e l l f u n c t , i .e. o n p r ol ifer at ive res p on s e to s u b s tan ces related to in fecti on .
In ad d it ion , D H E A -S ( i n a oco d r e rtical n h o rm on es ) an d melat on in (in h orm on es
as s ociat ed wi th ci rcad ian regu lati on ) ma y h ave a n t a g o n i s t i c a s s o c i a t i ao gain n s s t co rt is ol as
s h o w n b thei y r e f f e c t s N -c K o e l n l f u n c t . i o n
T h e s e supp ort that t h e r e i s a d i e e r n e h o c r m t o n e s r ( e c o l r t a i s t o l rt i , icu o i lar, n s p a h i p b e t
a n d D -S H E A a n d m e l a t o n i n ) -c e a l n l d s -l ymp i a n m d hm oc u yt T n es e ) an d c d emon e l sl trate s ( N K
p os s ib le in teract ion wi th in the p s y c h -n o e u r o-e n d o c r i n -i o mmu n e n et wo rk.
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 97 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
4.3 C o n c l u s i o n s
Th e i n v i s v t o u d y u s i n g u n i v e r s i t y s t u d e c n o t n s f i r m e d t h a t e x a pm arati p r on e s p rov o ke
a n x i e t y a n d i n c r e s a t s r e s s in s t u d e n t . s T h e s t u d y s h o w e d t h a t s t r e s s p e r c e p t wi as o n as s oci at ed
with N K c y t o t o x i c a c t i v i t y ; l e a v n e d l i s t d e m o n s trat ed th at p s ych ol o gical in ter ven tion ma y
b u f f er a n d / o r r e v e dr etrimen s e tal e f f e c t s o f s t r e s s u p o n t h e i m m c u e n lls, e p art icu larl y th e e ffect s
o n -cells N K . Th e i n v i sv tu o d y u s i n g -in fect H ed I iV n d ivi d u al s con fi rmed th at th ere is a s tead y
d e c l i n e i n -cell C D c4 ou nT ts in th e p a t i e n t s w h o a r e n o t r e c e i v i n g a n t i-r e t r o v i r a l t r e a t m e n t; an d
it d e m o n s t r a t d e th at p s ych ol o gi cal in ter v en tion m a y d e c r e a s thi e s d e c l i . T n e h e s e e ffect s we re
p articu l arl y as s oci at ed wi t h th e t r a i n i n g a n d p r a c t i c e o f J o h r e i.
In ad d it ion , the d ecl in e i n C D -c 4 e T l l c o -in u n fect t ed s p at ien i ts n w a s H I f o V u n d e t o b
p o s i t i v e l y a s s with o c i a d t e c e l d i n s e in th e p ercei ved q u a l i -o t f y -l i f e c s o r es. Al th ou g h a large r
s a m p l e o u l s d i b e z n e e d e d w f o r s t a t i s t i c a l , s Ji oh g n rei i f ap i c pa eared n c e to i mp ro ve th es e
q u a l i -o t f y -li fe s co res . T h e se r a i s a e p o s s i b i l t i h a t y i m p r o v e m e n t o f t -f h o e c u s m e d a o n c p i n g
skills m a y h a v e b e n e f i c i a l e f f e c t s u p o n d i s e a s e p r o g r e s s i - o an n d m /or o r e t h a n t h e e m o t i
p r o b -f o l c us e d m c o p i n g s t r a t e g . i e s
In vitr o e x p o s u r e t o t s th res e s h orm on e, c o r t i s o l , s u p p res s ed N K -c e l l a n d -l y m T p h o c y t e
fu n ction s . Ot h e r s t r e -a s s s s o c i a t e r d m h o o n es ( D H -S E an A d m el at on in ) ap p eared to b e
an tagon is ti c a g a i n s t t h e e f f e c t n o f c N -c o K r e t l i l s o f l u n c . o t i T e o s h n e s h owed d irec t in teract ion s
o f s t r e s s h o r m o n e s , an d o d emon n sc trat e a l mech l s an is m o wh f ereb y t h e i m m u n e
s t r e s s c o u l d a c t h e s u p y p o c n h o-n e u r o-e n d o c r i o-im n mu n e n et wor k t o r e g u l a t e i m m u n e f u n . c t i o n
T h e s e f i n d i n g s u pp ort th e h yp ot h es is th a t p s ych ol ogi cal in terv en tion m a y c ou n teract th e
d etrimen tal effe ct s of s tres s u p o n p s yc h o l o g i c a l w e l l-b e i n g a n d g e n e r a l actin h e a g l tt h rou h gh a n
inte g r a t e d p s y -n c e h u o r o-e n d o c r i n -i o m m u n e n e t w ; o r a n k d c l e a r l y w a r r a n t t h e n e e or d fu f rth er
i n v e s t i g a t i o n o i f n t e r a c t i o th n s e n e i t n w o r , k p a r t i c u th l e a in r fl l uy en ce of J oh rei u p o n th e
n e t w o r .
k
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 98 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
4.4 F u t u r e d i r e c t i o n s
In ord er t o i n v e s t i g a t e t h e -n e p u s r y o-en c h o d o c r i n -im o mu n e n et work in teract ion s fu rth er,
s everal s u g ges ti on s were rai s ed in th e p r e c e d i n g r e p o r t. Th is s ection lists thos e s u g g e s t i o n an s d
p r o p o se s fu t u re wo rk .
4 . 4 . P 1 s y c h o l o g i c a l i n t e r v e n t i o n s
I n t e r v e n t -f i ree o n c on trol s as wel l as r el ax ation c o n t r ol g r o u p f o r s t u d e n t s s t u d y
A la rg er s a mp le s ize (e. g. m ore th an 8 4 s u b jects p er g r o u p -p f a t o i e r n t s s t H u I d y ) V
4 . 4. 2 Me a s u r em e n t s
4 . 4 . 2 . P 1 s y c h o l o g i c a l m e a s u r e s
C o m p a r i s o n a n a l y s i s b e t w e e n t w o s u b g r b o a u s p e s d o : n
1 . T h e m i d l i n e s p l i t o f t h e e s p t i r o e n s s s c p a e l r e f c s o r t h e s t r -r e s e s l a t e d d i f f e r e n c e s :
Th e P ercei ved S t res s S cal e (P SS) [ C o h e n e t a l . , 1 9 8 3 ]
T h e K e s s e l e r P e r c e i v e d S o c i a l S u p p o r t ( K P S [ S C ) o v e n t r y e t a l . , 2 0 0 4 ]
2 . Th e c r i t e r i w o h n e t h e r t h e -o q u f -life a l i sc t y o r e s i m p r o v i n g o r w fo or r s th e n i n g
c h a n g e i n d i s e a s e p r o g r e s s i o n o r m a i n t e n a n c e o f h e a l t h :
Th e S e n s e o f C o h e r e n c e (S o C) [ A n t o n o v s k y , 1 9 8 7 ]
Th e S p i r i t u a l I n v o l v e m e n t a n d B e l i e f s S c a l e ( S I [ B H S a ) t c h e t a l . , 1 9 9 8 ]
Th e P i t t s b u r g h S l e e p Q u a l (P i SQI) t y I [ B n u d y e s x s e e t a l . , 1 9 8 9 ]
3 . A co v a r i a t e f a c t o r : p e r s o n a l i t y t r a i t
Th e T e m p e r a m e n t a n d C h a r a c t e r (TC I n v I) e n [ C t l o r n y i n g e r e t a l . , 1 9 9 3 ]
4 .4 .2 . 2 I m m u n o l o g i c a l m e a s u r e i s n v i v o
N K -cel ls : Pe r -N K -c e l l c y t o t -ce o x l l i s u c b s e t a c c o u t n t s i a v n d i p t e r c y e n , t for a g e s N K
i n d i v i d u a l s w i t h a c u t e o r s u s t a i n e d , b u t l i m i t e d , s t r e s s
P h . D . a t U n i v e r s i t y o f L o n d o n - 1 99 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
C D 4 -c T ells : Su b s e t (Re g u l a t -c o e r l l y i n p T a r t i c u l a r c) ou n ts an d p ercen tages , fu n ction al
m e a s u r e s e . g . T h . 1 a n d T h . 2 c y t o k i n e p r o d for u c t bi ot o h n s h eal th y
indivi d u a l s a n d p a t i e n t s w i t h s u s t a i n e d s t r e s s
4 .4 .2 . 3 In v i t r i o n v e s t i g a t o i n o n -cells N K
C D1 1 b p os it ive mac rop h ages a n a l y s i s c o n c u r r e n t l y w i t h p -N e r K -cel l c yt ot o xi c
a c t i v i t y
N F -k B a n a l y s i s w i t h c o r t i s o l r e c e p t o r ( G C R ) a n a l y s i s
Di u r al n p attern in th e e n d o g e n o us s t r e s s h o r m o n e l e v e l c s o n c u r r e n t l y th w e i Nt KC h A
levels b ot h at Ti me 0 an d 2 4 h ou rs after i n v i t i r n o c u b a t i o n
4 . 4 . 2 . I 4 n v i t r i o n v e s t i g -l a t y m i p h o n c y t e o s n T
Cell-c y c l e p r o g r e s s i o n a n a l y s ( e i . s g . C F S E a n a l y s i s )
T U N E L a s s a y f o r p r o l -l i y f m e p h r o c a y t s e i v e T
4 .4 .3 P r o p o s a l f o r f u t in u r vivo e s t u d y
Eth ical ap p roval an d fu n d i n g h ave b een g ran ted for a fu rth er s tu d y in to th e e ffects of
J o h r e i i n H I V p a t i . e T n h t e s p r o p o s a l a i m s t o i n v e s t i g a t e t h e -n e i u r n t o-e e n g d r o c a r t ino- e d p s y c h o
i m m u n e n e t w o r k i n t e r a c t i o n s ; an d to con f irm an d exp lo re th e majo r r e s u l t s fr om th e P h .D.
p roject th at J oh rei ma y h ave b en eficial ef fect u p on d i s e a s e p r o g r e , s (m s e i a o s n u r e d C i D n 4 -T
c e l l c o u n t s), i n -i H n f I e c V t e d i n d i v i d u a l s n o t r e c e i v i n g a n t i-r e t r o v i r a l t r e a t m e n t [ A p p e n d i x 7 ].
R e f e r en c e s
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J . , K l i m a s , N . , F l e t c h e r , M . A . , & S c h n e i d e r m a n , -be N ha . vio ( r2 a0 l 0 s0 t re ) . ss C o g n i t i v e
m a n a g e m e n t r e d u c e s d i s t r -h e s s o u a r n d 2 4 u r i n a r y f r e e c o r t -i
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P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
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P h . D . a t U n i v e r s i t y o f L o n d o n - 2 12 - I m p e r i a l o C n o d l o n l e g e L

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1 7 8
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 13 - I m p e r i a l o C n o d l o n l e g e L

A p p e n d i x : 1 Ethi c s a p p r o v a l , i n f o r m a t i o n s h e e t a n d c o n s e n t
R I V E R S I D E R E S E A R C H E T H I C S C O M M I T T E E
A P P L I C A T I O N F O R M
I f y o u r e q u i r e m o r e s p a c e t o a n s we r a
q u e s t i o n t h e n p l e as e a d j us t t h e s i z i n g
o f t h e a n s we r s p ac e ac c o r d i n g l y .
- 2 14 -
V e r s i o n 2 0 0 3 . 0 1
N a m e o f L e a d I n v e s t i g a t o r: P r o f . J o h n H G r u z e l i e r
D e p a r t m e nt : C o g n i t i v e N e u r o s c i e n c e a n d B e h a v i o u r
A d d r e s s : Ch a rin g C ross C ampu s, Imp eri a l C olleg e Lon d on , St Dun stan 's R oa d,
L o n d o n , W 6 8 R F
[1] Please state project title.
T h e E f f e c t s o f T w o P s y c h o l o g i c a l I n t e r v e n t i o n T e c h n i q u e s , -Hy S e l pn f os is a n d th e
J o h r e i H e a l i n g M e t h o d, o n Q u a l i t y o f L i f e , P s y c h o l o g i c a l W e l -B l eing , E E G
m e a s u r e s a n d V a r i o u s I m m u n o l o g i c a l M e a s u r e s i n c l u d i ounts n g C iD n 4 ea + rl c y
HI V: A Ra nd o ml y Con tr oll e d P ilo t Stu dy .
[2] What question is the project seeking to answer, and what will be the value of
obtaining this answer? This should also be clearly explained within the
p a t i e n t i n f o r m a t i o n s h e e t .
Whe n pat ie nts ar e ne wl y dia gno s e d wit h HI V, t her e is oft e n a s ub st a nt ia l pe r io d of t ime wh e n
t he ir CD4+ c ount s a r e pre s er ve d , a nd a nt ir et ro vir a l t r e at me nt ( ART) is not r e qu ir e d . Pa t ie nt s ar e
h e a l t h y i n a l l o t h e r r e s p e c t s , a n d j o b s a n d h o m e l i f e c a r r i e s ounts o n . f all O v ae nr d t i m e , C D 4 + c
ult ima t e ly mo s t pa t ie nt s s ta rt to ta ke ART . Ou r pr ima r y q u e st io n is wh e t he r we c an p ro lo ng t h is
s t at e .
T h i s p r oj ec t s e e ks t o i n ve s t i ga t e t he p os s i b l e i m p a c t u p o n Qu a l i t y o f Li f e , p s yc h o l o gi c a l we -l
l
b e i n g , v a r i o u s i m m u n e p a r a m e t e r s l t h a n s d t a t h u e s a o f t w o i n t e r v e n t i o n s , -hypnos s e l f is a nd J ohre i
( a J a p a n e s e h e a l i n g m e t h o d ) . A t h i r d g r o u p w i l l b e p u t o n a w a i t i n g l i s t a wa n d i t a -l c t i a s t ' ‘ e d
c ontr ols f or t he f irs t 4 mont hs of t he s tu dy. Su bj e c ts wil l be r a nd omly a s s ign e d a ft er
s t r a t i f i ca t i on on CD4+ le ve ls t o on e of t hes e th r e e gr ou ps .
T h e p u r p o s e s o f J o h r e i a n d s e -hypnos l f is a re s imila r . Ea c h t e ch niq ue will be t a ugh t to par t ic ip a nts r a ndomly a s s igne d t o t he s pec if ic in t er ve nt ion wit h t he pur pos e s of a id in g in ps yc ho lo gic a l
a dj us t men t t o t he ir c ondit ion, ma int a in in g t heir qu a lit y of lif e an d bo lst er in g t he ir immu no lo gic a l
de f enc e s ys t e m t hr ough da ily pr a ct ic e . I n ad dit io n , c ogn it ive a s se s s me nts wil l be un der take n
us ing e le c t ro phys iologic a l ( EEG) me a su re s .
S h o u l d p a r t i c i p a n t s m is a si ta n t e a wh i n e r e t he h ir CD4+ c ount s r e ma in high a nd ph ar ma c olo gic a l
t r ea t m en t i s s t i l l d e e m e d u n ne c es s ar y, o r t h at t h e i r q u a l i t y o f l i f e an d ps yc h o l o gi c a l we -be l l ing is
s i g n i f i c a n t l y b e t t e r t h a n t h o s e w i t h o u t t h e i n t e r v e n t i o n ns s , c ould e i bt e h e r o f t h e s e t w o
e a s ily a dd e d t o t r ea t ment pr ot oco ls in e ar ly HI V.
T he s e t wo in t e r ve nt ions a re in a d d it io n t o b est c o n ve nt io n a l me d ica l c a re give n b y t h e Ch e ls e a &
We s t min s te r He a lt hc ar e NHS Tr u st , a nd wil l b e a d min is te re d wit h t h e p ar t ic ip at io n of c lin ic ia n s
invol ve d in t h e pat ie nt s ’ c ar e .

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
[3] Please provide an outline of the project, this should include procedures to be
used, measur es to be made, justification of sample size & plans for statistical
a n a l ys i s . [Paras2.1-2.8]
T h e t w o i n t e r v e n t i o n s a r e s -hypnos e l f is a nd the J ohr e i he a ling me t ho d f r om J a pa n .
H yp n o s i s i s a we l l-r e c ognis e d me dic a lly a c c ep t e d ps yc ho lo gic a l in t e r ve nt io n . It ha s be e n us e d in
ma ny s t ud ie s wit h me dic a l c ond it io ns a nd our la bo r at or y ha s ca rr ie d out a s er ie s of in te r ve nt io nis t
hypnosis st ud ie s ( Fox e t a l, 1999 , Gr uz e lie r e t a l, 20 01 , La id la w e t a l. , 20 03 ) . It ha s be e n us e d in
s ympt om c ont r ol in va r ious me dic a l c on dit ion s , in c lu din g pa in c ont ro l, a nd in no r ma lis in g t he i m m u n e s y s t e m w h e n u n d e r s t r e s s ( G r u z e l i e r e t a l . , 2 0 0 1 ) . I t ovide h a s d p r a bu ff er in t he fac e of
s t re ss ( Gr uz e lie r e t a l, 2001, La id la w e t a l. , 20 03 ) . I n t he pre s en t s t ud y, hyp no s is wil l be t au gh t a s
a s k i l l s o i t c a n b e p r a c t i s e d i n t h e f o r m -hypnos o f s e l f is in t he pr iva c y of t he pa rt ic ip a nt s ' own
h o m e s . -going O n suppor t a n d s u p e r v i s i o n w i l l b e p r o v i d e d t h r o u g h o u t t h e s t u d y p e r i o -d
. S e l f
hypnos is wil l be t a ught by a n e xpe rt in me dica l hyp no s is .
I n Ja pa n a nd ma ny ot her count r ie s, s ome 3 millio n pe op le pr ac t ise th e Jo hre i lif e s t yle a nd he a lin g
m e t h o d . I t i s p r i m t a r i s l e d y i p r n a c t h e f a m i l y s e t t i n g a n d i n v o l v -s e s t yle a ah ne d a l t h y l i f e
a ppre c ia t io n of be aut y. I n t he f irs t pu blis he d Jo hr e i st ud y, me dic a l s t ud e nt s illu s tr a te d t hat pr a ct is in g J oh re i pr ovide d he lp in c op in g wit h e xa m s tr e ss . An in t r odu ct io n to J oh r e i will be ta ught t o pa rt ic ipa nt s , a nd s uper vis ion f or part ic ip a nt a nd f a mily me mb e r or a not her su pp ort
pe r son will be pr ovide d t hrough ou t t he st ud y pe r io d , a s in t he Hyp no s is c ond it io n . Jo hre i will be t a u g h t b y a m e d i c a l d o c t o r w h o h a s b e e n t r a i n e d i n t is ed J o h it r se in i ce a n ch d ildhood. p r a c
T he f ou r a re a s of outc ome mea s ur e s a re immu no lo gic a l va r ia ble s , ps yc ho lo gic a l va r ia ble s ,
c o g n i t i v e v a r i a b l e s a n d , f o r t h e t e r m o f t h e s t u d y , m a r k e r s o f p r o g r e s s i - o n o f d i s e a s e , a s s e
i n t e r v e n t i o nd n at a t he f i n i s h o f t h e study. A t t h e b e g i n n i n g o f t h e s t u d y ipants , a l l wil p l a r t i c
p r o v i d e d e s c r i p , t whic i v e h wi ll in c lude de mogr a phic det a ils a nd me dic a l hist or ies .
S t u d y d e s i g n
T his r a nd omis e d c ont r olle d t r ia l wil l in c lu de 15 0 pat ie nt s wh o ha ve bee n dia gn ose d wit h HI V but a r e n a ï v e-t o-tr ea t ment , mea nin g t hat t he ir CD4 + co unt s ar e s uf f ic ie nt ly high t ha t ART is not indic a t e d. Re a lis t ica lly, t his me a ns t hat t he CD4 + c ou nt is < 40 0 bu t a bo ve 200 ( irr e sp e ct ive of vir a l
loa d) . T he st ud y dur a t ion f or ea c h pa rt ic ip a nt is a pp ro xima t e ly 5 mo nth s . Th e pla nn e d mon th ly
int a ke is of 6 – 9 pa t ients t o e ac h of th e t hre e gr ou ps ( i. e. 18 - 27 ne w pe op le ea c h mon t h) .
T he thr ee gr ou ps wil l be r e cr uite d th r ou gh Dr Simo n Ba r t on an d his c lin ic a l c olle a gu e s at Ch e ls e a
& W e s t m i n s t e r H e a l t h c a r e N H S t . T r An u s in de pende nt st at is t ic ian wil l r a nd omly a s s ign
pa rt ic ip a nts t o e ithe r one of t he t wo in t er ve nt io n gr ou ps or t he wa i t -l i s t ce ont d r ol gr ou p us ing a
s t ra t if ied ra nd omis at ion on CD4 + c ou nt s.
O u t c o m e m e a s u r e s w i l l i n c l u d e t h e p s y c h o l o g i c a l q u e s , t blood i o n n a an i r d e s ur ine sa mple s f or
immune a s sa ys , a nd c ognit ive da t a de ta ile d be lo w a nd illu s t r a te d in t he dia gr a m f ollo win g.
Ba s ic a lly, t he des ign invol ve s 8 s e ss io ns wit h t hre e maj or a ss es s me nt po int s ove r , at th e mo s t , s ix
mont hs. T he f ir st f our s es s ions in t he f irs t mon t h ar e int er ve nt io n int e ns ive , fo llo we d by 4
m o n t h l y -up sf e s so ion l s . l Ea o cw h tr a ining s e s s io n will t a ke a bo ut 2 ho ur s a nd is plan ne d t o be he ld a ft er wo r king hour s a t t he Ch ar in g Cr os s Ca mp us s it e . P ar t ic ip a nt s will be r e cr uit e d
mont hly to be in training groups of 6 – 9. Th e t hr ee as s es s me nt po in t s inc lu de a ll t he
immuno lo gic a l a nd ps yc hologic a l t es ts des c r ib e d be lo w a nd de s ign a t ed a s out c ome me a su re s .
I N T E R V E N T I O N G R O U P S S C H E D U L E
1 2 3 4 5 6 I 7 n t e r v e n t i o n s s i s o e n s ( f i r s t 4 a r e w e e k l y , l a s t 3 m o n t h l y )
1 &2 3 M a i n a s s e s s m e n t p o i n t s
E nd o f Mo nt h: 1 2 3 4 T i m e
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 15 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
W A I T-L I S T E C D O N T R O L S C H E D U : L E
0 1 2 3 4 5 6 I n t 7 e r v e n t s i e s o s n i o n s
1 &2 3 4 M a i n a s s e s s m e n t p o i n t s
E nd o f Mo nt h: 1 2 3 4 5 6 T i m e 7 8
A s s e s s m e n t v a r i a b l e : s
P s y c h o l o g i c a l v a r i a b l e s : ( S t e h r o i s e s n 1 o t n e r e p d e i t i n t g i o n )
H y p n o t i s a b i l i t y a n d i m a g i n a t i v e a b i l i t Crea i e s : t ive I ma gina t ion Sc a le ( Wils on & Bar ber , 197 8 ) ,
a n d S t a n f o r d H y p n o t -C) i ( We c is en hS off u er s & c Hilga e p r d, t 19 i 62) b . i I t l is i t y S c a l e
h y p o t h e s i s e d t h a t h y p n o t i s a b i l i t y o r a b i l wil i t l y inf t lu o e nv ci e s u the a l outc i s e ome va r ia bles ( L a i d l a w e t a l . , 1 9 9 6 )
P e r s o n a l i : t Ty o st ud y per s ona lit y t ype s a nd co pin g s t yle s in r e la t io n t o pr ogn os is. ( Wat s on e t a l. ,
1 9 8 4 ) . A s s e s s e d w i t h t h e -Cr M a own r l o w e e So c ia l De s ir a bilit y Sc a le ( Cr own e & M ar lo we , 19 60) and the Cou rt old: ( Bar ge r , Kir c he r & Cr oyle , 19 97 ). Tr a it an xie t y fr om Sp ie lb e r ge r 's STAI
( Spie lbe r ge r , Gors uc h & Lus he ne , 197 0) , a nd Pe r so na lit y Syn dr ome Qu e s t io nn a ir e ( Gru z e lie r ,
2000)
Social Support: So c i a l s u p po r t h as b ee n l i n ke d t o m en t a l h e a l t h o f p at ie nts . I t c a n be ea s ily
a s s e s s e d w i t h -min t h e Si gn 1 0 if ic a nt Ot he r s Sc a le (Po we r s , Ca mp io n & Ar is , 198 8 ) . Fur th e r t o
t his is a s c a le t o a ss e ss s pir it ua lit y ( Ha tc h et al. , 19 98 ) .
P s y c h o l o g i c a l v a r i a b : l S e s e r i e s ( d 2 e p e n d e n t v a r i a b l e s )
D e p r es si o n an d a nx ie t y : B ec k D e p r es s i o n I n ve n t or y ( B D I , Be c k, 1 9 9 0) ar gu a b l y t h e m o st we -l
l
us e d instr ume nt to a ss es s de pre s s io n in c lin ic a l s t ud ies , as is th e St at e Tr a it An xie t y I nve nto r y
( ST AI , Sp ie lb e r ge r , Gor suc h & Lus he ne , 19 70 ) fo r a nx ie t y.
P T S - D l i k e s y m p t o : m s I m p t a of c Eve nt Sc a le ( IES, Hor owit z , Wiln e r , & Alva r e z , 19 79 ) us e d
wit h HI V dia gnos is as ev e nt in No rd in , Be r gla nd , Glime liu s & Sj od en , 200 1 . Can id e nt if y
i n t r u s i v e t h o u g h t s ( a s s o c i a t e d w i t h h i g h c o r t i s o l w h i c h c a n -h
a v e n e g a t i v e e f f e c t
r e gula t io n ) . P er ce ive d St r e s s Sc a le (P SS) .
Q u a l i t y o f l i f e a n d a c t i v i : t WHOQO y l e v e l s L ( Wor ld He a lth Or ga nis at io n , 19 96 ) in t er nat ion a lly
u s e d s cr e e n f or q ua l i t y o f l i f e c ha n ge s a nd t h e S F3 6 ( J e n ki n s o n e t a l . , 1 9 9 4) , a we -used l l
ge ne r a lis e d in st rume nt f or qua lit y of lif e .
Copi ng : Th e COP E, a mult idime ns io na l c op in g in ve nt or y ( Car ve r , Sc he ier & We in t ra ub , 19 89) inc lude s in fo r mat ion a bout t ur nin g t o s pir it ual s ou r ce s , de nia l a nd dis e nga ge me nt a mo ng oth e r
sub-s c a l e s , w h i c h a r e o f i n t e r e s t i n t h i s s t u d y . L o c u s o f ol. C o n t r
P s yc hol ogi ca l vari able s: Ser ie s 3 ( c o n t i n u o u s d a t a )
D i a r y d : a t P ea rs ona lis e d Emot iona l I nde x (PEI , La id la w, 19 99 ) . Use d wit h pa t ients ( La idla w,
2001). M oo d pa r a me te r s bot h pos it ive a nd nega t ive : an x i ou s , e ner get ic , t i re d , c onf i de nt , uns ur e ,
e l at e d, d e p r e s s e d , a g r e e a b l e , h o s t i l e , -headed c l e a r and i n e f f e c t i r v e a t e d o n a L i k e r t -s
c a l e a s a 5
min da ily dia r y. Addit iona l que s t io ns in c lu de s le e p qu a lit y, ho me wo r k pr a ct ic e , he a lth st at us , a s
m o d e r a t o r v a r i a b l e s t h a t c o u l d i n f l u e n c e o u t c o m e m e l a fa s u ct r ors e s . : s pa E cx e t e f or r n qualit a a t ive
c omme nts af te r t he pr ompt : 'An yt hin g dif f e r en t hap pen t od a y?' r a t e d by r es e ar c he rs on a -3 to +3
s c a le .
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 16 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
C o g n i t i v e v a r i a b l e s
Ne ur ops yc ho phys iologic a l s t udie s wo uld in c lu de e lec tr oe nc e ph a lo gr a ph ic ( EEG) , a nd e l e c t r o d e r m a l t i vi a t c y ( E D A) . T h e se st u d i es w i l l a d d r e s s t h e f o l l o wi n g i s s u e s :
Lat er ali se d br a in funct ion and it s r el a ti o ns hip wi t h i mmun e st at u s , mo o d , c o pi n g s ty le , a nd
r e s ponse t o i nt er v enti on i n pati e nt s: We h yp ot h es is e a r e lat io n s h ip a mo n g t h es e va r ia b les ba s e d
on ear lie r wo r k wit h HI V inf ec t io n ( Gr uz e lie r e t a l. , 1 9 9 6) wh ic h s h o we d t ha t h e mis p he r ic
a s ymme t r y me a s ur es pre dict e d immu n e c o mpe t e nc e a n d we r e c o rr e lat e d wit h mo o d s ta tu s (a ls o
s e e Da vid s o n a nd Toma r ke n, 19 8 9; Ka n g et al. , 1 9 9 1 ; Whe e le r e t a l. , 1 9 9 3; La n e e t
a l . , 1 9 9 7 ; . P a p o u s e k a n d S c h u l t e r , 2 0 0 1 ; G r u z e l i e r e t a l . , 2 0 0 1 )
I m m u n o l o g i c a l m a r k e : r s
- CD pr of ile inc luding numb er s an d pe r ce nt a ges of CD3, CD4 , CD4 5RA/ RO, CD8 , CD1 6 a nd
CD56 ( Va n der P ompe e t a l. 19 97 ) . & CD4 ab s olu te c oun t , CD4 / CD8 r at io a nd HI V vir a l
loa d a s a ma r ke r of dis e as e pr ogr es s io n .
- N K c e l l a c t i vi t y a s m a r ke r s o f a n t i-in f e ct io n in in na te immu nit y ( Eva ns et a l. 200 0)
- Cor t is ol ( ur ine) as a ma r ke r of ch r on ic st r es s a nd st imu la t or of T h2 ( Dh a bh ar et a l. 20 01 ,
E v a n s e t a l . 2 0 0 0 , S c h e d l o 94) w s k i e t a l . 1 9
- D H E A ( u r i n e ) a s a m a r k e r o f T h 1 / T h 2 b a l a n c e w i t h C o r t i s o l ( E v a n s e t a l . 2 0 0 0 )
- M e la to nin (ur ine) c or re la t in g wit h s le e p qu a lit y a nd migh t be a immu ne s t imu lat in g ( T h1
p r e d o m i n a n t l y ) h o r m o n e ( M a e s t r o n i 2 0 0 1 )
- M A O -A I ( a s a m a r k e r o f c a t e c h o l a ) m , i n -g e I N a s F m e c m r a e , t -2, i o Soluble I n L IL-2 r e c e pt or
( a s a T h 1 d o m i n a n -4, t IL-1 c y 0 t o ( k a i s n e a ) , T h I 2 L d o m i n a n t -6, c y CRP t o k i n e ) ( s e r u m )
( a s a ma r ker of inf la mma t ion) .
SAMP LE S IZE C A LC U LAT ION : T he bet we e n gr ou p co mp a r iso ns will t a ke pla c e us ing
Johrei, hypnosis and contr ol gr ou p da ta fr om gr ou ps s ize s of 50 par t ic ip a nt ea c h . T he wit hin gr oup dat a ca n inc lude those par t ic ip an ts wh o ha ve be en in t he c on tr ol gr ou ps pr io r t o be ing
r a n d o m l y a s s i g n e d t o e i t h e r J o h r e i o r -hypnosis. s e l f This will provide up to 75 part ic ip a nts in
e a c h of t he t wo int e r ve nt ion gr ou ps . Th e se nu mb e rs c ome fr om a po we r a na lys is us in g
ST AT I ST I CAL ANAL YS I S: St at i sti c s wi l l be c alc ula te d usi ng SPSS v 11 .
M u l t i v a r i a t e a n a l y s e s w i l l b e u -g s r e d o u p i n c o m t p h a e r i b s e o t n s w , e e a n d r e p e a t se ure d s m ae nd a
c o r r e l a t i o n a l a n a l y s e s f -gr o r oup t ch ha e nge w i s . t h i n
[4] Please specify the source and type of subjects to be recruited and how this will
be done. Also state the expected numbers to be recruited.
1 5 0 p a t i e n t v o l u n t e e r s w i l l b e nt r inuous e c r u i ba t se is d f r om o n t he a c linic o s wh e r e t he y r ec e ive
t he ir dia gn os is unde r t he s upe r vis io n of in ve st iga t or an d c lin ic ia n Dr Simo n Ba rt on .
Re c r uit me nt wil l be via a Re s e ar c h Nur se or by on e of t he in ve s t iga t ors .
I n c l u s i o n c r i t e r i a i n c l u de :
1. H I V p o s i t i v e
2. Age 18 – 70
3. CD4 + c ou nts > 200.
E x c l u s i o n cr i t er i a i n c l u d e :
1. On ART .
2. Abusing drugs or alcohol.
3 . I n a no t he r t r ia l whic h would c o n f lic t .
[5] What will be the duration of the project and where will it be undertaken?
T he proje ct wil l t a ke pla c e at the Depa rt me nt o f Co gn it ive Ne u r o sc ie n ce & Be h a vio u r , 1 0 th f lo o r
of the La b b lo c k, Char ing Cr os s Ca mp u s o f Imp e r ia l Co lle ge Lo n d o n . I t will c o mme n c e wh e n
Et hic s a p pr o va l is ga ine d, a nd c o nt in u e u nt il 1 5 0 p at ie nt vo lu n t e er s h a ve c o mp let e d t he ir tra in in g.
I t i s e st i m a t e d t ha t t his will t a ke a p p r o x imat e ly 1 8 mo n t h s .
[6] Within this project, what treatment and procedures will be performed on subjects
that are extra to normal patient care? These details should be clearly
s t a t e d i n t h e p a t i e n t i n f o r m a t i o n f o r m .
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 17 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
T h e r e a r e n o s if p ic e c tr ea t men t s tr at e gie s f or HI V po s it ive pat ie nts at t his st a ge of t he ir dise a s e.
Nor ma l c ar e in c lude s t he monit or in g of t he ir CD4 + le ve ls . ART wil l c omme nc e wh e n
a p p r o p r i a t e . I n a d d i t i o n t o t h i s m o n i t o r i n g , p a t i e n t s w i l l b ipat e o ing f f e in r e d a c h a n c e o f p a r t i
t h i s p r o j e c t , w h i c h o f f e r s t r a i n i n g i n o n e o -hypnos f s e l f is , or Johre i a s de sc r ibe d a bo ve .
[7] Please state the potential hazards to subjects, if any. What is the probability of
these occurring? What precautions will be taken to meet them? This
i n f o r m a t i o n s h o u l d b e c l e a r l y s t a t e d i n t h e p a t i e n t i n f o r m a t i o n f o r m .
No pote nt ia l ha z ar ds .
[8] What procedures, if any, may cause discomfort or distress to subjects? What
degree of discomfort or distress may this entail? What is the probability of
s u c h d i s c o m f o r t o r d i s t r e s s oc c u r r i n g? T h i s i n f o r m a t i o n s h o u l d b e c l e a r l y
s t a t e d i n t h e p a t i e n t i n f o r m a t i o n f o r m .
Ane c dot a lly, in it ia l s e s s ions of J oh re i oc ca s ion a lly ha ve be e n a ss oc iat e d wit h min or s ymp t oms o f h e a d a c h e o r c o n g e s t i o n . T h i s w a s n o t o ve b s d e r in e it her of t he pr e vious J ohr e i st ud ies do ne at
I mpe r ia l Co lle ge .
[9] Please state the personal experience of the investigator in the field concerned.
Pr of Gr uze lie r has e xt ens ive r es e ar c h e xpe r ien c e in t he f ie ld of HI V ( Ba ld e we g, Ca t a la n et a l,
1995, Ba lde we g, Ric c io e t a l, 19 95, Gru z e lie r et a l. , 19 96 , Ba ld e we g e t a l, 19 97) . He has publis he d ma ny pape rs about hyp nos is in c lu din g it s us e as a n int er ve nt io n a ge nt ( Gr uze lie r e t a l. ,
2001; Fo x e t a l, 1999) , as has Dr La id la w ( La id la w & Wi lle t t , 20 02 ; La id la w, 19 99 ) . His
r e se a rc h t e a m ha s c onduct e d t wo pr e vio us st ud ie s us in g s imila r de s ign s t o t he pr e se nt st ud y
i n v o l v i n g b o t h J o h r e i a n d s -hypnos e l f is ( on e c omple t ed RR 28 83 , La id la w e t a l, 20 03 a nd on e
ongoing, RR2959.).
[10] Written consent should be standard practice, please enclose copies of the
consent form and information sheet. If non-written consent is proposed then
this must be justified to the Committee. [Paras 3.1-3.3]
If a routine clinical procedure precedes or follows what is proposed to be done
by way of this application, the Information and Consent Forms for those
procedures should be also included with Patient Information and Consent
forms for t h i application. s
n/a
[11a] Have the consultants responsible for the overall care of the patient been
informed and their approval given?
Dr Sim on Ba rt on is th e c on s u lt an t res p ons ib le an d is a cu rren t in ves tigator in th is
a p p l i c a t . i o n
[11b] Have you gone through the appropriate process within the Clinical Directorate
in which you wish to undertake your research?
Yes an d recei ved ap p ro val f ro m th e res ea rch com mittee, No ve mb er, 2 0 0 2 .
[11c] Will the subjects' General Practitioner be informed of the recruitment of the
subject before the study begins? Is the subjects consent to this information
being passed as a condition of participation?
[12] Please state any interest, i.e., of profit, personal or departmental, financial or
otherwise, relating to the study. [Paras 7.1-7.2]
Non e.
[13] Does the study involve the administration or application of a medicinal product
or substance? [Para 5.1-5.3]
Yes N o
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 18 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
[15] Please list all staff involved with this project - all staff m u s t s i g n t h i s
section:
N a m e & T i t l e Signature Q u a l i f i c a t i o n ( s ) I n v o l v e m e n t
P rof J H
G r u z e l i e r
Dr TM
L a i d l a w
D r A N a i t o
Dr P
D w i v e d i
Dr D
H e n d e r s o n
Dr Sim on
B a r t o n
R es earch
As s i s t a n t
D a t e o f s u b m i s s i o n :
1 F e b r u a r y 2 0 0 3
N a m e :
P r o f J H G r u z e l i e r
P h D P r i n c i p l e i n v e s t i g a t o r
P h D Overall s u p ervis i on of d ata
collecti on an d p at i en t i n t eraction
with th e s t u d y.
MD an d P h D
c a n d i d a t e
T r a i n i n g i n s e -h l f y p n o s i s
Train in g i n J oh rei an d
immu n ol o gi cal l ab w or k.
P h D EE G d ata c ollection an d an al ys is .
P h D Su p ervis ion of i mmu n ol ogical lab
w o r k
M D C lin ician res p on s ib le for p atien t
treatmen t .
t o b e a p p o i n t e d
Sign atu re of In v e s t i g a t o r :
Ad d res s : Dep t of C o gn i t i ve
Neu ros ci en ce & Beh a vi ou r, C h arin g
C ros s C amp u s , Imp eri al C ol leg e
Lon d on , S t Du n s t an 's R oad , Lo n d on ,
W 6 8 R F
Dat a i n p u t , recru i t men t, lab
as s is tan ce.
C on tact Tel & Bl eep
N o :
0 2 0 8 8 4 6 7 3 8 6
C l i n i c a l T e a m i n w h i c h In v e s t i g a t o r w o r k s : n/a
O t h e r C l i n i c a l T e a m s / D e p t i n v o l v e d i n r e s e a r c h : C h e l s e a & W e s t m i n s t e r H o s p i t a l
N a m e a n d S i g n a t u r e o f C o n s u l t a n t , G P o r C o m m u n i t y P h y s i c i a n i n o v e r a l l c h a r g e . (
You a re
remin de d th a t by s i g n i n g this for m y ou ta ke res pons i bility f or the c ontents a n d
a c c u r a c y o f t h i s E t h i c s C o m m i t t e e A p p l i c a t i o n . Y o u m u s t b e m e d i c a l l y q u a l i f i e d ) :
D r S i m o n B a r t o n
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 19 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Study T i t l e
P a r t i c i p a n t I n f o r m a t i o n S h e e t
T h e E f f e c t s o f T w o P s y c h o l o g i c a l I n t e r v e n t i o n T e c h n i q u e s , -Hyp S e l f no si s
a n d t h e J o h r e i H u a e l i t a y o l f L i f n e , g P sy c ho M e l o g t i c a h l o W d e l l-B , e i ng o , n Q
E E G m easure s a nd Va ri o us Imm unol og ic al M ea sures i n HIV: A Ra ndoml y
C o n t r o l l e d P i l o t S t u d y ( o r ‘ T h e -h S e y l p f n o s i s a n d J o h r e i S t u d y ’ )
I n v i t a t i o n p a r a g r a p h
Y o u a r e b e i n g i n v i t e d t o t a k e p a r t i n a r e f s o e r a e r c h y o u s t d u e d c y i , . it d e is B e i mp o rt an t for
yo u to u n d ers tan d wh y th e res earch is b ei n g d on e an d wh at it will in vol ve. P leas e t ake ti me to
read th e fol l owi n g in f or mat ion ca refu ll y an d d is cu s s it with frien d s , relatives an d yo u r GP if
yo u wis h . As k u s if th ere is an yth in g th at is n ot clear or if you w ou ld like m or e in fo rmation .
Take ti me t o d eci d e wh et h er o r n ot you w is h to take p art .
C on s u mers for Et h ics in R es earch (C ER E S) p u b lis h a leaflet en titled ‘Med ical R es earch an d
Y o u ’. Th is lea fl et gi ves mo re in fo rmati on ab ou t med ical res ea rch an d loo ks at s om e
q u es tion s you ma y wan t to as k. A cop y m a y b e ob tain ed fr om C ER ES, P O B o x 1 3 6 5 ,
Lon d on N1 6 0 B W.
W h a t i s t h e p u r p o s e o f t h e s t u d y ?
We w ou ld li ke t o in vi te you t o b e a p artic ip an t in a 5-m on th lon g s t u d y t h a t i ns d ed i n to t e
f i n d o u t w h e t h e r t h e a d d i t i o n o f -h s e yp l f n os is or a h eal in g met h od called J oh rei t o t h e regu lar
treatmen t you re cei ve at C h e l s e a a n d We s t m i n s t e r H o s p i t a l will h elp clin icall y or i n you r
q u alit y of li f e.
W h y h a v e I b e e n c h o s e n ?
W e w o u l d l i k e amin t o e th e x ef fi cac y o f p s ych ol ogi cal in terv en tion s on th e q u ality o f life in
HIV p at ien ts , s o you h ave b een i n v i t e d t o p a r t i c i p a t e i n t h e p r o j e c t. It is u p to you t o d ecid e
w h e t h e r o r n o t t o t a k e p a r t . I f y o u d o d e c i d e t o t a k fo e rmati p a r on t y o u w i l l b e g i
s h eet to keep an d b e as ked t o s ign a con s en t for m. If you d ecid e to take p art you ar e s till free
to with d raw at an y ti me an d with ou t givi n g a reas on . R efu s al to p articip ate o r s u b seq u en t
w i t h d r a w a l w i l l n o t a f f e c t t h e s t a n d a r d o f . c a r e y o u r e c e i v e
W h a t w i l l h a p p e n t o m e i f I t a k e p a r t ?
Th is res earch p roj ect i s d es ign ed as a ran d omis ed trial.
D r T M L a i d l a w
Depar t ment of Co gni t i v e
Neur os ci en ce & Beha vi our
Charing Cross Hospital
S t D u n s t a n ’ s R o a d
L O N D O N W 6 8 R P
Someti mes b ecau s e we d o n ot kn ow wh ic h wa y o f tr eatin g p atien ts is b es t, we n eed to make
comp ari s on s . I n a r a n d o m i s e d e o t p r l i e a w l i , l l p b e p u t i n t o g an r o d u th p s en comp ared . Th e
grou p s are s el e ct ed b y a c omp u ter t h a t h a s n o in for mation ab ou t th e in d ivid u al – i.e. b y
ch an ce. P at ien ts in each grou p th en h ave a d ifferen t tre atmen t an d th es e are c omp a red .
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 20 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
I n t h i s r e s e a r c h p r o j e c t , y o u w i l l b t o e o r n e a n o d f o t m h l r e y e g a r s o u s p i s : g n s -h e d l yp f n os is o r J o h r e i w h i c h -tou i s ch a h eal n o in n g m et h od fro m J ap an an d a waitin g lis t b efo r e you a re
a s s i g n e d t o e i t h e r s e -h l f yp n os is or J oh rei . P leas e read th e d es crip tion s fo r all th re e gr ou p s .
O n e -t h i r d o f t h e p th e o e p sl tu e d y i wi n ll b e p u t on to th e waitin g lis t to h a ve th eir t rain in g in 4
mon th s ti me, d u ri n g wh ich , if you are in t h is grou p , you will b e as ked t o c omp lete s ome
p s ych ol ogi cal tes ts . Th is d ela y fo r s o me p articip an ts p rovid es a co mp aris on f or th e effects of
train in g ov er th e 4 m on th s , a n eces s ar y re q u iremen t in a s cien tific s tu d y of th is t yp e. Th e
r e m a i n d e r ( 2 / 3 r d s o f p e o p l e i n t h e s t u d y ) w i l l h a v e -o t r h -les e i s r im t mr a ed i in at i el n g y. m o r e
Y o u m u s t f e e l a l l r i g h t a b o u t p a r t i c i p a t i n g r di ela n yed e i con t h e dr it ion t , h as e i m m e d i a t e o
yo u c ou ld b e ran d oml y as s i gn ed to eith er.
Meetin g s ch ed u le :
Ses s i o n s 1 t o 4 a r e h e ( 2 l d h o u w r e s e k a l c h y ). S e s s i o n s 5 t o 1 4 a r e h e l d (1 o n c e a m o n t h
h o u r e a c h ).
I N T E R V E N T I O N G R O U P ’ S S C H E D U L E
1 2 3 4 5 6 7 I n t e r v e n t i o n s e s s i o n s ( f i r s t 4 a r e w e e k l y , l a s t 3 m o n t h l y )
1 & 2 3 M a i n a s s e s s m e n t p o i n t s
End of Month: 1 2 3 4 T i m e
W A I T-L I S T E C D O N T R O L S C H E D U : L E
0 1 I n t e r 2 v e n t i o n 3 s e s s i o 4 n s 5
1 & 2 3 4 M a i n a s s e s s m e n t p o i n t s
End of M on t h : 1 2 3 4 5 6 7 8 T i m e
If you are in th e w a i t -listed g r o u p , y o u w i l l h a v e y o u r f i r s t E E G a n d t e s t i n r g s e s s i o n , a n d
4 mon th s you wi ll en ter in to th e s eq u en ce as d etailed ab ove.
T h e m a i n c o l l e c t i o n s o f d a t a w i l l b e c o m p o s e d o f -a p a n p d e -p r en ci l tes t res u lt s ab ou t h ow you
are feel in g an d cop in g, b lo od s amp les to mon itor you r s tres s le vels an d a b rain wa ve s tu d y.
A l l p a rt ici p an ts wi ll b e as k ed to give b loo d s amp les (2 0 mls ) an d fill ou t q u es tion n aires b oth
a t t h e b e g i n n i n g o f t h e -u p ( a p t r 6 m o j n t h e s ) c f o t r f , u r t h e a r t t h r e e m
h o r m o n e a n d i m m u n e a n a l y s i s . T h e m e a s u r e m e n t s w i l l i n c EE l G u d e f o r s o m e o f y o
(electr oen cep h al ograp h ) wh ich rec ord s th e electrical activit y of on e’s b rain . Th is is a
c o m p l e t e l y -in n vas o n ive p roced u re, wh ich in volves th e attach m en t of va riou s elect rod es to
y o u r h e a d u s i n g a c a p a n d s o m e g e l . P l e a s e n o t e t h a t t h e ced e l on e c t th r e o sd ue rface s a r e p l a
of th e s ki n on l y an d th ere is n o d an ge r o f electric s h oc k.
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 21 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Fo llowi n g at tach men t o f th e elect rod es , you will b e s eated in fr on t of a c omp u ter mon itor an d
i n s t r u c t e d t o d o c e r t a i n t a s k s s u c h a s r e m e m b e r i n g s o m e on th w o e r d s a n d f a c e s p r
comp u ter s cre en . Th ere wi ll b e th ree E E G rec ord in g s es s ion s s p read th rou gh ou t a wh ole
p eriod of th e s t u d y ea ch las ti n g ab ou t two h ou rs . All d etails an d d ata res u ltin g fr om th e s tu d y
will remai n s tri ct l y c on fi d en ti al.
T h e t w o s e t s o f t r a i n i n g a r e in S e l f-H yp n o s i s a n d J o h r e i :
Self-Hyp n os is : H yp n os is is an alte red s tate of con s ciou s n es s th at can feel like d eep relaxati on
d u rin g wh ich a p ers on can u s e th eir imagi n ation in a p owerfu l wa y. Se veral res ea rch
s t u d i e s h a v e s h o w n t h a t m a n y, a l t h o u g h n o t a l, l p e op le can con tr ol th ei r p ain an d af fect
th eir emot i on s , an d even al ter th eir i mmu n e s ys te ms , d eter min ed b y h ow th e y u s e t h e
h yp n oti c s tat e. On e recen t s tu d y b y D r M ich ael An ton i of th e Un iv ers it y of Mia mi
s h owed th at p at ien ts wi th HIV h ad , on a v erage , a b etter q u alit y of life, an d in d eed , man y
p o s i t i v e l y a f f e c t e d t h e i r i m m u n e s y s t e m w i t h a g r o u p p r o g r a m m e i n c l u d i -h n yp g s ne os l f is ,
s imilar t o th e on e we p lan for th os e of yo u ran d oml y as s ign ed t o th is arm o f th e s tu d y.
W e t h i n k t h a t s u c h a p r o g r a b e m pm rop e erl s h y o tu es l ted d h ere in Lon d on . If you a re
as s ign ed to th e h yp n os is c on d ition , you w ill firs t e xp erien ce h yp n os is , th en learn h ow to
u s e s e l f-h yp n os is . Va ri ou s p os s ib le goa ls will b e d is cu s s ed an d you will b e tau gh t h ow
t o u s e s e l -h f y p n o s i s f o r a t l h s e y o g u o c h o o s e . Y o u w i l l b e a s k e d t o p r a c t i c e y o -u
r s e l f
h yp n os is d ai l y d u ri n g th e p roject .
J oh rei : J oh rei is a J ap an es e h ealin g meth od . An yon e c an learn to d o J oh rei afte r
u n d ers tand in g th e core p ri n cip les an d b asic tech n iq u es . Healin g m eth od s h ave m an y
variati on s an d J oh rei is b as ed on th e con cep t of ‘h ealin g on es elf b y h ealin g oth ers ’ u s in g
a n o n-t ou ch in g met h od . J oh rei h as ju s t b egu n to b e s cien tificall y t es ted with s ome
e n c o u r a g i n g r e s u l t s . M i l l i o n s o f p e o p l e a r o u n d t h e w o eir r l d u s e J o h r e i t
h ealth , in cl u d in g p eop le wi th HIV. Du rin g you r ti me in th e p roject , yo u will lea rn t h es e
tech n iqu es . J oh rei is s ai d to reli eve s ymp t oms , even th ou gh s o me p e op le fo r a d a y or s o
a s t h e y l e a r n t h e t e c h n i q u e s c a n e x p e r i e n c e b r i e f , m i n o r d i s c o m mild f o r t s u c h a s
s ymp toms of h ead ach e, s weatin g or d iarr h oea, alth ou gh we h ave s een n on e of th is h ere in
ou r p revi ou s s t u d i es . Du ri n g t h e p roject , you will b e as ked t o p ractis e J oh rei ev er y d a y
with s omeon e (p art n er, d au gh ter, frien d e tc.).
I f y o u a g r e e t o ate, p a you r t i wi c li l p b e on e of 1 5 0 p eop le like you rs elf with d iagn o s ed HIV
wh o wi ll b e in vi ted to p art ici p at e in th e p roject. You , alon g with th e oth ers , will co mp lete
v a r i o u s t e s t s , a n d w i l l h a v e -wa y o ves u r ) meas E E G u red ( b . r Ya ou i n wi ll h ave th es e tes ts at
th e b egi n n in g, an d agai n at fou r - fi ve mo n th s for a r ep eat s et o f tes ts . Howe ver, yo u will
meet re gu larl y in a grou p o f 6 - 9 o t h e r s t u d y s u b j e c t s i f y o u a r e a s s i g n e d t o l e a r -n
s e l f
h y p n o s i s o r J o h r e i . I n s -h e l y f p n o s i s , t h e g r -o o r u d p i n a c t o r w i l l b e D r T a n n is Lai d law, a
p s ych ol ogi s t wi th e xt en s ive e xp eri en ce in clin ical h yp n os is . If you a re in th e J oh rei gr ou p ,
yo u wil l b e t rai n ed b y Dr Akira Nai to , a d octor t rain ed in b oth wes tern med icin e a n d th e
J oh rei h eal in g met h od . If you are in th e w aitin g lis t gr ou p , you will b e ran d oml y as s ign ed to
e i t h e r J o h r e i o r s e -h l f y p n o s i s i mn on 3 th s ti me wh en you wi ll j oin with oth ers in th e train in g.
All th e b rai n wa ve s tu d ies will b e with D r P rab u dd h Dwived i, wh o is a clin ical p s ych olo gis t
w i t h s p e c i a l i s e d k n o w l e d g c e t i n g o f E E c G o n s d t u d i e s . T h e S -h e l yp f n os is , J oh r ei an d
EE Gs wi ll b e p erf or med at th e C h arin g C ros s Hos p ital.
Self-h yp n o s i s o r J o h r e i s c h e d u l e :
I f y o u a r e i n e i t h e r o f t h e -h s e yp l f n os is or J oh rei g rou p s , you will meet t ogeth er wit h th e
o t h e r p a r t i c i p a n t u r s a g r n d o u p y -o o c rd o in at or on e s es s ion a week f or fou r w eeks ( 1 to 4 on
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 22 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
t h e d i a g r a m a b o v e ) . Y o u w i l l l e a r n -h s e yp l f n os is or J oh rei in ord e r to b egin p ractic e at h om e.
A s mall d ai l y d iar y wi ll b e creat ed s p ecifi call y f or you , to b e filled ou t at th e en d o f each d a y
(takin g ab ou t 2 mi n u tes ) an d kep t fo r th e d u ration of th e p roj ect.
Aft er th is m on th of w eekl y meetin gs , th e s h orter m eetin gs will b e s p aced at on e me etin g a
mon th fo r th e d u rat ion o f th e p roj e ct, an d you a re welc om e to con tin u e p as t you r fi n al
a s s e s s men t p oi n t . Al t oget h er , you will h a ve th ree tes tin g s es s ion s for EE G an d two fo r
p s ych ol ogi cal tes ti n g, las ti n g ab ou t 2 h ou rs . Th e tes tin g is for th e p u rp os e of m on itorin g you r
p r o g r e s s a n d y o u r r e s p o n s e t o s e -h l f y p n o s i s o r J o h r e i . W h e n y o u artmen a t t e n t d on o u r d e p
t h
t h e 1 0 floor of th e med ical s ch o ol f or yo u r EE G tes tin g you will h ave p len t y of ti me to fill
ou t th e p s ych ol ogi cal tes ts . Th e y are n o t on erou s an d th ere are n o ri gh t o r wr on g an s wers ,
alth ou gh you r op in ion wi ll b e s ou gh t ab o u t man y d iffe ren t as p ects of you r exp erie n ce.
As s es s men t ti mes in vol vi n g p s ych ol ogica l tes ts an d EEG are in d icated b y th e a rro ws lab elled
1 ,2 an d 3 .
W h a t d o I h a v e t o d o ?
T h e r e a r e n o l i f e s t y l s. e N r o e s ps et ci r al i ch c t an i ge o n is req u ired f or th is s p ecific s t u d y in you r
l i f e s t y o l t e h e r t h a n i n c o r p o r a t i n g i n t o y o u r d a i l y s c h e d u l e s o m e t i m e t o p r a c t i c e -y
o u r s e l f
h yp n o s i s o r J o h r e i.
W h a t i s t h e d r u g o r p r o c e d u r e t h a t i s b e i n g t e s t e d ?
You wi l l n ot b e gi ven an y d ru gs in ad d ition to you r u s u al med icati on s .
W h a t a r e t h e a n l a t e i r v e s f o r d i a g n o s i s o r t r e a t m e n t ?
You s h ou l d feel fre e t o as k you r GP ab ou t you r d iagn os is an d an y altern ative treat men t fo r it.
W h a t a r e t h e s i d e e f f e c t s o f t a k i n g p a r t ?
W e e x p e c t n o s i d e e f f . e c t s
W h a t a r e t h e p o s s i b l e b e n e f i t s o f t a k i n g p a r t ?
W e hop e t h at b o t h i n t erv en t i on s will h elp you . Howe ver , th is can n ot b e gu aran teed . Th e
in format i on we get fro m t h i s s tu d y ma y h elp u s to b etter treat fu tu re p atien ts with HIV.
W h a t i f n e w i n f o r m a t i o n b e c o m e s a v a i l a b l e ?
S o m e t i m e s d u r i n g t h e c o u r s e o f a r e s ce h a r p roj ect n ew in fo rmat i on b ecom es avail ab le ab ou t
th e treat men t / d ru g th at is b ei n g s tu d ied . If th is h ap p ens , you r r es earch d oct or wil l tell you
ab ou t it an d d is cu ss wi th you wh eth er yo u wan t to con tin u e in th e s tu d y. Y ou m a y d ecid e to
w i t h d r a w b u t u di ecid f e y o to con ti n u e in th e s tu d y yo u will b e as ked to s i gn an u pd ated
con s en t for m.
Alte rn at ivel y, on recei vi n g n ew in fo rmati on you res earch d oct or mi gh t con s id er it t o b e in
y o u r b e s t i n t e r e s t s t o w i t h d r a w y o u f r o m t h e s t u d y . H e / s h se o nw s i an l d l e x p l a i n t h e r e a
arran ge fo r you r ca re t o c on tin u e.
W h a t h a p p e n s w h e n t h e r e s e a r c h s t u d y s t o p s ?
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 23 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
T h e i n t e n s i o n i s t h a t y o u w i l l b e i n d e p e n d e n t i n y o -h u r yp s ne os l f is an d J oh rei s ki l ls an d will
n o t n e e d f u r t h e r i n s t r u c t i o n . H o w e v e r , a l i s t o f q u a l i f i e d p r a c s t in i t i Lon o n e dr on can b e
mad e avai lab le t o you on co mp letion o f t h e s tu d y.
W h a t i f s o m e t h i n g g o e s w r o n g ?
If ta kin g p art in th is res ear ch p roject h ar ms you , th ere a re n o s p ecial c o mp en s ation
a r r a n g e m e n t s . I f y o u a r e h a r m e d d u e t o s o m e o n e ’ ma s y n he ag vl e i gr g ou e n nc de s , t h e n y o u
for legal act ion b u t you ma y h ave t o p a y f or it. R egard les s o f th is , if you wis h to comp lain
ab ou t an y as p ect of th e wa y you h ave b ee n ap p roach ed or treat ed d u rin g th e cou rs e of th is
s t u d y , t h e n o r m a l N H S c o m p l a i n t s m e c h a n i s m ilab s m le a y t o b yo e u . a v a
W i l l m y t a k i n g p a r t i n t h i s s t u d y b e k e p t c o n f i d e n t i a l ?
All in f or mat i on t h at i s c ol l ected ab ou t yo u d u rin g th e cou rs e of th e res earch will b e kep t
s trictl y c on fi d en t i al . Al l i n for mation ab ou t you will b e kep t s ecu rel y at Imp erial C ollege,
C h arin g C ros s Hos p i t al , Lon d on , an d u n der p ers on al s u p ervis ion of th e r es earch ers wh en
b ein g tran s p ort ed fro m C h el s ea & Wes tm in s ter Hos p ital to C h arin g C r os s Hos p ital .
W h a t w i l l h a p p e n t o t h e r e s u l t s o f t h e r e s e a r c h s t u d y ?
T h e r e s u l t s o f t h i s s t u d y a r e in ten d ed to p rovid e n ew in f or mation ab ou t th e tr eatme n t of
p eop le wi th n ewl y d iagn os ed HIV , an d will b e p u b lish ed as acad emic p ap ers in p rofes s ion al
jou rn al s . It wi ll b e th e b as is of talks at c on feren ces ar ou n d th e world . No n ames or oth er
i d e n t i f y i n ects g a of s p th e p art ici p an ts wi l l b e d is clos ed d u rin g an y of th es e c om mu n ication s .
W h o i s o r g a n i s i n g a n d f u n d i n g t h e r e s e a r c h ?
Th is res earch i s s p on s ored b y th e or gan is ation th at teach es J oh rei in J ap an . It is or gan is ed b y
th e Dep t . of C ogn i t i ve Neu ros cien ce an d Beh avi ou r, Imp erial C ollege Lon d on .
W h o h a s r e v i e w e d t h i s s t u d y ?
Th e R i vers i d e R es earch Et h i cs C o mmitte e revi ewed th e s tu d y.
C o n t a c t f o r f u r t h e r i n f o r m a t i o n
Dr Tan n i s Lai d l aw can an s wer an y fu rth e r q u es tion s on 0 2 08 8 46 7 04 2 or email :
t . l a i d l a w @ i c . a c . u k
Th an k you fo r con s i d eri n g t a kin g p art in ou r res ea rch p roject. P leas e take th is in fo rmation
s h eet h ome wi t h you .
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 24 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
T i t l e o f P r o j e c t :
P A R T I C I P A N T C O N S E N T F O R M
T h e E f f e c t s o f T w o P s y c h o l o g i c a l v e I n t i e o r n T e c h n i q u e s , S e -Hyp l f no si s
a n d t h e J o h re i He a l i n g M e t ho d , o n Q u a l i t y o f L i f e , P sy c ho l o g i c a l W e -B l l e i ng ,
E E G m easure s a nd Va ri o us Imm unol og ic al M ea sures i n HIV: A Ra ndoml y
C o nt rol le d Pi lo t St udy .
( T h e p a t i e n t / v o l u n t e e r s h o u l d c o m p l e t e t h e w h o l e t h o i f s s h e e t h i m / h e r s e l f )
H a v e y o u r e a d t h e I n f o r m a t i o n S h e e t ?
Y e s N o
H a v e y o u h a d t h e o p p o r t u n i t y t o a s k q u e s t i o n s a n d d i s c u Y s e s t h N e o s t u d y ?
H a v e y o u r e c e i v e d s a t i s f a c t o r y a n s w e r s t o a l l o f y o u r Y q u e s e s t i N o n s ?
H a v e y o u r e c e i v e d e n o u g h i n f m o r a t i o n a b o u t t h e s t u d y ?
Y e s N o
W h o m h a v e y o u s p o k e n t o ? ( w r i t e n a m e ) _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
Do you un d erst and t ha t you a re free t o wi t h d ra w from th e st ud y,
a t a n y t i m e , w i t h o u t h a v i n g t o g i v e a r e a s o n , a n d w i t h o u t a f f e c t i n g
t h e q u a l i t o y u r o f p r e y s e n t o r f u t u r e m e d i c a l c a r e ? Y e s N o
D o y o u a g r e e t o t a k e p a r t i n t h i s s t u d y ?
D r T M L a i d l a w
D e p a r tme n t o f C o g n itiv e
N e u r os c ien c e & Be h a v io ur
Fa c u lty o f Me d ic in e
Imperia l C o lle g e o f Sc ie n c e ,
T e c h n o l o g y a n d M e d i c i n e
S t D u n s t a n ’ s R o a d
L O N D O N W 6 8 R P
Y e s N o
I u n d erst an d th at th e Loc a l Et hi c s C ommi tt ee ma y r evi e w t h i s form a s p a rt of a
mon i t orin g p roc ess.
N A M E I N B L O C K L E T T E R S :
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
C o n t a c t s : A d d r e s s : _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
T e l e p h o n e n u m b e r ( s ): _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
E m a i l : ___ ___ ___ ___ ___ ___ ___ ____ ___ ___ ___ ___ ___ ___ ___ _
S i g n a t u r e : _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ t e: D a ___ _ / ___ __ / ____ ___
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 25 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Appe ndi x 2 : P s y c h o l o g i c a l t r a i n i n g i n t e r v e n t i o n p r o t o c o l s
1. S e l f h y p n o s i s t r a i n i n g
S e s s i o n p l a n s
In s t r u c t o r ma n u a l ( w i t h c s r i p o f s e l -h f y p n o s i s f o r -r a u e d c i o r o d i ) n g 230
2. Johr e i t r a i n i n g
C o u r s e d e s c r i p t i o n
O n e -h ou r In t r o d u c r t y o S e m i n a r P o w e r p o i n r t e s e P n t a t (wi i o tn h n ot es:
a s a n e x a mp l e o f , e x t r a c t f r o m , t h e e x p l a n a t i o n i n t h e J o h r e ti ra in in g
s e s s i s) o n
256
J o h r e i H a n d b o o k
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 26 - I m p e r i a l o C n o d l o n l e g e L
227
253
272

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
D r . T a n n i s M. L a i d l a w
I m p e r i a l C o l l e g e L o n d o n
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 27 - I m p e r i a l o C n o d l o n l e g e L

P s y c h ol o gi cal in ter ven ti on an d p s y c h o-n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
S e l f-h y p n o s i s G r o u p
S e s s i o n 1 : I n s t a n t R e l a x a t i o n
1 . N a m e t a g s
2 . In tr od u ct i on s of p eop l e i n clu d i n g me.
3 . T o p i c o f t h e D a y : I n t r o d u c t i o n t o h y p n o s i s a n d P N I
- S t o r y o f m y P h D
- S t o r y o f u s i n g h y p n o s i s i n i n f e c t i o n s
- Ima ger y t o b e u s ed
4 . H yp n os i s S es s i on 1 : I n s t a n t R e l a x a t i o n
H y p n o s i s S e s s i o n 1 : ‘ I n t r o d u c t i o n ’
T h e H y p n o s i s P r o c e d u r e : ‘ T h e B e a k e r D i a g r a m ’
S e s s i o n 2 : V i e wi n g t h i n g s d i f f e r e n t l y t o r e g a i n c o n t r o l
5 . D e -B u g g i n g N e g a t i v e T h o u g h t s R e c o r d
6 . H yp n os i s S es s i on 2 : ‘ S y m b o l ’
S e s s i o n 3 : B r e a t h i n g y A w n x a i e t y a n d P a n i c
7 . T h e F e e d b a c k L o o p o f N e g a t i v e T h o u g h t s
P h y s i o l o g i c a l R e a c t i o n s t o S t r e s s
M u s c l e s b e c o m i n g t e n s e o r w e a k
S o m e C a t a s t r o p h i c T h o u g h t s
T h e B r e a t h i n g T r i a n g l e
8 . H yp n os i s S es s i on 3 : ‘ S h a r k s ’ n ’ B a t s ’
S e s s i o n 4 : Ge t t i n g r i d o f p e s k y t h o u gh ts
9 . Step-b y -s t e p I n s t r u c t i o n s f o r t h e I n t e r r u p t D i s t r a c t i o n P r o c e d u r e
1 0 . H yp n os is S e s s i o n : ‘C 4 o a s t l i ’ n e
P o s t -t r a i n i n g T r a c k s : T o p r o v i d
1 1 . H y p n o s i s P o s t T r a i n i n g
S e s s i o n s :
5 : ‘ B l u e ’
6 : ‘ B e a c h ’
7 : ‘ T h r u g m u t t o n ’
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 28 - I m p e r i a l o C n o d l o n l e g e L

C o u r s e d e s c r i : p Dt a i l y o Jn o h r e i L ( a y i n g-o n -o f -h a n d s �l i k e he a l i n g m e t h o d ) C o u r s e
L e n g t h o f c o u r s e : 4 w e e kl y t r a i n i n g + s 3 m o n t h f /u A c c o m m o d a t i : o n I m p e r i a l C o l l C e h g e a r i n g C r o s s C a m p u s
Av a i l a b i l i t y :
W e d n e s d a y s h 2 o u r s ( 1 8 : -2 3 0 : 3 0 ) E n try : T h o s e w h o a g r d e e with a c o n s e n t f o r m
B o o k : H a n d o u t s T u t o r’s c e r t i f i c : a t Je oh rei in s tru ctor, Ad u lt teach in g, M.D .
Progression:
1 . S t r e s s m a n a g e m e n t t o o l s
2 . P r a c t i s i e t h n o d g a s h a e d a i a l l y h i e a n l t g h m a m i n t e n a n c e t e c h n i q u e
Study details:
J oh rei is a h ealin g meth od wi th th e con ce p t of ‘h e a l o n e s e l f b y h e a l i n g o ’ t f h o e r s e l f-care o r m ain tain in g h eal th & h ap p in ess .
S t u d y i n g t h e s u b j e c t p r o v b od i y in d de ail s y life. a w a y f o r y o u t o b a l a n c e y
You will fin d s ome ap p licat ion s of J oh rei fo r you r d ai l y li fe in th is cou rs e.
The study-subject can be divided into tw o parts:
1 . Th e s tu d y of Dail y J oh rei , in cl u d in g tech n iqu es h ow to p erf orm th e h eal in g met h od in a co mp et en t man n er.
2 . A s tu d y o f th e p h ilos op h y & p ri n ci p les o f J oh rei , l oo ki n g p art icu larl y at th e w a y th e h eal in g p roces s ta kes p lace an d th e s ign ifi can ce o f th es e
mean in gs in real li f e.
Tho s e t w e o l e m e n t s a r e s e e n a s -c i o n n t e r c t i n g . I t p r o v i d e s y o u w i t h a to n ao p ply p o r th t es u n e i tech t y n i qu es & ph il os o ph y in t o da il y li fe.
A i m s a n d O b j e c t i v e s o f D a i l y J o h r e i c o u r s e
Overall
Aims: T o i n t r o d u c e t h e b a s i c c o n c e p t s o f J o h r e i p h i l o s o p h y , p r i n c i p l e s a n d p r a c t i c e
T o p r o v i d e o p p o r t u n i t i e s , e n c o u r a g e m e n t a n e d p articip i n s p an i r ts a to t i ap o pn ly t J oh o rei t h Art of Li vi n g an d J oh rei p ract ice to d ai l y li fe.
T o e n s u r e t h e p a r t i c i p a n t s a r e a b l e t o g i v e D a i l y J o h r e i c o m p e t e n t l y a n d i n s a f �i e m n a n a n e r -p n o rofes n s ion al cap aci t y.
O u t c o m e s : At th e en d o f th e c ou rs e p art i ci p an ts wi ll b e a b l e t o : -
1 . I d e n t i t f h e y b a s i c p r i n c i p l e s a n d c o r e c o n c e p t s o f J o h r e i
2 . G i v e d a i l y J o h r e i c o m p e t e n -p t r l o y f e i s n s i a o n a n l o n c a p a c i t y
3 . State t h e m a i n a s p e c t s c o n c e r n i n g t h e s a f e p r a c t i c e o f J o h r e i
4 . B e a w a r e o f o p p o r t u n i t i e s i n t h e f u t u r e f o r r e i n f o r c i n g a n d f u r ht er u n d ers tan d in g of J oh rei p h il os op h y an d p racti ce.
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Session 1
Ai ms : T o p r o v i d e a n o v e r v i e w a n d p r a c t i c a l i n t r o d u c t i o n t o J o h r e i
O u t c o m e s: At t h e e n d o f t h e s e s s i o n p a r t i c i p a n t s w i l l b e a b l e t o - :
1 . State t h e m a i n e l e m e n t s o a r f d s h J e a l o t h i r e r e l i �( f e 3 a s f o t s u y n l d e a t a i o n , h J o h r l e i i v i e s w t p o i n t c o f i l w l n a e s y s ) t o w
2 . Id e n t i f y h o w J o h r e i m a y b e u s e d i n ( mean d a i l in y g ol f i ‘S f e p i r i t u a ’, l i T t u y n i -i n g , P r a c t i c a l J o h r e i )
3 . D e m o n s t r a t e t h e e s s e n t i a l e l e m e n t s o f J o h r e i a s ( a D d a i l y y p J r o a h c r t n e i q c u e e t s ) e c h
Session 2
Aims: T o in trod u ce th e b as ic p ri n ci p les an d a core p h il os op h y s u p p ort in g J oh rei p ract ice an d it s ap p li cat ion for d ai l y li fe .
O u t c o m e s: A t t h e e n d o f t h e s e s s i o n p a r t i c : i - p a n t s w i l l b e a b l e t o
1 . I d e n t i f t y h e b a s i c p r i n c i p l e s s r u e p i p o p r t a i c t n i g ( s c p e J i r o i h t p r e c e d e s p h y s i c a l , t o x i n s a n d c l o u d s , p r o c e s s o f p u r i f i c a t i o n , I Z U N O M E )
2 . B e a w a r e o f ‘M A K O T O ’ (l o v e , s i n c e r i t y a n ) d as i a n co t re e g cr on i t cep y t of J oh rei p h il os op h y an d p ract ice. 3 . S t a t e t h e f i v e f i n g e r r u l e s o f J o h r e i
4 . R e c o g n i s e t h e b r i e f h i s t o r i c a l b a c k g r o u n d o f J o h r e i a n d a p p r e c i a t e t h e w o r k s o f M o k i c h i O k a d a
5 . B e a w a r e o f t h e i m p o r t a n c e o f i n t e n t i o n s o t h a t t h e y c a n a p p l y v i s u a l i s a t i o n i n t o J o h r e i p r a c t i c e
6 . D e m o n s t r a t e a b a s i c t e c h n i q u e s o f J o h r e i w i t h v i s u a l i s a t i o n
Session 3
Aims: T o p l o e r x e t h e w i d e r a s p e c t s o f J o h r e i p h i l o s o p h y e m b r a c i n g t h e v a l u e o f a r t a n d b e a u t y f o r b o t h i n s p i r a t i o n a n d w e -b l l e i n g
T o e x p l o r e J o h r e i p h i l o s o p h y o f n u t r i t i o n a n d t h e v a l u e o f a l i f e s t y l e i n h a r m o n y w i t h N a t u r e
To en cou r age s tu d en ts to b e aw ar e o f t h e im p o r t a n c e o f s p i r i t u a l c o n n e c t i o n w i t h o u r s e l v e s , o t h e r s a n d N a t u r e
O u t c o m e s: A t t h e e n d o f s e s s i o n p a r t i c i p : a - n t s w i l l b e a b l e t o
1 . R e v i e w s e q u e n c e o f D a i l y J o h r e i t e c h n i q u e
2 . Be aw are of th e wid er as p ects of J oh rei p h il os op h y e mb raci n g th e val u e of a rt an d b e a u t y f o r b o t h i n s p i r a t i o n a n d w e l l b e i n g
3 . Ou t l i n e t h e J o h r e i p h i l o s o p h , y ‘N o a n t u n r u e t r F i a t r i m ’ o i a n n g d t h e n a t u r e
4 . B e a w a r e o f t h e v a l u e o f s p i r i t u a l c o n n e c t S i o p n i r ‘ i t u a l ’ with c o r ou d rs elv es , oth ers an d Nat u re
Session 4
Aims: T o r e i n f o r c e t h e b a s ic p r i n c i p l e s a n d c o r e c o n c e p t s o f J o h r e i, an d th e s afe p ract ice within a n -p o n r o f e s s i o n a l c a p a c i t y
O u t c o m e s: A t t h e e n d o f s e s s i o n p a r t i c i p : a - n t s w i l l b e a b l e t o
1 . P r a c t i c e D a i l y J o h r e i c o m p e t e n t l y w i t h i n t h e h o m e -p r a o n f d e s s w i o n t a h l o c t a ity p h a e c r s i n a n o n
2 . R e v i e w t h e s e q u e n c e o f D a i l y J o h r e i t e c h n i q u e a n d k n o w t h e s e q u e n c e o f S p i r i t u a l J o h r e -J i o & h r e S i e l f
3 . Be aw are of op p ortu n iti es in th e fu tu re fo r rei n f orci n g an d fu rt h er u n d ers tan d in g of J oh rei p h il os op h y an d p racti ce.
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S C H E M E O F W O : R D K a i l y J o h r e i cour s e
C o u r s e : D a i l y J o h r e i h e a l i n g m e t h o d s w i t h b a c k g r o u n d p h i l o s o p L h e i c e s t u r e r : D r . A k i r a N a i t o
U n i t N o / T i t l e 4 u n i t s
Le vel : b e g i n n e r
S e s s i o n T o p i c s ( A i m s ) &
T e a c h i n g m e t h o d s L e a r n i n g As s e s s m e n t R e s o u r c e s K e y-c o n c e p t s
No.
C o n t e n t s ( O b j e c t i v e s )
activities t e c h n i q u e s
1 D a i l y J o h r e i
Facilitating br a i n s t o r m i B n r g a i n s t o r m i O n b g s e r v a t i o n P o w e r -p o i n t J o h r e i
F o u n d a t i o s n of J oh rei phi l o s o p h y P o w e r -p o i n t p r e s e n t a t P i a i o n r w o r k Q & A Wh ite b oard “S p irit p reced es
D a i l y J o h r e i t e c h n i q u e s D e m o n s t r a t i o n P r a c t i c a l G r o u p w o r k
“ R e a l i a ” C D p h y s i c a l ”
Q & A
Q & A
“h eal on es elf b y
G i v e n i n f o r m a t i o n G u i d e d r e ing a d
H a n d o u t s h e a l i n g o t h e ” r s
2 P r i n c i p l e s o f J o h r e i p r a c t i c Facilitatin e g d is cu s s ion D i s c u s s i o n Dis cu s s ion P o w e r -p o i n t “P roces s of
H i s t o r i c a l b a c k g r o u n d P o w e r -p o i n t p r e s e n t a t P i a i o n r w o r k O b s e r v a t i o n Wh ite b oard pur i f i c a t i o n ”
Hi s t o r y o f J o h r e i D e m o n s t r a t i o n P r a c t i c a l G r o u p w o r k
“ R e a l i a “ M ” A K C O T D O ”
P r o c e s s o f P u r i f i c a t i o n
G u i d e d r e ing a d
In ten tion :
Visualisation
Q & A
Q & A Q & S A P O C
“You are wh at
In t e n t i o n G i v e n i n f o r m a t i o n
H a n d o u t s
y o u t h i ” n k
3 A r t a n d B e a u t y
P o w e r -p o i n t p r e s e n t a t G i u i o n d e d r e a d i n O g b s e r v a t i o n P o w e r -p o i n t “P arad is e on
A r t o f N a t u r e
D e m o n s t r a t i o n P r a c t i c a l P a i r w o r k
W h i t e b o a r d
e a r t h ”
“R ealia” C D A p p r e c i a t s i o n
& g r a t i t u d e
N a t u r e f a r m i Q n g & A
Q & A Q & A
Nutrition
S p i r i t u a l C G o i r v d e n i n f o r m a t i o n
H a n d o u t s “ S p i r i t u a l c o r d ”
4 R e v i e w i n g J o h r e i s s e s s i o n P o w e r -p o i n t p r e s e n t a t P i a i o n r w o r k F e e d b a c k P o w e r -p o i n t “ I Z U N O M E ”
S p i r i t u a l J o h r e i
D e m o n s t r a n t P i r o a c t i c a l G u i d e d r e a d i n O g b s e r v a t i o n Wh ite b oard L o v e f o r o t h e r s
S e l f-J o h r e i
Quiz
Quiz
Quiz “ R e a l i a ” C D
Q & A
Q & A Q & A
C e r t i f i c a t i o n f o r a t t e G n d i a v n e c n e i n f o r m a t i o n G r o u p w o r k
H a n d b o o k
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P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
D a i l y J o h r e i
W e l c o m e ! A n d t h a n k y o ming. u f o r c o
I a m ve r y ho no ur e d a nd ha ppy t o be a ble t o ha ve t his opp ort un it y to ta lk t o yo u a bo ut Jo hre i.
Le t me in t r od uce my s e lf , I a m ……
F i r s t t h i n g I w o u l d l i k e t o s t a r t w i t h i s -int a rodu s e l f ct io n se ss ion.
C o u l d y o u s t a t e y o u r n a m e , w h e r e y o u c nd o m what e f r kind o m of a thought has brought you here, in
ot her wo r ds , t he obj e ct ive or ex pec t at io n t o co me t o t oda y’s t a lk br ie f ly, ple a s e ?
W h a t d o y o u w a n t t o t a k e a w a y f r o m T o d a y ’ s s e s s i o n ?
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 56 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Wh a t do you co n si d e r ‘ Spi ri t’ o r
‘ S p i r i t u a l i t y ’ i s ?
&
W h e n d o o u y t h i n k a b o u t i t ?
B r a i n s t o r m i n g !
Hi g h sp i ri t , lo w sp i r i t, mean sp i r i t , t eam sp i r it … . .
F i r s t o f a l l , it h t his I br a in w o s tor u ming l d s e s sl ion. i k e t o s t a r t w
I n Bra in s to r ming, t her e a r e no r igh t or wr on g a ns we r s .
P le as e disc uss in the gr oup t ha t wh a t do yo u co ns id e r ‘s pir it ’ or ‘s pir it ua lit y’ t o be ?
B y t h i s I m e a n , w h a t s o r t o f t h i n k i n g c o m e s t o y o u r m i n d w h e n y o u h e a r d t ‘s h pir e w it o ’ r or ‘s pir it ua lit y’.
Do you ha ve a ny de f init ion a bo ut t hes e ?
A n y d i f f e r e n c e b e t w e e n ‘ s p i r i t ’ a n d ‘ s p i r i t u a l i t y ’ ?
T he n ne xt qu es t ion is whe n do yo u t hin k a bou t th e c on ce pts of ‘s pir it ’ or ‘s pir it ua lit y’, in ot her wo r ds ,
w h a t s o r t o f s i t eu s a you t i o tn hin m k a t he k s e ?
Ar e you a l wa ys t hinkin g of t hes e ? Or yo u have ne ve r t hou gh t of t he se ?
Y o u s u r e l y k n o w t h e w o r d , s o a t l e a s t o n c e y o u h a v e , h a v e n ’ t y o u ?
A n y i d e s a ple a se .
An yt hin g yo u ma y t hink of wou ld be ve r y he lp f ul a nd use f ul for us .
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P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
T h r e e w a y s i n w h i c h t o a t t a i n s p i r i t u a l a w a r e n e s s
B e a u t y
S p i r i t u a l P r a c t i c e
Life Challenges
This s lid e is a summa r y of wha t I ha ve he ar d f r om pr e vio us gr ou ps of t he s itu at io ns wh e n th e y ma y t hin k
of the sp ir it or s pir it ua lit y. The se ar e t yp ic a l e x a m p l es of t h e wa ys t o be a wa r e of sp i r i t i n Jo h r e i as we l l.
Li f e c h a l l e n ge s i n c lude whe n yo u a re s uf fe r ing s ome t hin g dif f ic ult l i k e a t t gding e n f un e ra ls or e mot iona lly
d r a i ing n t ime . Sp ir it ua l pr ac t ice i n c l e u s d w o r s h i p , m e d i t a t i o n , a n d s . p i r i t u a l h e a l i n g
I n J ohre i t his ‘B e a u t ’ y i s h i g h l y e m p h a s i z e d a n d i t i n c l u d e s a p m i a e s c t e e r o p f i e a c r e s t i n l i w k e h i you c h
m a y find a s pir it of an ar t ist , a nd s o m e w h e r e w be i t aut h if ul sc e ne r y in which you m a y f e e l yo ur s pir it is
uplif t e d.
A s y o u h a v e r a i s e d a n d h e a r d f r o m ’ o t hough h e r s t s ab out ‘s p i r i t ’ and ‘s p i r i t u ’, a l t her i t e y ar e qu it e a lot of
me a nin gs or co nce pts you c ould t hin k wh e n yo u he ar t hes e wo r ds . T he pur pos e of ha vin g t his br a in
s t or min g wa s t hat I would li ke yo u t o kn ow t ha t t he s pir it is not ve r y mu c h fa r f r om e ve r yd a y lif e nor f or c e rt a in sp e c ia l people only.
I t i s , i n a w a ve y , r yone f o r of e us in e ve r yda y lif e . I t is in ‘a n y t i m e a n d a n y w h e r e f o r ’ a n y o n e
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P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Mokichi Okada
1882-1955
Healing and
Spirituality
f o r A L L
T his is a p ict u re of M okic hi Oka d a , a f o u nd e r o f Jo h re i.
T he me ss a ge h e ha d t r ie d t o c on ve y wa s t h at a s s p ir it u a lit y is f or a ll, h e a lin g o r a bilit y t o he a l o t he r
pe ople is a lso f or a ll. J ohr e i is on e of a p ra c t ica l a n d ef fe ct ive a p plic a t io n of an d a t a n gib le e x a mp le of
r e a lis at io n o f wha t you ma y s e e t h e f ut u re in th is e mp o we r in g me s s a ge .
I t is a lwa ys e mpha s is e d in Johre i ph ilo s op hy th a t “E V E R Y O N E F YOU O C AN AP P LY JOHREI t o
AN Y T H I N G a t AN Y T I M E an d AN Y WH E R E yo u wa n t”.
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P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Johrei
P u r i f y i n g o u r s p i r i t a n d u p l i f t i n g o u r s o u l
T h e w o r d ‘ J O H R E I ’ i s i n J a p a n e s e a n d c o n s i s t s o f t h w and o C Rei. h i n e s e c h a r a c t e r s , J o
T h i s l i t e r a t e l y m e a n s p u r i f y i n g t h e s p i r i ur t s oul. a n d J ohr i em i p has l i a e lot s of u p fa l ci et f s t , si o n I g o
would l ike t o in t r oduc e t he m on e by on e .
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P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Maintaining health and happiness in a family
Home practice
D a i l y J o h r e i p r a c t i c e
T he J oh r e i pr ac t ic e is a da ily e xe r c is e like me dit a t io n , j oggin g or wa l kin g.
T he pur pos e of J ohre i pr ac t ic e, a ma in ob je c t ive in t he tr a in in g workshop i.e. learning why and how to
pr a ct is e J ohr e i, is t o ma inta in hea lt h an d hap pin e s s in fa mily a nd f r ie nds , in ot her wo r ds , t o c r ea t e “a
b e t t e r a n d b e a u t i ” f u f rl om w yo o r ur l ed nvir onme nt .
B y t h i s I m e a n t h a t t o b e c o m e c o n f i d e n t a n d c o m c t f i o r s t e a b J l o e h r t e o i p r w a i t -pr h i of n e ss a io nn a l o n
c a pac it y.
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P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
S u p p o r t i n g p e o p l e w h o s u f f e r
I n a ddit io n , s inc e Johre i his t or ic a lly b e ga n a s a t he r ap e ut ic ac t , yo u ca n s u p p ort fr ie n d s a n d f a mily wit h
J ohre i wh e n t h e y a re suff e r ing fr o m s o me t ough c o n d it io n s a s we ll.
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P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
M u t u a l H e a l i n g
‘ H e a l i n g o n e s e l f b y h e a l i n g o t h e r s ’
T his is t he c en tr a l c onc e pt on wh ic h J o h re i p hilo s o p h y a n d p ra ct ic e is ba s ed .
I t is not j us t givin g or r e ce iving h e a lin g. I t is a mu t ua l p r oc e ss .
‘Y o u c a n h e a l y o u r s e l f b y h e a l i n g ’ o t h e r s
H e n c e y o u c a n p l a y a r o l e t i n �‘a g c r e b a e t t e r a n d b e a u t i ’. f u l w o r l d
A c ouple of people is t he s ma lle s t un it of th e s oc ie t y.
Ha ppine ss a nd hea lt h ca n be re a lis e d an d sp r ea d fr om th is s ma lle st un it wit hin f a mily a nd fr ie nd s t o lar ge r
unit s , s a y c ommunit y, s oc iet y a nd ult ima t e ly a ll t he wo r ld . T his pr oc es s is c a lle d by J ohr e i c r ea t in g
‘P a r a d i s e o n ’: E a r be t tt h er an d be a ut if ul wor ld - - f ir s t pe rs on a lly a nd e ve nt ua lly a s a c ommu nit y.
T h i s r ea l i s a t i o n ca n be ac h i e ve d t hr o u gh Jo h r e i p r a ct i c e it s e l f , a n d a l s o t h r o u gh t an gi b l e p r a c t i ce o f he o t r
t e net s of J ohr e i philos ophy.
I n or der to p ra ct is e Johre i e ff e ct ive ly a n d t o en j o y J o hr e i th o r ough ly, a p pr e c iat io n s a n d
a c knowle d ge me nt s of t his Johre i p h ilo s o p h y is ve r y imp o r t a nt an d a ls o e nc o u ra gin g.
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T h r e e f o u n d a t i o n s o f J o h r e i � p h i l o
- Ap p reci at i o n wi th g rat i t u d e in a d ai l y l i f e -
A r t o f H e a l i n g
A r t a n d B e a u t y
A r t o f N a t u r e
T h e J o h r e i p h i l ophy o s c ons is t s of t hr e e f ounda t io ns a s yo u ca n se e he re :
Ar t of He a lin g whic h is J ohr e i pr a ct ic e its e lf , a nd e mph a s is in g t he imp or ta nce a nd a ppr ec iat io n of ‘Ar t
a n d B e a u ’ t and y ‘A r t o f N a ’. t u r e
I n J ohre i, it is e mpha s is e d t ha t t o be a wa r e of t hes e id e a l ult ima t e go a ls is ve r y imp or ta nt , bu t it a ls o is
e qua lly imp or t a nt to ma ke one s te p t owa r ds th e go a ls . I n oth e r wo r ds , yo u ar e en c our a ge d t o part ic ip a te in
t a n g i b l e a c t i v i t i e s o f t h e J o h r e i p h i l o s o p h y i n a l l a s p e c t s i n e v e r y d a y l i nt, f e f r o m y o u r o w n e n v
whic h me a ns t o s ta rt cr e at ing “a b e t t e r a n d b e a u t i .” f u l w o r l d
De t a ils of t he s e ta ngible a c t ivit ie s a re c ove red in t he tr a in in g wor ks ho p . I n th e t r a inin g wor ks ho p , f ir st
A r t o f h e a l i n g i s t h e m a i n o b j e c t i v e t o l e a r n a n d t at o ions a p p will l y be b u touc t he t h d e o t h e r t w o f o u n d
u p o n f o r f u r t h e r u n d e r s t a n d i n g o f f i r s t A r t o f h e a l i n g , s i n c e t h e s e t h r e e p h i l o s o p h i e s -c a onne r e i n ct t in e r g
wit h e a ch ot her .
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P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
T his is a br ie f int r oduct ion a nd o ve r vie w o f J o h r e i.
Do you have any questions a b o u t i t ?
Now, if s ome one as ke d you “Wh a t i s J o h ”, r e i w ? h a t w o u l d y o u t e l l t h e m ?
Suppos e I wa s t he per s on who as ke d yo u wh a t is J oh r e i.
T e ll me a bo ut it .
What would you say to me?
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P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
H e r e a r e t h e s u m m a r i s e d k e y s door t o of yo o p ue r n Johre t h i e xper ie nce wh ic h yo u wi ll b e c ove r in t he t r a ining wo r ks hop.
T hr e e f ou n d at ions of J ohr e i philo s o ph ie s , wh ic h I h a ve a lr ea d y gi ve n t h e t it le s .
T hr e e r eq u ir e ments to st a rt pr ac t is in g o r t o get re a d y t o J o hr e i.
F i v e p r i n c i p l e s i r n t o o pr r ac d e t is e J ohr e i pr ope r ly.
K e y o b j e c t i v e s
Three foundations
Three requirements
Five principles
(Five fingers rule)
Fi ve f in ge r r u le s for me mor is in g a n d re min d in g wh a t t he ke y t h o u ghts a re wh e n yo u pra ct is e J ohre i.
P l e a s e s t a r t e x p l o r i n g t h e s e d e t a i l s i n t h e t r a i n i n g s e s s i o n , s h a l l w e ?
T o d a y , I w o u l d l i k e t o s h o w y o u j u s t t h e t of i t hose l e n a am nd e s wa nt you to tr y t he f ir st ste p of J ohr e i
e x p e r i e n c e , n a m e d a s -in. T u n i n g
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I n or der to pra ct is e Johre i, t he re a re on ly t hr ee r eq uir e men t s.
You are encouraged to hold your doubts if you have any, so you do not have t o BELI EVE th e s e t wo , bu t
p l e a s e T R U ST t he s e a s yo u ca n t r us t s o m eo ne e ve n yo u c a n n ot t r u l y b e l i e ve t h e m -) ; .
T he t wo a re 1 . Tr ust t he powe r o f t he LI GHT , a n d 2 . t he ABI LI T Y o f yo ur se lf .
Y o u a r e q u i t e a l l r i g h t t o f e e l t h a t y o u c a n n eo lf t rt ight r u s nt ow, y o u but r s I a m s ure that yo u c a n t ru st th e
ABI LI T Y of your s e lf if you ar e wis hin g t o be or ma kin g s ome ef f or ts to wa r ds yo ur id ea l se lf .
Do not ign or e your ne gat ivit ie s bu t f oc us mo re in t o t he ot he r s id e r a th er t ha n co nce ntr at in g on ne ga t ive s .
T h is is no t ign or ing, hiding f r om or e ve n de nyin g t ha t yo u ha ve do ubt s . I t is j us t wa it in g f or t he r ight t ime
t o dea l wit h t he m.
T h e n e x t r e q u i r e m e n t i s t h e i n t e n t i o n t o c h a n n e l t h e -c J ao lle h r d e ‘tuning-in i , a n d ’. t h e f i n a l o n e i s
M et a p ho r i c a l l y s p e a king, t he s ou r ce of th e lig h t ke e p s s en d in g t h e LI GHT like a r a dio st at io n .
Li ke a r a d io o r a T V, t her e a re a lwa ys wa ve s b u t yo u ca n n ot se e n o r s e ns e .
M okic hi Oka d a s a id t ha t e ve r y o n e of us h as go t a n a nt en n a t o r e ce ive it .
Once you have tuned it in the r igh t c h a nn e l, th e n yo u wil l b e a ble t o pra ct is e Jo h re i a s on c e yo u t u n e d a
T V t uner in a r ight c ha nne l t he n yo u c a n ge t b e a ut if u l s ou n d an d pict u re . I t c o n st an t ly f lo ws .
T his is it .
Three requirements for practice
• TR US T (although you do not have to believe if you practise)
– i n t h e p o w e r o f t h e s o u r c e o f L I
– i n t h e A B I L I T Y o f y o u r S E L F
• I N T E N T I O N t o c h a n n e l t h e J O H R E I
• T U N I N -I G N w i t h a p p r e c i a t i o n
Wh e n yo u a r e c o m f o r t a b l e t o a c ce p t t he s e t hr e e r e q u i r e m e n t s , i t i s me t i whe n yo u c a n pr ac tis e J ohr e i.
I t is ve r y imp ort a nt to be c omf ort a ble yo ur s elf t o be gin wit h , s o ma ke s ur e t ha t yo u ar e c omf ort a ble
enough.
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P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Five principles for Johrei practice
‘ T o x i n s ’ a n d ‘ C l o u d s i n t h e s p i r i t ’
T h e p r o c e s s o f ‘ P u r i f i c a t i o n ’
‘ I Z U N O M E ’
‘ S p i r i t ’ p r e c e d e ‘ P h y s i c a l ’
‘ S p i r i t u a l C o r d ’
N e x t , I w o u l d l i k e t o s h o w a s u m m a r y o f c o r e p r i n c i p l e s f o r J o h r howing e i p r a c t it t le i c ne a me b y s s .
T he s e a re th e cor e f ive pr inc iple s o f J o hr e i p ra c t ice .
Ea c h will b e c ove r e d in det a il in t he tr a in in g s e s s io n .
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P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Five Fingers Rule
Thumb (T) TUNING IN the source / your self
Index Finger (I) INTENTION and inspiration
Middle Finger (M) Middle way & balance (IZUNOME)
Ring Finger (R) Relax so that you can ENJOY!
Little Finger (L) Let the LIGHT flow
Open palm and receive gratitude with appreciation
T he s e a re f ive pra ct ic a l c onc e pt s in or d er t o me mo r is e an d t o re min d yo ur se lf wh e n yo u ar e ap p lyin g
J ohre i in e a ch s es s ion a nd a ls o in e ve r yd a y lif e .
T he s e a re th e t it le na mes whic h yo u wi ll ma s t e r in th e t ra in in g s e s s io n .
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We are determined by our intentions
“Gratitude attracts gratitude”
‘Ingratitude attracts ingratitude’
Our life is altered by the way we think
A s m a n y p s y c h o l o g y o r s e -r l f e a l i s a t i o n t e x t b o o k s s a y n o w a d a y s , M o k i c h i O k a d a ing w ta his s e m p h a s i z
c onc ept a lmo s t a ce ntur y a go.
We a r e wh a t we think a nd wha t we wis h t o b e .
I t i s e x a c t l y t h e s a m e t o t h e J o h r e i p r a c t i c e , o f c o u r s e !
Ar e you r e a d y t o t r y one s imple e xe r c ise , wh ic h is th e f ir st st e p f or t he J ohre i pr ac t ic e ?
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P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Tuning in
Feel the ‘Flow of Light’
T h e f i r s t s t e p f o r t -I h N e x e r J c i o s e h . r S h e a l i l w p e r b e a g i c n ? t i c e i s t h i s
Ha ve yo u go t a ny e xpe r ienc e in med it at io n , vis ua lis a t io n , or e ve n s ome s pir it ua l pr ac t ic e like Spir it ua l
H e a l i n g , T h e r a p e u t i c T o u c h , T a i C h i o r ha R ve e i s uk ch i ? kind T h of o s exper e w h ie nce , ple a s e us e yo ur t e c hniq ue if yo u f e e l comf or ta ble a nd wa nt to, bu t ple a se c omb in e t his ‘L I G H T’ c on c ep t wit h it .
I t hink t his FLOWI NG LI GHT is a ver y po we r fu l me t ap ho r, s o be ar t his in min d , ple as e .
Those who have got no expe r ien c e , yo u ma y wa n t t o us e on e vis u a lis a t io n t ec h niq u e I us u all y t e a c h .
I ma gine a b e au t iful pla c e you ha ve b e e n b ef or e , sa y like a b e a c h or p ar k o n a s u n n y b ut n ot a t oo h ot d a y.
You a re s itt in g t her e ha ving t he s u n s h in in g b e h in d yo u . T h e ligh t c o mes fr om t h e Su n a nd yo u c a n fe e l
wa r mt h o n t h e ba c k of your nec k a n d s ho u ld er s . Ho w a b o ut th is ?
Tr y t o FEEL t he light , ple a s e . By t his ‘Fe e l ’ I me a n , an y f ive s e ns e yo u c a n e xp er ie nce , br ight ne s s
( s e e i n g ) , w a r m t h ( t o u c h ) , o r e v e n s o u n d s ( h e a r i n g me ) , ll) s c , e an n t d f( la s vour (t as t e) of the li gh t if yo u
can.
I t is t ot a lly u p t o you whe t her yo u h a ve yo u r e ye s o p e n o r c lo s e d.
Sha ll we b e gin ? P le a se ma ke yo u r se lf c o mf o rt a b le f ir st , an d t hin k T HE LI GHT .
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 71 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
D a i l y J o h r e i T e c h n i q u e H a n d b o o k
for Home P r a c t i c e
D r . A k i r a N A I T O
I m p e r i a l C o l l e g e L o n d o n
Johr ei Ac a dem y ©
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 72 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
I n t r o d u c t i o n
Wel co me t o Jo h r ei p r a ct ice! S o me o f yo u ma y b e n ew to h ea ling o r s pi r itua lity, a n d s o me o f
y o u m a y a l r e a d y b e a n e x p e r i e n c e d h e a l e r er , w ah y, o w e v he op r , e yo e u i fi t nd h in Jo h r ei an
in s p ira t i on a nd s i mp l e mea ns to a cces s ing th e in tima te an d s p ir itua l s pa ce in to w hich yo u ma y
b r ing h ea l in g an d b ea u t y.
Th i s h a nd b oo k i s t o r emind yo u va r iou s tech n iq u es tau gh t o n th e cou r s e, an d pr a ctica l w a ys
of a pp l yi n g Joh r ei ph i l o so ph y. On ce yo u h a ve ma s ter ed th em, n a tu ra lly, yo u w ill no lo ng er
r eq u ir e t h is h an db o o k.
Jo h r ei i s a w o n d er fu l w a y o f ma in ta in in g h ea lth a n d h ap p in es s , b u t a ls o a us efu l s kill fo r
h elp ing p eop l e yo u ca r e ab ou t o u t o f th e g o od n ess o f y o u r h e a r t. ( Rememb er you ca n h ea l
y o u r s e l f b y h e a l i n g o , t if h yo e r u s wan , a t , n yo d u ca n lear n to pr a ctice Jo h r ei pr o fes s io na lly w ith
t h e J o h r e i p r a c t i t i o n e r t r a i n i n g a t t h e J o h r e i A c a d e m y . P l e a s e n o t e s yo t u h a t J o h r e i t e c h n i q
h a v e l e a r n e d i s er n o ap t eu a ti c t tech h n iqu e, a n d you w ill n o t b e a b le to eith er medica lly
d ia gn o s e o r t r ea t p eo p l e.)
We ver y mu ch h o p e t h a t you w ill con tin u e w ith th e Jo hr ei p r a ctice, a nd in w hich ever w a y
yo u ch os e to p r a ct is e it , yo u w ill b e co n trib u ting , little by little fr o m y o u r s u r r o u n d i n g , s to
ma kin g t h is w o r ld b et t er , b eau tifu l an d ha r mo n io us p la ce to live.
M a y t h e l i g h t a n d b e a u t y b e a l w a y s w i t h y o u !
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 73 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
W h a t i s J o h r e i ?
1 O v e r v i e w o f J o h r e i p r i n c i p l e s a n d p r a c t i c e
J o h r e i i s a t h e r a p e u t i c a , r t a n d i n o t h e r w o r d s : a n A r t o f L , i f o v u i n d n e g d i n 1 9 2 0 ’ s
b y a J a p a n e s e a r t i s t , h e al e r a n d s p i r i t u al l e a d e r, M o k i c h i O k a d a .
J o h r e i l i t e r a l l y m e a n s p u r i f i c a t i o n o f s p i r i t . I t s p r i m a r y a i m i s t o f ac i l i t a t e t h e
e l i m i n a t i o n o f t o x i n s f r o m o u r b o d y a n d d i s p e r s i n g o f ‘ c o l m o u o d u s r ’ s p f i r i t i n o r d e r t o
r e v i ta l i s e u s a n d u p l i f t o u r s ou l , th u s r e s to r i n g h a r mo n y a n d we l l -b e i n g .
J o h r e i c a n b e p r a c t i s e d a s a t h e r a p y t h a t t r e a t s i l l n e s s f r o m al l l e v e l s ( m i n d , b o d y
a n d s p i r i t ) o r a s a w o n d e r f u l a n d s i m p l p e r o v w i d a e y u s t w o i t h r e l i e v e s t r e s s
s p i r i t u a l o a w s i t h s i n o u r h e c t i c l i v e s .
W h a t i s u n i q u e a b o u t J o h r e i i s t h a t -t o-l i e a t r n t h e a c s h n i q a u e s f i o r m p l i f i e d , e a s
y o u to p r a c ti s e a t h o me i n o r d e r to ma i n ta i n h e al th a n d we l l -b e i n g . T h e s e h a n d o u t s
o u t l i n e t h e s e t e c h n i q u e s f o r y o u t o l e ar n a n d p r a c t i s e .
J o h r e i al s o e x t e n d s b e y o n d i ts h e al i n g p r a c t i c e . I t i s a n A r t o f L i v i n g t h a t c o v e r s
t h e f o l l o w i n g t h r e e as p e c t s :-
1 . H E A L I N (Ar G t of lif e) - T r u s t t h e a b i l i t y o f h u m a n b e i n g
2 . B E A U T Y - A p p r e c i a t i o n o f B e a u t y , e n l j i o f y e b e a u t y i n
3 . N A T U R E - L i v i n g i n h a r m o n y w i t h n a t u r e , N a t u r a l f a r m i n g , d i e t a n d n u t r i t i o
J o h r e i a c t i v i t y o v e r t h e d e c a d e s g av e r i s e t o i t s o w n u n i q u e f l o w e r a r r a n g e m e n t
s ch o ol , SA N G ET S U , i ts o wn c h e mi c al -f r e e f a r m i n g t e c h n i q u e , N A T U R E F A R M I N G , i t s o w n
t e a c e re m o n y , B O N T E M A E , a n d v a r i o u s a r t m u s e u m s , g a r d e n s o f e x q u i s i t e b e a u t y a n d
s a c r e d g r o u n d s . A s a p r a c t i t i o n e r o f J o h r e i y o u w i l l h a v e a c c e s s t o a l l o f t h e s e .
P r i n c i p l e s o f J o h r e i
T o x i n s
T h es e a r e e n ti ti e s ( ch e mi c al s , i n ap p r op r i a te me d i c i n e, p ol l u ti o n , e tc . ) t h a t a r e n o t
i n t e n d e d f o r o u r n a t u r a l c o n s u m p t i o n . P r o b l e m s b e g i n t o o c c u r w h e n t h e y e x c e e d
b e y o n d o u r n a t u r a l c a p a c i t y a n d b e g i n t o a c c u m u l a t e i n o u r b o d y as t o x i n s . In t h i s
s e n s e , f o o d i n e x c e s s c a n b e c o m e t o x i c .
C l o u d s
T h i n k o f t h e s e a s t h e g l o o m t h a l t o o m s o v e r u s i n o u r s p i r i t w h e n w e a r e ‘ u n d e r t h e
w e a t h e r ’ . T h e y m a n i f e s t w h e n w e a r e u n d e r s t r e s s , e m o t i o n a l l y c h al l e n g e d o r
b e c o m e t o x i n i n f e s t e d .
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 74 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
T h e P r o c e s s o f P u r i f i c a t i o n
T h e T o x i n s a n d C l o u d s a r e c o n s t a n t l y u n d e r g o i n g a n t i a n t g . u r a l p r o c e s s
T h i s i s c al l e d t h e p r o c e s s o f p u ri f i c a t i o n . T h i s i s a n a t u r a l l y o c c u r r i n g p r o c e s s o f
d e t o x i f i c a t i o n a n d s p i r i t u al u p l if t . J o h re i e n c o u r a g e s t h i s p r o c e s s i n a d i r e c t e d w a y
a n d al l e v i a t e s d i s c o mf o r t .
S p i r i t p r e c e d e p h y s i c a l
W e a r e w h a t w e t h i n k el . a O n u d r me f e n ta l , e mo ti o n al a n d s p i r i tu al wel l -b e i n g i s o f
u t m o s t i m p o r t a n c e . T h e p r o b l e m b e g i n s i f w e i g n o r e t h i s s i m p l e t r u t h a n d l e t o u r
mi n d a n d s p i r i t g o o u t of s y n ch wi th o u r b od y . ( S e e al s o n e x t p a g e )
I Z U N O M E
I Z U N O M E i s a s t a t e o f b a l a n c e, h a r m o n y d a n p p r o p r i a t e n . e I s t s i s t h e m i d d l e w a y
w h i c g h i v e s u s t h e a b i l i t y t o l o o k a t b o t h s i d e s o f a s i t u a t i o n s o t h a t y o u c a n
m a i n t a i n t h e b al an c e . S o m e t i m e s w e n e e d t o t r u s t a n d l e t g o , o t h e r t i m e s w e n e e d t o
t a k e o u r d e s t i n y i n t o o u r o w n h a n d s a n d w h a e c n t . o a c K t n o r w i h n e g n t o l e t g o
i s n o t e a s y u n l e s s y o u c a n s e n s e t h a t . Y o u w i l l b e ab l e t o s e n s e i t b y b e i n g i n t h e
s t a t e o f Iz u n o m e w h i c h p r a c t i c e s o f J o h r e i l e a d y o u t o .
T h e P r o c e s s o f P u r i f i c a t i o n
T h i s i s a n a t u r a l l y o c c u r r i n g p r o c e s s t s h t o a x t i n e s l a i n m d i c l n o a u t d e s f r o m t h e
b o d y a n d t h e s p i r i . t
I t o c c u r s i n t w o s t a g e s :
( 1 ) A c c u m u l a t i o n
T o x i n s a c c u m u l a t e a r o u n d d i f f e r e n t a r e a s o f t h e b o d y , w h i c h a r e u s e d f r e q u e n t l y .
T h i s m e a n s t h a t t h e a r e a s o f t o x i n a c c u m u l a t i o n v a r y f r o m p e r s a o s n t o p e r s o n . A r e
o f s t i f f n e s s , ‘ k n o t s ’ i n t h e m u s c l e s , s w e l l i n g , a n d t h e a r e a s o f p a i n a r e s a i d t o b e d u e
t o t h e t o x i n a c c u m u l a t i o n . T o x i n s a l s o a c c u m u l a t e d e e p w i t h i n o u r b o d y a n d a f f e c t
o u r i n t e r n a l o r g a n s .
( 2 ) E l i m i n a t i o n
W h e n w e a r e w e l l , o u r b o d y n a t u t r e s a l t o l x i y n s . e T l h i s m h i a n p a p e n s w h e n w e g o
t o t h e t o i l e t , s n e e z e , c o u g h , a n d s w e a t o r s h e d s k i n s . W h e n t h e t o x i n a c c u m u l a t i o n
i s s e v e r e , e l i m i n a t i o n p r o c e s s m a y a l s o b e p r o n o u n c e d a n d a c c o m p a n i e d w i t h
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 75 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
d i s c o m f o r t . F o r -l e i k x e a m s y p m l p t e o , m s f o r d l i u a r r h o e a a r e m s y p t o m s o c c u r r i n g a s
t h e r e s u l t o f t o x i n e l i m i n a t i o n . W e t e n d t o s e e t h i s e l i m i n a t i o n p r o c e s s a s a n
i n c i d e n t o f m i n o r i l l n e s s , h o w e v e r , t h e y a r e o u r b o d y ’ s w a y o f m a i n t a i n i n g o u r
h e a l . t h
H o w J o h r e i W o r k s
J o h r e i w o r k s b y d i s p e r s i n g t h e c l o u d s i n t h e s p i r i t . T h i s e l i m i n a t e s t h e n e g a t i v i t i e s
w i t h i n u s , t h u s g i v i n g u s g r e a t e r v i t a l i t y a n d e n c o u r a g i n g o u r b o d y ’ s n a t u r a l a b i l i t y
t o e l i m i n a t e t o x i n s .
F u r t h e r m o r e , i t i s t h o u g h t t h a t J o h r e i i t s e l f h e l p s t o d i s s o l v e a w a y t h e
a c c u m u l a t e d t o x i n s o r ‘ b u r n a w a y ’ t h o e x i t n s t h e m s e l v e s , t h u s h e l p i n g t o s u p p o r t
t h e b o d y ’ s i m m u n e f u n c t i o n a n d t h e f u n c t i o n o f o t h e r o r g a n s e s p e c i a l l y k i d n e y s
w h i c h f i l t e r s o u t t o x i n s f r o m o u r b l o o d .
J o h r e i
T o x i n s B o d y S p i r i t C l o u d s
U s
I n t e r a c t i o n b e t w e e n B o d y a n d S p i r i t
I n J o h r e i i t i s b e l i e v e d t h a t t h e s p i r i t a n d b o d y i n t e r a c t i n s u c h w a y t h a t
a c c u m u l a t e d t o x i n s c a s t ‘ c l o u d s ’ i n o u r s p i r i t , a n d t h e ‘ c l o u d s ’ t h e m s e l v e s c a u s e
i m p u r i t i e s i n o u r b l o o d t h a t l e a d s c e t i o l l t n . o e s x s i n b u i l d u p a n d h e
S p ir i t p r e c e d e s P h ys i c a l
O n t h e o t h e r h a n d , w h e n t h e ‘ c l o u d s ’ i n t h e s p i r i t a r e d i s p e r s e d t h i s e n c o u r a g e s
t o x i n s i n t h e b o d y t o b e e l i m i n a t e d . J u s t a s o u r w i l l l e a d s t o t h e a c t i o n i n o u r b o d y ,
i t i s b e l i e v e d t h a t t h e s t a t e o f o u r s p i r i t ( m d i a n d e m o t i o n ) i n f l u e n c e s o u r p h y s i c a l
w e l l -b e i n g . T h i s p r i n c i p l e i s c a l l e d t h e S p i r i t p r e c ed es P h y s i c al . B a s e d o n t h i s
p r i n c i p l e , J o h r e i p r a c t i t i o n e r w o r k s b y c h a n n e l l i n g t h e U n i v e r s a l E n e r g y ( r e f e r r e d t o
a s “ t h e L i g h t ” ) w i t h t h e i n t e n t i o n o f d i s p e r s i h n e g ‘ t c l o u d s ’ i n t h e s p i r i t a n d
e l i m i n a t i n g t o x i n s .
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P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
2 . T h e F i n g e r R u l e f o r p r e p a r i n g y o u r s e l f f o r t h e J o h r e i e x p e r i e n c e
You can use the following rules to help you not only with Johrei practice but to prepare yourself
consciously for anything, from flower arranging, art, music, sports to the life in general.
V i s u a l i s e t h e s e r u l e s a s y o u c o u n t t h e m o u t w i t h t h e f i n g e r s o f y o u r h a n d ,
s t a r t i n g : w i t h
T h u m b ( T ) -T u n i n g i n
F i r s t , t u n e i n t o . t h e s o u r c e
Tune into the source of your energy, with love, inspiration and your very being. The source
exists at the centre of the Universe and it is up to you whether you think of it as your higher self,
God, the Spirit of the Sun, Nature or the Cosmic Consciousness.
T h i s p r o c e s s i s l i k e a T V o r a r a d i o ; i f y o u d o n o t t u n e i n , y o u c a n n o t o b t a i n a
b e a u t i f u l p i c t u r e o r c l e a r s o u n d s a l t h o u g h y o u h a v e a n a n t e n n a t o r e c e i v e i t . Y o u a l s o
e m p o w e r t h e a n t e n n a b y p r a c t i s i n g J o h r e i .
I n d e x f i n g e r ( I ) –I n s p i r a t i o n a n d I n t e n t i o n
B e I n s p i r e d a n d h o l d h e a l i n g i n t e n t i o n
Let the source of Universal Love inspire you by your loving intention for the healing of yourself
and others.
M i d d l e f i n g e r ( M ) (w i t h I n d e x f i n g e ( I r ) )
–M e n t a l i t y ; t h e M i d d l e w a y ( I Z U N O M E )
S t i l l t ba l h a n e c e a m n d i h n a r d mo n y & wi t h t i mi n g : Tr y h a r d f i r s t t h e n t r u s t!
If your intentions are always for the good of mankind, there is nothing to be afraid of. Allow
your stress to melt away and clear your mind. Everything that happens to you is enable you t o
help you become happier, healthier and stronger. A raw diamond has to be polished to shine.
You will find your soul is purified & enlightened by these processes. Keep a smile on your face
always.
R i n g f i n g e r ( R )
–R e l a x s o t h a t y o u c a n E N J O Y y o u r s e l f
R e l a x y o u r b o d y a n d t a k s e o t i h a t y o e u a s c y a n e n j o y y o u r s e l f !
Rocks can be crushed if the force is strong enough, but free flowing water is adaptable to its
surroundings. Always keep the body relaxed and flowing and you will never be crushed. It is all
about learning to trust and let go. Relaxing your body will also improve your Johrei practice.
L i t t l e f i n g e r ( L ) –L e t t h e L i g h t f l o w !
i t h L w o v e & M A K O T O ( i n t e g r i , s t i y n c e r i t y , l o v e )
T r u s t in t h e u n i v e r s a l f l o w & t r u s t y o u r s e l f. L o v e f o r o t h e r s & M . A K O T O t o y o u
Let go and let the light flow. Once you are relaxed, open and tuned in, you can flow with the
light.
Opening your palm to receive gratitude!
G r a t i t u d e a t t r a c t s g r a t i t u d e !
E v e r y t h i n g t h a t h a p p e n s l e a d s t o y o u r e l e v a t i o n . I f y o u a r e i n t h e s t a t e o f g r a t i t u d e
a n d a p p r e c i a t i o n , t h i n g s y o u d e s i r e , w i l l a l w a y s c o a m y .
e y o u r w
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 77 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
3 . P o i n t s t o n o t e b e f o r e g i v i n g J o h r e i
1. Take note of how you are feeling before you give Johrei.
2. Choose comfortable surrounding where you will not be interrupted or disturbed during
Johrei. Try choosing an area where there is harmony or beauty, possible nears a flower
arrangement.
3. Choose two comfortable seats, if possible stools with swivelling seats. However, seating
must be chosen to suit the person receiving Johrei. If the person cannot remain seated
for more than 10-20 minutes, adapt your Johrei accordingly. It is important that person
who is receiving Johrei is informed that it will take this long before hand.
4. A guide to the positioning of your self and your partner is as follows:-
T h e L i g h t i s s a i d t o f l o w f r o m t h e n o r t h yo e a us r se t lf ws o it h i yo d ue r a back l l y t o p to he s i t i o n
no r t heast .
It is more important that you do not have your back to the door. Position your
self so that you are in the opposite part of the room from the door.
5. Take care to note if the person about to receive Johrei is already undergoing some sort of
Purification Process or the person is known to undergo pronounced Purification when
receiving Johrei or other forms of healing. Remember that Johrei is about encouraging
the Process of Purification. Although, Johrei will generally alleviate any discomfort, use
your best judgment to decide whether it is best to proceed with Johrei or allow the
process to take its own course and support it with Johrei at a later stage. If you decide to
give Johrei in such a situation, it may be more advisable to adapt or shorten your Johrei
accordingly, rather than doing the whole sequence. If in any doubt seek professional help
before proceeding.
6. If the person to whom you are intending to give Johrei is suffering from acute pain,
severe discomfort or very high fever, especially if the person is a child or pregnant please
seek professional help without delay.
7. Be prepared for emerging emotions. Even though the person you are giving Johrei may be
suffering from physical discomfort or no obvious discomfort at all, you may find that
there are underlying emotions needing to be expressed, Johrei often allows these
emotions to emerge. It can be the case that such emotions are dispersed by Johrei
however, you should be ready to talk. Talking can sometimes be hard amongst friends or
family. Ask yourself if you are prepared to handle it. If the person wishes to talk or cry,
let the person lead the situation. Humility and sincerity is the key. Be there, listen with
an open heart but do not advise or judge. I f in doubt seek professional help.
8. Heal your self by healing others. Johrei can benefit you when you give it to others. This is
because you receive the Light before you channel it, and through the healing in your
partner you are also healed. The feeling of appreciation and gratitude from your partner
will also provide you with an up-lift.
9. Make sure you are comfortable when you give Johrei. If you cannot remain in a seated
position for a long time, arrange your seating or length of Johrei accordingly. If you
cannot raise your arm for a long time support it with the other arm or rest it on an
armrest or a table.
10. You must feel comfortable to give Johrei. If you are too unwell, just receive Johrei from
whoever is offering to give it to you and then rest, don’t feel you are obliged to give Johrei
each time.
11. JUST ENJOY the feeling of intimacy, happiness and joy of returning the love and care
you have received from others. Empower your self to help others and in so doing, help
yourself.
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 78 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
4 . a s i B c J r e o i h s e q u e n c e f o r f a m i l y p r a c t i c e
1. Sit facing each other.
2. Take a moment to relax and prepare yourself (with the 5 finger guide)
3. Greet and acknowledge each other.
4. Tune in by visualising the source of the Light. Channeling the Light is like ‘playing the
music of the universe’. Appreciate the occasion and if you can, fill your self with gratitude
and joy. Sense of gratitude will allow yourself to be healed in the process of giving Johrei
and you will feel less tired during Johrei. The effect may be further enhanced if you can
feel and visualise the happiness and the positive outcome for the person you are giving
Johrei.
5. Gently raise your hand, relax your arm, cup your palm and begin by channelling to the
forehead (2 minutes)
6. Gently lower your hand to the area near the heart and give Johrei there. (2 minutes)
7. Ask your partner to turn around. Take a moment to tune in again.
Stand up, and steady your partner. Then gently proceed to channel to the crown of your
partner’s head. (2 minutes)
8. Channel to the both sides of the neck with your hand (left side first and then right).
Remember to cup them.
(2 minutes (1 minute each))
9. Cup your hand and place them on the shoulders (left side first and then right again). (2
minutes (1 minute each))
10. Then proceed by cupping your hands and giving Johrei to the centre of your partner’s
back so as to channel to the liver, pancreas and stomach. (2 minutes)
11. Place your hands on either sides of your partner’s lower back and give Johrei. This
stimulates the kidneys. The Kidneys are important organs for purifying the blood.
General fatigue can also be supported by energising the kidneys.
(4 minutes (2 minutes each))
12. Finish off by raising one hand as if to give a shower of Light. (1-2 m i n u ) t e
13. Signal your partner that you have finished with a gentle tap on the shoulders and ask
your partner to face you once more. Thank each other. (Remember you have benefited
by giving Johrei too).
14. If your partner also practised Johrei then do not hesitate in proceeding to receive Johrei
because Johrei is something to be shared!
P o i n t s t o n o t e a f t e r J o h r e i :
I t d o e s n o t m a t t e r w h e t h e r y o u r p a r t n e r o r y o u r s e l f d i d n o t f e e l a n y t h i n g d u r i n g
J o h r e i , o r e v e n t h a t y o u r p a r t n e r d i d n o t i m m e d i a t e l y f e e l a n y e f f e c t o f i t . T h e e f f e c t o f
J o h r e i c a n j u s t a s w e l l t b l e o r d u e n l n a o y t i e c e d a , b l e . s u b
R e f l e c t m o r e h o w i t w a s l i k e f o r y o u , h o w y o u f e l t a f t e r w a r d s . A n d t h i n k o f h o w y o u
m i g h t d o i t d i f f e r e n t l y fo i r n e v e f n u t b u e t r t e r r e s u l t s .
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 79 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
5 . a s i B c t e c h n i q u e o f S e l f J o h r e i
1. Sit on a comfortable chair. It will be more effective if you sit upright.
2. Close your eyes and take a moment to relax and tune in with the Five-finger guide.
3. Tune into the source of the Light by visualising the spirit of the Sun over and above you
shining down a beautiful Light.
4. When you can feel the flow of the Light reaching down to you, slowly raise one hand and
channel to your forehead. Your arm should be relaxed, as it would be when channelling
Johrei in pairs. (2 minutes)
5. Slowly move your hand down to your chest area passing through the throat. Channel Johrei
to your heart. Enjoy the warmth & any alleviation of tension. (2 minutes)
6. Lower your hand further to your stomach area. This area is related to anger and irritation.
Channel Johrei here in order to calm you and make you feel more positive. (2minutes)
7. With one hand at a time, channel Johrei to your groin (left side first then right). (1 minutes
each side)
8. Cover your tailbone with one hand and channel Johrei to the sacrum. This will help the
womb in women, and also your intestines and digestive system. If you have a particularly
problematic digestive system, you may also combine this with channelling Johrei to the
lower abdomen from the front.
9. If you are suffering from period pains, irregular period cycles, menopause or fertility
problems you can follow this up with channelling Johrei with two hands placed on either
side of your abdomen followed by one hand three finger width below your belly button. (in
this occation1-2 minutes each position)
10. Then from the front, channel to the kidneys (left side first) or cup you hand and place it on
your lower back (left first then right). (2 minutes each) Your lower back is related to your
kidneys. Kidneys are important organs for eliminating toxins and filtering blood. Stiffness
in your lower back indicates that kidneys are weakened and that excessive toxins have
accumulated there. If the kidneys are over worked, it will take extra energy to filter your
blood hence you will feel physically drained. Use your hands to press away the stiffness
and then channel Johrei if you feel comfortable.
11. Cup your hands and gently place them on your shoulders. You may prefer to do this one
shoulder at a time. Your shoulder is a barometer for your general health. Make sure they
are always free of stiffness and tension. Your left shoulder is closely associated to your
heart. Spend more time channelling to your left shoulder if you have a heart condition. (1-2
minutes each side)
12. With one hand at a time, channel Johrei to both sides of your neck (left side first the right).
(1-2 minutes each side) This will help the toxins to move down from your head and support
the alleviation of headache.
13. Finally, channel to the forehead like a shower of Johrei! (1 minute)
14. Please note that Johrei, just like every other healing, is effective both when you give it and
receive it. So treat Self-Johrei as a daily self-maintenance practice for improving your
Johrei. Always try to look out for anyone who will receive Johrei.
R e m e m b e r , w i t h J o h r e i ,
Y O U H E A L Y O U R S E L F B Y H E A L I N G O T H E R S
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 80 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
6. V i s u a l i s a t i o h n r e i f p o r ac t J i c e
T h e f o u n d e r of J o h r e i , M o k i c h i O k a d a s a i d t h a t w e a r e w h a t w e t h i n k a n d o u r
i n t e n t i o n a l t e r s o u r l i f e , a n d a l s o t h a t w h i a t s e c v r e r a t e d i n t h e s p i r i t u a l d -i
m e n s i o n p r e
e m p t s t h e c h a n g e s t a k i n g p l a c e i n t h e p h y s i e c s a p l h y s i d c i al m ) . e n s i o n ( S p i r i
T h e s e c o n c e p t s p a r al l e l t h e w o r k c a r r i e d o u t b y t h e S i m o n t o n s i n t h e U S A . B a s e d o n t h i s ,
i t i s o b v i o u s t h a t v i s u a l i z a p t l a i y s o a n n i m p o r t a n t r o l e i n w h a t e v e r w e d o . V i s u al i s a t i o n
i s s o p o w e r f u l s u c h t h a t i t c a n e v e n d e t e r m i n e t h e d i r e c t i o n t h o f e f l o w o f L i g h t o r t h e
o u tc o me of J o h r ei .
D i r e c t i n g t h e f l o w
I n J o h r e i , y o u t u n e i n b y v i s u a l i z i t h n e g s o u r c e o f t h e L i g h t a n d a s k i n g i t t o h e l p y o u
b y c h a n n e ll i n t g h e L i g h t t o t h e r e c e i v e r . T h e c h a n n e l l e r v i s u a l i s z t e h e f l o w o f t h e L i g h t
f r o m t h e s o u c r e , t h r o u g h h i m / h e r t o t h e r e c e i v e r .
T h e c h a n n e l l e r c a n i n t e n s i f y t h e e f f e c t o f t h e L i g h t b y v i s u a l i z i t n b g e i n g f o c u s e d b y
t h e c u p p e d h a n d a s i f i t i s a m a g n i f y i n g l e n s a n d b e a m e d t h r o u g h t h e b o d y o f t h e
r e c e i v e r t o t h e o t h e r s i d e .
T h o s e w h o a r e s e n s i e t t i o v p e o p ’s l e n e r g y a n d i n t e r n a l e m o t i o n a l s t a t e s , v i s u a l i z e
y o u r s e l f a s a r i v e r r a t h e r t h a n a b o w l o f w a t e r . W h e n p e o p l e w a s h t h e i r d i r t y l i n e n i n
y o u r b o w l o f w a t e r , i t l e a v e s t h e w a t e r d i r t y . H o w e v e r , i f y o u a r e a f r e e f l o w i n g r i v e r ,
t h e d i r t i s w d a s w h e a y a n d t h e w a t e r i s a l w a y s p u r e a n d c l e a n .
V i s u a l i s i n g t h e o u t c o m e
I t i s h e l p f u l t o k n o w b e f o r e h a n d t h e h o p e a n d t h e w i s h e s o f t h e r e c e i v e r . A s a
c h a n n e l l e r , y o u c a n v i s u a l i t z h e e w i s h e s o f t h e r e c e i v e r w h i l e y o u g i v e J o h r e i . I t m a y
b e h e l p f u l t o v i s a l u i z a e f i l m s c r e e n o n t o w h i c h t h e f i l m s o f t h e f u t u r e e v e n t s a s w i s h e d
b y t h e r e c e i v e r a r e s c r e e n e d .
T h e r e c e i v e r c a n b e e n c o u r a g e d t o v i s u a l i z t h e e f u t u r e o u t c o m e s i n t h e s a m e w a y i f
y o u w a n t , b u t d o n o t c o m p e l h i m / h e r t o d o s o p l e a s e .
V i s u a l i s a t i t o h n e r b e y c e i v e r
I t i s o f t e n f o u n d t h a t t h e r e c e i v e r i s u n s u r e h o w t o s i t d u r i n g J o h r e i a n d a l s o a s k s
t h e c h a n n e l l e r w h e t h e r i t i s n e c e s s a r y f o r t h e m t o m a k e h i s / h e r m i n d b l a n k . I t i s
u n d e s i r a b l e f o r t h e r e c e i v e r a s w e l l a s t h e c h a n n e l l e r t o b e s t r u g g l i n g t o v i s u a l i z o e r t o
b l a n k t h e i r m i n d s .
I t i s f a r m o r e i m p o r t a n t t o r e m a i n i n a n a t u r a l s t a t e . V i s u a l i s e o n l y i f i t b e c o m e s
n a t u r a l t o y o u a n d t o t h e r e c e i v e r . A u s e f u l w a y o f q u i e t e n i n g t h e m i n d J o h r e i w a y i s
t o a l l o w a n y t h o u g h t s t o a r i s e i n t g h i n e t h e a m d t o a n b d e c l i o u m d a s w h i c h a r e
d i s p e r s e d b y t h e L i g h t o f J o h r e i . M o r e J o h r e i y o u p r a c t i c e , y o u w i l l f i n d t h a t t h e m i n d
q u i e t e n s n a t u r a l l y w i t h o u t m a k i n g a c o n s c i o u s e f f o r t .
V i s u a l i s i n g t h e p a s t a n d t h e f u t u r e
I n J o h r e i , i t i s s a i d t h a h t y s i s c p a i l . r B y i u t p l i p f ti r n e g c t e h d e e p s a s t p a n d t h e f u tu r e
w i t h J o h r e i , y o u c a n u p l i f t t h e p r e s e n t.
W h e n y o u a r e g i v i n g J o h r e i f r o m t h e f r o n t o f t h e r e c e i v e r e s p e c i a l l y a t f o r e h e a d ,
v i s u a l i a z e p a t h w a y f r o m t h e p a s t b e h i n d t h e r e c e i v e r , a l o n g w h i c h h e / s h e h a d t o
t r a ve l . I t i s h i s / h e r p a s s a g e f r o m t h e p a s t . V i s u a l i s e t o c l e a r t h e h u r d l e s i n i t w i t h
y o u r J o h r e i . W h e n t h e r e c e i v e r t u r n s a n d y o u a r e g i v i n g J o h r e i f r o m b e h i n d , v i s u a l i z e
a p a s s a g e i n f r o n t o f t h e r e c e i v e r . I t i s h i s / h e r p a t h i n t o t h e f u t u r e . V i s u a l i s e t h a t y o u
e n l i g h , t e n e n r g i s e a n d h e a l t h e p a t h f o r y o u r r e c e i v e r w i t h J o h r e i .
I t i s u p t o y o u a s a J o h r e i oo s e p w r h a i c t h i v i t s i u o a n l e i r z a t o t o u i s e o c n o h r n o t t o u s e
v i s u a l i z a t a i l l o . n
W i t h p r a c t i c e , y o u w i l l f i n d t h e s e c o m e t o y o u n a t u r a l l
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 81 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
7. S e n s a ti o n s f e l t d u r i n g J o h r e i
T he f ollowin g is a guide t o und er st a nd in g t he me a nin g of s ome of t he s e ns a t io ns fe lt by th e c han ne lle r
or t he re c e ive r dur ing the J ohr e i pr oc e ss . I t mu s t be not e d th a t t he se a r e not off ic ia l t ea c hings a s t a ught by M o k i c h i O k a d a e , f ound t h er of J ohr e i. Use this inf or mat io n as e xa mp le s .
H e a t
I n t he Jo hr e i pr inc ip le o f t he pu r ific at io n pr o cess, it is u nder st oo d t hat when t he accu mu lat ed and so lid if ied t o xins beg in t o ‘me lt ’, t he pro cess is ac co mp a nied by a lo ca lis ed t emper at ur e r is e. T he char act er ist ic o f t his i s t hat yo u w il l
fee l t he heat up o n co nt act as well as awa y fr o m t he bo dy. I f yo u fee l t he heat fr o m t he r ece iver yet yo u fe e l
COLDNE S S in yo ur ha nd whe n c ha nne l l ing Jo hr e i, it usua l l y ind icat es t hat t he pur ific at io n pr o cess of me lt in g t o xin s
is t ak ing p la ce in t he ar ea and it is dr aw ing in t he L ig ht fr o m yo ur ha nd t o su ppo rt it ( see co ld nes s be lo w) .
T he he at fe lt by t he r ece iver is t he L ig ht whic h is be ing c ha nne l led. I t is usu a ll y fe lt be lo w t he su r fac e . Ho w deep
t h e r e c e i v e r ee f ls t he heat dep end s o n ho w far awa y t he cha nne ller 's ha nd is. T he fur t her awa y t he ha nd fr o m t he
r ece iver , t he DE EP E R t he heat o f r ece iver . Tr y no t t o co nfuse t he c ha nne l ler 's bo d y heat w it h t he heat sen sat io n o f
t h e L i g h t ( i t h a s b e e n k n o w n w it t h co a t ld ha a nd p s e r ca s n o st il l pr o du ce t he heat sensat io n w it hin t he r ece iver ) .
I f t he c ha nne l ler fee ls t he heat co ming fr o m t he r ece iver w it h no r esult ing t o t emp er at ur e r ise, it usu a ll y in d ic at es t hat
t he ar ea r eq uir es no fu r t her cha nne l l ing.
C o l d n e s s
T h e mo st well r eco gn ised se nsat io n ot her t han t he heat is t he se nsat io n o f co ld ne ss. T he ar eas w it h co ld se ns at io n
ar e t he ar eas in need o f hea l in g . I f t he cha nne ller fee ls t he co ld ne ss in his/ her ha nd whe n g iv in g Jo hr e i, it ind ic at es
t h a t t h e a r e a i ts he d Lr ig a ht w i in n ag nd hea lin g is t ak ing p lace. Not ice if t he ar ea beco me s war mer as Jo hr e i is g ive n.
I f t he r ece iv er fee ls t he co ld ne ss in t he ar ea be ing g ive n Jo hr e i, find o ut if t he c ha nne l ler is fee l in g t he heat in his/ her
ha nd . I f so , it usu a ll y ind ic at es t hat t he L ig ht is flo w ing in t he wr o ng d ir ect io n. S t o p , t une in ag a in a nd cha nne l by visu a lis in g t he L ig ht be in g fo cu sed by t he cha nne ll er 's ha nd a nd flo w in g fr o m t he c ha nne l ler t o t he r ece iver .
I t w i l l h e l p t o v i s u a l i s e t h a t t h e b r oe ug a m h t he o f r ece L i iver g h 't s bo p di y e tr o c t he i n og t her t h s ide. Ot her co ld
se nsat io ns ma y e xist su ch as t he se ns at io n o f co ld ness at t he co r e o f t he r ece iver 's bo d y, wh ic h me lt s awa y l ik e
me lt in g ic e. T his in t he past has in d icat ed a pro fo und hea l ing.
T i n g l i n g , m a g n e t u l i s io c n r a e n d p th e s e n s a t i o n o f m o v e m e n t
T ing l in g se nsat io n in t he ha nd o f t he cha nne l ler ca n o ccur t o var ying deg r ees. S uch t ing lin g se nsat io n ind ic at es t hat
a he a l in g p r o c e s s in w h ic h t he L ig ht is d r a w n t hr o u g h t he c ha n n e lle r t o t he a r e a w he r e t he p u r if ic a ot n i pr o cess is
t aking p lace. Fo r Jo hr e i, an y t ing l ing se nsat io n ind icat es t hat t o xins ar e o n t he mo ve. S o t he t ing l in g sen sat io n in t he
cha nn e ller 's bo d y ma y mea n t hat t he pur ificat io n p r o cess is t aking p lace t her e.
T he se ns at io n o f mag net ic r ep u ls io n mea n t hat t he po lar it y o f t he cha nne l ler 's ha nd a nd t he ar ea r ece iv in g Jo hr e i
ma y be t he sa me, he nce t he r ep u ls io n. Jo hr e i is a bo ut cha nne l l ing t he L ig ht fr o m t he Un iv er se a nd no t t he mag net ic
ener g y o f t he ch a nne l ler 's bo d y. T her e fo r e, if t he c ha nne l ler fe e ls t he se nsat io n o f mag net ic r ep u ls io n in Jo hr e i, t hen
st o p and t une in ag a in.
P a i n
Whe n t he e li m in at io n t ak es p lace a nd t he t o xins be g in t o me lt and mo ve awa y fr o m t he ar ea be ing g iv en Jo hr e i, t he
r e c e ive r ma y f e e l t he s e ns a t io n o f t o xin s f lo w in g a w a y. I f he t r ece iver fee ls su c h se nsat io n, it can o nly be a po sit ive
ind icat io n. I f su c h se nsat io n is unco mfo r t able o r pa infu l, fur t her Jo hr e i ma y be g ive n t o make t he pr ocess mo r e
co mfo r t ab le.
P a i n i n d i c a t e s t h a t t h e t o x i n s i n t h a t a r e a a r e m e l y. t i Du n g r in a g n d Jo hr m o e i, v i it n ma g a y w be a fo un d t hat t he
ar ea o f pa in, kno t s and st iffn e ss pr o gr ess ive l y mo ves do wn t o war ds t he kid ne ys. I f it do es, t he pu r if ic at io n pr o cess is
p r o c e e d i n g a s i t s h o u l d . E n c o u r a g e t h e r e c e i v e r b y l e t t i n g t h . e Im f t he k n ar o ea w ot f ph a in t is t no h t i s i s a g o o d s i g
mo vin g , is beco min g int en se o r is mo ving in t he w r o ng dir ect io n ( upwar ds awa y fr o m t he k id ne ys) , use st ro king t o
enco ur ag e t he t o xin flo w do wnwar ds.
C o l d d r a f t
I f t h e c h a n n e l l e r o r t h e ing ho r izo e c nt ae ll y i acr v oe ss r t he ar f ea e r ece e ivi l ng s Jo hr a e i, it d is r a f t o f c
sa id t o ind ic at e t hat t he ar ea r eq uir es no fur t her Johr e i at t hat t ime.
The s e a r e g ui d el ine s only and tr ue u n d er st a nd i n g c a n on ly c o me fr o m y ou r o wn e x p e ri e nce g a in e d
t hr ough r e p ea te d pr act ic e .
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P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
8. T a k i n g C a r e o f S y m p t o m s o f P u r i f i c a t i o
It is likely that through the Johrei practice, toxins within your system start to be eliminated. This
will lead to better health and improvement of your current condition. The symptoms of elimination
(process of purification) vary from cold like symptoms to diarrhoea. The severity depends upon
various factors. The following may be a useful to note.
1. History of illness, (how long have you suffered from your current condition, how severe is it,
what other illness have you had in the past)?
2. Symptomatic medication you have been using (medicine is useful in suppressing the
discomfort, however, later your body will need to eliminate it if it is not appropriate.)
3. Your general well being. As your health improves, you may find that your body will start to
eliminate the toxins that were accumulated in the past.
The above will take place irrespective of whether you give or receive Johrei or not. With Johrei
you will find that the elimination process is quicker, with less discomfort. You will also find that
more toxins are eliminated; the elimination process will be less prolonged and less intense.
H o w t o m a n a g e t h e ‘ p u r i f i c a t i o n ’ s y m p t o m s
F e v e r :
We know that our immune system can be most activated at the body temperature of 38 to 40
degrees Celsius. If you are feverish, just take a rest, relax and sleep well in peace (ideally with
supportive Johrei to the kidneys).
When fever causes you to be unable to drink or sleep, an antipyretic such as aspirin helps to
prevent dehydration or exhaustion.
D i a r r h o e a :
Warm water is the best thing to take at this time as well as keeping your stomach warm.
Diarrhoea is usually a self-limiting symptom, it should last at most about 1-2 days with or
without a severe period of less than 12 hours. What a doctor worries about is dehydration and
exhaustion. Consequently, if you cannot drink water for 12 hours, you should go and see a
doctor to have fluid supplied intravenously.
S w e a t i n g o r c h i l l i n g
Once again, warm water is the best thing to take at these times. Keep yourself comfortable by
changing your clothes, wearing warm clothes etc.
C o u g h i n g
Coughing is the way to throw sputum out. In Johrei philosophy, toxins can gather in sputum
or in other discharges as well as into urine. When it hurts, give Johrei from the middle of back
to alleviate it.
P a i n
If you or your partner gets acute discomfort, contact a doctor without delay.
In Johrei philosophy, it is thought that accumulating or melting toxins cause some discomfort.
This can be a sign that the elimination process is taking place. Johrei, however, is a wonderful
and simple way to alleviate discomfort and help your body to detoxificate.
9 . h T e k e y a r e a s
1 . F o r e h e a d
2 . C r o w n
3 . T e m p l e s
4 . B a c k o f t h e n e c k a n d t h e b a s e o f s k u l l ( m e d u l l a o b l o n g a t a )
5 . B o t h s i d e s o f t h e n e c k f r o m t h e d i p b e h i n d t h e e a r s d o w n t o t h e c o l l a r b o n e o r
s h i r t c o l l ar ( l y m p h a t i c n o d e s )
6 . K i d n e y s : T h e m o t i o n i s a l w a y s d o w n f r o m t h e h e a d t o w a r d s t h e k i d n e y s .
7 . A n d l y m p h a r e a s ( s u c h a s h e a r t a r e a , a r m p i t s , g r o i n ) .
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 83 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
1 0 . B r i e f h i s t o r i c a l o f J b o a h c r k e i g r o u n d
Johrei is a philosophy and practice, which has its foundation in a Japanese therapeutic art
developed by Mokichi Okada (1882-1955) in the early part of the last century.
Mokichi Okada was born into a poor family Okada was not a healthy youth and indeed his
various afflictions and life threatening diseases kept him from fulfilling his potential of becoming
a professional artist. Following a vegetarian diet, he gradually recovered and with the death of
his father in 1905, he became the sole supporter of his family.
He opened a small retail store in Tokyo where his artistic ability contributed to his success,
however, he was again forced to abandon this business due to illness.
During the next twenty years, the periods of success alternated with times of abysmal tragedy
and disappointment. He lost his wife and their baby due to complications during childbirth.
At one point, the failure of his main bank plunged his firm into bankruptcy, and the Great
Kanto earthquake of 1923, in addition to destroying much of Tokyo, ruined Okada financially,
along with thousands of others.
Around this time, Okada, who had been an atheist, began to search for a spiritual meaning
to life. He became acquainted with various religions and beliefs that were popular at the time,
and in this vein, in 1920, he attended a lecture on Omoto at a movie theatre, which he regularly
visited. Omoto was one of the New Religions making the headlines at the time. It is based on
Shinto, which is the oldest national religion of Japan, and much of what the lecturer said
seemed to be refreshingly straight to the point. Okada later joined Omoto and began studying
its teachings. One thing unique about Omoto was that it had its own healing ministry called
Chikon kishinho, Okada made it his own and began practicing it in 1929. However, by 1934,
dissatisfied with the limitations of religious activities and desperately wanting to reach out to all
those who needs help, he left Omoto in order to develop his gift as a healer and a therapeutic
artist.
The major influence Omoto had on Okada, was to make him realise the importance of the
Spiritual. During his time in Omoto, he also discovered that he had a special ability to heal the
sick.
He had closely studied the way in which people became ill and the way in which people
recovered from illness. He also closely studied medical writings of the day including those on
traditional medicine, and had collaborated closely with the leading medical practitioners of the
day. Through this process, he developed and perfected the unique spiritual therapy, which he
called JOHREI, meaning purification (joh) of spirit (rei)
Okada was passionate about promoting a life style, free from disease, through the use of
natural methods of preventing ourselves from becoming seriously ill. Based on his own
experience, he knew our food played a crucial role in our health.
In 1935 he began research into the possibility of realising a chemical free farming technique,
which he called Nature Farming. By the 1950’s he was able to set up experimental farms and the
Nature Farming Society.
During that period, he also created the basis for the Sangetsu School of Flower
Arrangement, which emphasised the freedom and the natural beauty of flowers. As a way of
bringing beauty into daily life, Sangetsu Flower Arrangement is also practiced alongside the
therapy of Johrei healing.
As an artist he knew that both artistic and natural beauty could inspire us and uplift our
soul. He looked for a way to bring beauty into our daily lives, and he devoted the later part of his
life to creating art museums and inspiringly beautiful gardens. The museums and the sacred
gardens he created near Mount Fuji in Hakone and the seaside resort of Atami are enjoyed by
millions of visitors today. His vision was to inspire and encourage everyone, in making this
world an Earthly paradise.
Back in 1936, Okada set up the H e a l t -care h Society of Japan and invited medical
professionals of the day, to contribute, to its promotion of a natural form of health maintenance.
This was based on a way of living that respects our body’s natural ability, to heal itself and
stresses the importance of truth, virtue and b e a u t y within health care.
The Authorities of the day did not appreciate his vision, and he was discouraged from
practicing Johrei as a therapy and healthcare measure. In order to be allowed to promote Johrei
and both the medicinal and the spiritual aspects of its teaching, he decided, in 1950, to set it up,
as a religious organisation, Sekai-Kyusei-Kyo in a style that everyone can practise Johrei.
Following his death in 1955, his teachings spread around the world, and, today, there are 3
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P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
million people practicing Johrei within families, as a natural method of maintaining health and
happiness.
This also helped the development of Nature Farming technique in countries such as Japan,
the USA, Brazil, Thailand and encouraged further research into the possibility of totally
fertiliser- and chemical - free farming techniques.
In 1996, Dr Rosy Daniel, former Medical Director of Bristol Cancer Help Centre and a
leading proponent of the holistic approach to health creation in the UK, encountered Johrei in
Japan and on her return to England, called for the formation of a Johrei society in the UK that
would re-focus its attention on the original integrity of the Johrei philosophy and teach and
promote Johrei practice, not as religion but as an individual’s truly holistic journey towards
healing and health creation.
The British Johrei Society and the Johrei Academy was formed by Dr. Rosy Daniel, Sue Boyd,
Koichi Sakakibara and Junichi Imura, as a secular organization, and on 15t h May 2001, the
British Johrei Society and the Johrei Academy were officially launched, commemorating 65t h
Anniversary of the launch of Mokichi Okada’s H e a l t -care h Society of Japan.
The British Johrei Society is currently helping to oversee scientific research, taking place
around the world, on the efficacy of Johrei. The main research is being directed by Prof. John
Gruzelier of Imperial College, University of London.
1 1 . J o h r e i p r a c t i c e
It is useful to be aware that their area three distinct styles in which Johrei is practiced:
( 1 ) J o h r e i a s d a i l y p r a c t i c e
This is the style of Johrei, which you will learn in these workshops as a way to maintain
health on daily basis. It is derived from the Therapeutic Johrei technique, which is made short
and simple so that it is easy for you to practice anywhere and at any time. By itself, it does not
constitute a therapy, however, it is a wonderful way to maintain health, prevent illness and also
to support those with chronic conditions at home.
( 2 ) T h e r a p e u t i c J o h r e i
This is the style of Johrei, which is practiced as a therapeutic intervention. A Therapeutic
Johrei practitioner will scan with hands, and use gentle touch and pressure to find the areas of
toxin accumulation and then channel the “Light” from the hand. If the toxin accumulation is
severe, Therapeutic Johrei practitioner will also use the application of finger pressure and
stroking action to encourage the movement of toxins to the kidneys, followed by channelling to
the kidneys to affect the elimination process.
The Johrei treatment is carried out with as much understanding of patient/client’s past medical
history and lifestyle as possible, so that the application of Johrei is matched to the course of the
possible Purification Process unique to the patient/client.
( 3 ) S p i r i tu al J o h r ei
This style of Johrei is practiced by those wishing to obtain closer union with their inner
spirituality and the divine. It can be likened to the induced meditation for two. It involves
channelling ‘the Light’ from the hand to the front and the back of the receiver’s body without
guiding the hand to specific areas. It is totally hands off and carried out with sincerity, love and
faith. This style of Johrei is sometimes referred as Prayer in Action.
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 85 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Appe ndi x 3 : S e l f-r e p o r t u e s q t i o n n a i r e s
S t r e s s p e r c e p t i o n
P e r c e i v e d S t r e s s S c a l e ( P S S )
S t a t e a n x i e t y s c a l e i n t h e S t a t e a n d T r a i t A n x i e t y I n v e n t o r y ( S T A I ) 288
I m p a c t o f E v e n t S c a l e E ( S I ) 289
S e n s e o f t a k i n g c o n t r o l ’s o own f o ln ife e s cal e
L o c u s o f C o n t r o l ( L o C )
Q u a l i t y o f l i f e
M e n t a l C o m p o n e n t s o f S u m m -3 a 6 r ( M y C S i ) n t h e S F 292
S l e e p q u a l i t y
P i t t s b u r g h S l e e p Q u a l i t y I n v e n t o r y ( P S Q I )
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 86 - I m p e r i a l C o l l e g e L o n d o n
287
290
295

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Pe r c e i v e St d r e s s Sc a l e
1 . In th e l as t few d a ys , h ow often h ave yo u b een
u p s et b ecaus e of s o met h i n g th at h ap p en ed
u n e x p e c t e d l y ?
2 . In th e l as t few d a ys , h ow often h ave yo u felt th at
yo u we re u n ab l e t o c on t rol t h e i mp ortan t th in gs in
y o u r l i f e ?
3 . In th e l as t few d a ys , h ow often h ave yo u felt
n e r v o u s a n d s t r e s s e d ?
4 . In th e l as t few d a ys , h ow often h ave yo u d ealt
w i t h i r r i t a t i n g l i f e h a s s l e s ?
5 . In th e l as t few d a ys , h ow often h ave yo u felt th at
yo u we re ef fect i v el y cop i n g with imp o rta n t
c h a n g e s t h a t w e r e o c c u r r i n g i n y o u r l i f e ?
6 . In th e l as t few d a ys , h ow often h ave yo u felt
con fid en t ab ou t you r ab i l i t y to h an d le yo u r
p e r s o n a l p r o b l e m s ?
7 . In th e l as t few d a ys , h ow often h ave yo u felt th at
th in gs were g oi n g you r wa y?
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 87 - I m p e r i a l C o l l e g e L o n d o n
Never
0
8 . In th e l as t few d a ys , h ow often h ave yo u fou n d
th at you cou l d n ot c op e wi t h all th e th in g s you h ad
t o d o ?
9 . In th e l as t few d a ys , h ow often h ave yo u b een
a b l e t o c o n t r o l i r r i t a t i o n s i n y o u r l i f e ?
1 0 . In t h e l as t few d a ys , h o w o ften h ave you felt
th at you wer e on t op of t h i n gs ?
1 1 . In t h e l as t few d a ys , h o w o ften h ave you b een
an gered b ecau s e of t h i n gs t h at h ap p en ed th at were
o u t s i d e y o u r c o n t r o l ?
1 2 . In t h e l as t few d a ys , h o w o ften h ave you fou n d
yo u rs el f t h i n ki n g ab ou t t h i n gs th at you h a ve to
a c c o m p l i s h ?
1 3 . In th e l as t few d a ys , h o w o ften h ave you b een
a b l e t o c o n t r o l t h e w a y y o u s p e n d y o u r t i m e ?
1 4 . In t h e l as t few d a ys , h o w o ften h ave you felt
d ifficu l t i es were p i l i n g u p s o h igh th at yo u cou ld
n o t o v e r c o m e t h e m ?
Almost never
1
Sometimes
2
Fairly often
3
Very often
4

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
S e l f-E v a l u a t i o n Q u e s t i o n n a i r e ( Y )
Dev elo p ed b y Ch a rle s D. S p i elb erge r i n col lab o rat i on wi t h R. L. G o rsu ch , R. Lu sh en e, P. R. Vag g ,
a n d G . A . J a c o b s
S T A I (-S ) F o r m -1 Y
NAME : DATE :
AGE :
T :
S E X : M / F
D I R E C T I O N S : A n u m b e r o f s t a t e m e n t s op w le h i h ave c h up se ed
to d es cri b e th ems el ves are given b elo w. R ead each s tatemen t an d
th en b lacken in th e ap p rop ri ate circle to t h e righ t o f th e s tatemen t
to in d icat e h ow you feel R I G H T , th at N is O , A W T T HIS
M O M E N T . Th ere are n o ri gh t or w ron g an s wers . Do n ot s p en d
too mu ch ti me on an y on e s tatemen t b u t give th e an s wer, wh ich
s eems to d es cri b e you r p res en t feelin g b e s t.
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 88 - I m p e r i a l C o l l e g e L o n d o n
Not at all
1 . I feel cal m. ………………………………………………………… 1 2 3 4
2 . I f e e l s e c ………….. u r e .…………………………………………… 1 2 3 4
3 . I a m t e n …………………………………………………………. s e
. 1 2 3 4
4 . I am s t rai n ed . ……………………………………………………… 1 2 3 4
5 . I feel at eas e. ………………………………………………………. 1 2 3 4
6 . I feel u p s et . ………………………………………………………. .. 1 2 3 4
7 . I a m p r e s e n t l y w o r e r py os i sn ig b le o m v i s f o r t u n e .………………. s
1 2 3 4
8 . I feel s at i s fi ed ...……………………………………………………. 1 2 3 4
9 . I f e e l f r i …………………………………………….……… g h t e n e d
1 2 3 4
1 0 . I feel c om fo rt ab l e. …………………………………………………. 1 2 3 4
1 1 . I f e e l s e -con l f fid en t . ……………………………….………………. 1 2 3 4
1 2 . I feel n er vou s . ……………………………………………………... 1 2 3 4
1 3 . I a m j i t t e r y. ……………………………………….…………….…. 1 2 3 4
1 4 . I feel i n d e .………………………………………………… c i s i v e …
1 2 3 4
1 5 . I a m rel axed . …………………………………….………………… 1 2 3 4
1 6 . I feel c on t en t ..……………………………………………………… 1 2 3 4
1 7 . I a w m o r r i …….……………………………….………………… e d
1 2 3 4
1 8 . I feel c on fu s ed ..……………………………………………………. 1 2 3 4
1 9 . I feel s t ead y. ………………….………………….………………… 1 2 3 4
20. I f e e l p lea s ant . …………………………………..………………… 1 2 3 4
S :
Somewhat
Moderately so
Very much so

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Impa c t Ev e nt Sc a l e
Name __________________________ Date ___________________
Belo w i s a l i s t of co mmen t s mad e b y p eo p le
d is tres s ed ab ou t s ome as p ect of livin g wit h
can cer. P l eas e ch eck each i te m, in d icatin g h ow
freq u en t l y t h es e c om men t s were tru e f or yo u
DUR IN G T HE P AS T S EVEN D AYS. If th e y
d i d n o t o c c u r d u r in g t h at t i me, p leas e mar k th e
‘n ot at al l ’ col u mn .
1 I thought about it when I didn’t want to.
2 I a vo i d e d l e t t i n g m ys e l f ge t upset when I
t hought a b o ut it or wa s re minde d of it .
3 I tr ie d t o re move it fr om me mo r y.
4 I h a d tr o uble f a lling a s le e p o r st a yin g a s le e p .
5 I h a d w a v e s o f s t r o n g f e e l ai bout n g s it .
6 I h a d d re a ms a bout it .
7 I st a ye d a wa y f r om re min d e rs of it .
8 I f e lt a s if it ha dn’t ha ppe n e d o r it wa s n ’t r ea l.
9 I t r i e d tn ao lk t a bo t uo t it .
10 P ict u re s a bout it popped in t o my min d .
11 Ot h er t h ings ke pt ma king me t h in k a b o u t it .
12 I wa s a wa r e that I s t ill ha d a lot of fe e lin gs
a b o u t i t , idn’t b u t de I a l wit d h t he m.
13 I tr ie d n ot t o t hink a bout it .
14 An y r e minde r br ought ba c k f ee lin gs a b o ut it .
15 M y f e e lings a bout it we r e kin d o f n u mb .
F r e q u e n c y
d u r i n g t h e p a s t w e e k
� � N o t a t a l l R a r e l y S o m e t i m e s O f t e n
0 1 3 5
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 89 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
1 5 a . I n my ca se ge t t ing wh at I wa nt h a s
lit t le o r n ot h ing to do with lu c k.
1 6 a . Who g et s t o be t he bo s s o ft en
d epe nd s on who wa s lu c ky e nou gh t o
b e in th e righ t p lac e f irs t.
1 7 a . A s fa r as wo rld a ff a irs a re con ce rne d,
mo s t of u s a re th e v ic t ims of fo rce s
we can n e it he r u nde rs ta nd , no r
c on t ro l.
1 8 a . Mo st p eop le don ' t rea liz e th e e xt en t to
wh ich the ir liv e s a re c on t ro lled b y
a c c id en ta l ha ppe n in gs .
1 9 a . On e s hou ld a lwa y s be willin g to a d mit
mis t a ke s.
2 0 a . I t is ha rd to kno w whe th e r o r no t a
p e rson re a lly lik e s yo u.
2 1 a . I n th e long run t he ba d th ing s th at
h app en t o us a re ba lan ced b y the
g ood th in g s.
2 2 a . Wit h eno ugh e f fo rt we c an wipe o ut
p o lit ic a l c o rru pt ion .
2 3 a . So met imes I c an 't u nde rs ta nd ho w
t ea ch e rs a rrive a t t he g ra de s t he y
g iv e.
2 4 a . A go od lea de r e xp e ct s pe op le to
d e c i d e f o r t eh lve e m s wha t t he y
s ho u ld d o.
2 5 a . Man y t ime s 1 fe e l th at I ha ve litt le
in f luen ce o ve r th e th ing s t ha t hap pen
t o me .
2 6 a . Pe op le a re lon e ly be cau s e th ey d on 't
t ry to b e f riend ly .
o r b . M a n y t i m e s w e m t i ag s h we t ll j de u s c ide wha t
t o do b y f lipp ing a co in .
o r b . Ge t t in g peo p le t o do t he rig ht th in g dep end s
u p o n a b i l i t y ; l u c k h a s l i t o t wit l h e o r n o t h i n g t o d
it .
o r b . B y ta k ing an a c t ive pa rt in p o lit ic a l an d so c ia l
a f fa irs t he pe op le ca n co nt ro l wo rld e v en ts .
o r b . The re rea lly is no su ch t h ing a s "lu c k . "
o r b . I t is us ua lly be s t to co ve r up on e' s mist ak es .
o r b . Ho w man y f riend s you h av e dep end s u pon h ow
n ic e a pe rso n yo u a re .
o r b . Mo st mis fo rtun e s a re t he re su lt o f la ck o f ab ilit y ,
ig no ran ce , la z ine s s , o r a ll t h re e.
o r b . I t is d if f icu lt f o r pe op le to ha ve mu ch co nt ro l
o v e r t h e t h i n g s ia p no s l do i t in i c o ff ic e.
o r b . The re is a d ire ct con ne c t ion b et we en ho w h a rd
I s tud y a nd t he g ra de s I ge t .
o r b . A go od lea de r ma ke s it c lea r t o ev e rybo dy wh at
t he ir job s a re .
o r b . I t is impo s s ib le fo r me to be lie ve t ha t ch an ce o r
lu c k p la y s an imp o rtan t ro le in my life .
o r b . The re' s no t mu ch u se in t ry in g to o ha rd to
p lea se p eop le, if th e y lik e yo u, the y like you .
2 7 a . T h e r e i s t o o m u c h e m p h a s i s o r o n b . Tea m spo rt s a re a n ex c e llen t wa y to b u ild
a th let ic s in h igh s c hoo l.
c ha ra ct e r.
2 8 a . Wha t ha ppe ns to me is my o wn o r b . So met imes I fe e l t ha t I do n' t ha ve e nou gh
d o ing .
c on t ro l o ve r t he d irec t ion my life is ta k ing .
2 9 a . Mo st o f t he t ime I can ' t und e rst and o r b . I n th e long run t he pe op le a re re spo n s ib le fo r
wh y po lit ic ian s beh av e th e way the y
b ad go ve rn me nt o n a na t ion a l a s we ll as o n a
d o.
lo c a l le ve l.
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 91 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
S F -3 6 Q u a l i t y o f L i f e ( r eS v ic s ea d l v e r s i o n )
1. I n ge n e r a l wo u ld you say your health is:� e x c e l l e n t v e r y g o o d g o o d f a i r p o o r
T i c k o n e b o x: 5 4 3 2 � 1
2 . C o m p a r e d t o o n e y e , a r h o a w g o w o u l d y o u r a t e y o u r h e a l t h i n g (T e i n e c r k a l o n n e o w b ) o ? x
M u c h b e t t e r t h a n o n e y e a r a g o
5
S o m e w h a t b e t t e r t h a n ao r n ae go y e
4
About t he s a me a s one ye ar a go
3
Some wh a t wo r s e t ha n one ye ar a go
2
M uc h wo r s e t ha n one ye ar a go
1
3 . T he f o llowing it e ms a re ab o ut a ct ivit ie s yo u migh t d o d u r in g a t yp ic a l d a y. D o es yo u r hea l t h l i m i t
you i n t h e s e a c t i v i t i e s ? I f s o , h o w m u c h ?
a ) Vigor o u s a ct ivit ie s s uc h a s r u n n in g, lif t in g h e a vy o b j e ct s ,
pa rt ic ip a t in g in s tr e nuous s por ts .
b ) M o d e r a t e a c t i v i st uc i e h s as mo vin g a t a ble , pus hing a
va c uum c le a ner , bowlin g or golf .
c ) Lif t in g or c ar r ying gr oc e r ie s .
d) Climb in g s e ve r a l f light s of st a irs .
e ) Climb in g o n e f light of st a ir s.
f ) Bendin g, kn e e ling or s t oopin g.
g ) W a or l e k t ha i n a n mile g . m
h) Wa lkin g s e ve r a l hundr e d ya r d s .
i) Wa lkin g 1 0 0 ya r ds .
j ) Bat hin g o r dr es s ing your s e lf .
Ye s ,
lim it e d
a lot 1
Ye s ,
T i c k o n e b . o x
No, not
lim it e d lim it e d
2
a l i t t l e a t a l l 3
4. Dur in g t he p a s t 4 w e e k , s ha ve yo u ha d a ny of t he f ollowin g pr ob le ms wit h yo ur wo r k or oth e r
r e gu l a r d a i l y a c t i vit ie s a s a r e s u l t o f y o u r p h ? y s i c a l h e a l t h
Y e s 1
a ) C u t d o w n t h e a m o u n t o f t i m e s p e n t o n w o r k o r o t h e r a c t i v i t i e s
b ) A c c o m p l i s h e d l e s s t h a n y o u w o u l d l i k e
c ) W e r e l i m i t e d i n t h e k i n d o f w o r k o r o t h e r a c t i v i t i e s
d ) H a d d i f f i c u l t y p e r f o r m
ing wor k o r o t h er act ivit ie s
( f o r e x a m p l e , i t t o o k e x t r a e f f o r t )
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 92 - I m p e r i a l C o l l e g e L o n d o n
N o 2

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
5 . Dur in g t he p a s t 4 w e e k , s ha ve yo u ha d a ny of t he f ollowin g pr ob le ms wit h yo ur wo r k or oth e r
r e gula r da ily a c t ivit ie s a s a r e s u l t o f a n y e m o t i o n a l p r o ( b s l u e c m h s a s f e e l i pre n g s se d e d or a nx ious) .
Y e s 1
N o 2
a ) C u t d o w n t h e a m o u n t o f t i m e s p e n t o n w o r k o r o t h e r a c t i v i t i e s
b ) A c c o m p l i s h e d l e s s t h a n y o u w o u l d l i k e
c ) D i d n ’ t do wo r k o r o t he r a ct i vi t i e s a s ca r ef ul l y a s u s u a l
6 . Du ri n g th e p a s t 4 w e e k , s t o w h a t he ave x t e you n r p h ys ical h eal th o r e moti on al p ro b lems
i n t e r f e r e d w i t h y o u r n o r m a l s o c i a l a c t i v i t i e s w i t h f a m i l y , f r i e n d s , n e i g h b o u r s o r
N o t at a l l 5
4
S l i g h t l y
3
M o d e r a t e l y
7. How much bodily pain have you had in the p a s t 4 w e e k ? s
None 6
5
V e r y m i l d
M i l d
4
M o d e r a t e 3
Q u i t e a b it 2
S e v e r e 2
1
E x t r e m e l y
1
V e r y s e v e r e
8 . Du ri n g th e p a s t 4 w e e k , s h ow mu ch d id p a i n in terfere with you r n o rmal wo rk (in clu d in g
b o t h w o r k o u t s i d e t h e h o m e a n d h o u s e w o r k ) ?
N o t at a l l 5
A l i t t l e b i t 4
3
M o d e r a t e l y
Q u i t e a b it 2
1
E x t r e m e l y
9 . Th es e q u es ti on s are ab ou t h ow you feel a n d h ow th in gs h ave b een with you d u rin g th e p as t
4 w e e k s, f or each q u es ti on , p leas e give on e an s wer th at co mes cl os es t to th e wa y you
h a v e b e e n f e e l i n g . H o w m ri u nc g h th t e i p a m s t e 4 d u w e e k s…
T i c k o n e b . o x
Al l o f Mo st o f A go o d
6
5
t h e t i m e t h e t i m e bit o f t he
t i m e
4
S o me o f A lit t le
3
t h e t i m e o f t he
t i m e
2
No ne o f
1
t h e t i m e
a ) D i d y o u f e e l f u l l o f e n e r g y ?
b) Ha ve yo u b e en a ve r y ner vou s
person?
c ) Ha ve yo u fe lt s o down in t he
dumps t h at n ot hing c ould c he er
you up?
d ) H a v e y o u f e l t c a l m a n d p e a c e f u l ?
e ) D i d y o u h a v e a l o t o f e n e r g y ?
f ) Ha ve yo u fe lt downhe ar te d a n d
s a d ?
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 93 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
g) Did you feel worn out?
h) Ha ve yo u b e en a ve r y ha ppy
person?
i ) D i d y o u f e e l t i r e d ?
j ) Ha ve yo u h ad diff ic ult y r e as o n in g
a nd solvin g p r oble ms , e .g. ma kin g
pla ns , ma kin g de c is ions , le ar nin g
n e w t h i n g s ?
k) Did yo u f o r ge t things t hat
ha ppene d r e ce nt ly e .g. whe r e yo u
p u t t h i n g s , a p p o i n t m e n t s ?
l) Did yo u h a ve t r ouble ke e ping
yo u r a t t e nt i o n on a n y a ct i vi ty f o r
long?
m) Did yo u h a ve dif f ic ult y doin g
a c t ivit ie s in vo lving c onc e ntr a t io n
and thinking?
Al l o f
6
t h e t i m e
Mo st o f A go o d
5
t h e t i m e
bit o f t he
t i m e
4
S o me o f A lit t le
3
t h e t i m e o f t he
t i m e
2
No ne o f
1
t h e t i m e
1 0 . Du ri n g th e p a s t 4 w e e k , s h ow mu ch o f th e ti me h as you r p h ys ical or em otion al p rob lems
i n t e r f e r e d w i t h y o u r s o c i a l a c t i v i s t i t e i s n g ( l f i r k i e n d s , r e l a t i v e s e t c ) ?
1
2
3
A l l o f t h e t i m M e o s t o f t h e t i m S e o m e o f t h e t i m e
A l it t le of t he t i m e
4
11. How T R U E or F A L S E i s e a c h o f t h e f o l l o w i n g s t a t e m e n t s f o r y o u ?
a ) I s ee m t o get s ic k a lit t le ea s ier th a n
ot her pe o p le .
b) I a m a s h e a lt hy a s anybody I kn o w.
c ) I e xpe ct my he a lt h t o ge t wor se .
d) M y h ea lt h is e xce lle nt .
De fin it e l y
t r u e 1
Mo st ly
t r u e 2
Do n’t
k n o w
3
Mo st ly
f a l s e
4
5
N o n e o f t h e t i m e
T i c k o n e b o x :
De fin it e l y
f a l s e
5
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 94 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
P i t t s b u r g h S l e e p Q u a l i t y I n d e x
N a m e : _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ A g e : _ _ _ _ _ D a t e : _ _ _ _ _ _ _ _ _ _ _ _ _
Th e fol l owi n g q u es ti on s rel ate t o you r u s u al s leep h ab its d u r i n g t h e p a s t . You m o n r t h
a n s w e r s s h o u l d i n d e i mos c a t e accu t rat h e rep l y for th e m a j o r i t of y d a ys o r n igh ts in th e p as t
mon th . P leas e an s wer A L L Q U E S T I O N . S
1 D u r i n g t h e p a s t m o n t h , w h e n h a v e y o u u s u a l l y g o n e t o b e d a t n i g h t ?
2 D u r i n g t h e p a s t m o n t h , h o w l o n g ( i n m i n u t e s ) h a s ? i t t a k e n y o u t o f a l l a s l e e p
3 D u r i n g t h e p a s t m o n t h , w h e n h a v e y o u u s u a l l y g o t u p i n t h e m o r n i n g ?
4 D u r i n g t h e p a s t m o n t h , h o w m a n y h o u r s o f a c t u a l s l e e p d i d y o u g e t a t n i g h t ?
( t h is m a y be d if f e r e nt f r o m t h e n u mb e r o f hou r s y o u s p e n t in be d )
5 D u r i n g t h e p a s t m o n t uld h , you h o w rate w your o sleep quality overall?
v e r y g o o d = 1 , f a i r l y g o o d = 2 , f a i r l y b a d = 3 , v e r y b a d = 4
6 D u r i n g t h e p a s t m o n t h , h o w m u c h o f a p r r o b y ol u e tm o k ee h a p s u p i t b e e n f o
e n o u g h e n t h u s ia sm t o g e t th in g s d o n e ?
No p r o b le m a t a ll = 0 ; O n ly a s lig h t p r o b lem = 1 ; So m e wh a t o f a pr o b le m =
2 ; A v e r y b ig pr o b le m = 3
7 D u r i n g t h e p a s t , m o n h t h o w o f t e n h a v e y o u h a d t
P l e a s e c h e c k t h e c o r r e c t b o x :
A C o u l d n o t g e t t o s l e e p i n 3 0 m i n u t e s
not at all
B Wo ke u p in t he midd le of t h e n i g h t o r t o o e a r l y
C Ha d to g et u p to u se the lo o.
d C o u l d n o t b r e a t h e c o m f o r t a b l y
E C o u g h e d o r s n o r e d l o u d l y
F F e l t t o o c o l d
G Fe lt t oo ho t
H H a d b a d d r e a m s
I H a d p a i n
J Ha d s we at i n g
K W e r e d i s t u r b e d b y p a r t n e r / c h i l d r e n / p e t s
l O t h e r r e a s o n s : _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
8 I n pa s t mon th , ho w o ft en d id you ta ke
m e d i c a t i o n t o h e l p y o u s l e e p ?
9 I n pa s t mon th , ho w o ft en ha ve you h ad t rou b le
s t a y ing a wak e wh ile d riv ing , ea t ing , wo rk in g o r
e n g a g i n g i n s o c i a l a c t i v i t i e s ?
less than
once a
week
1 or 2
times a
week
3 or more
times a
week
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 95 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Ap pe ndi x 4 : S t a n d a r d o p e r a t i n g p r o c e d u r e s ( S O P s )
M a t e r i a l s :
S O P -1: [ 3 H ] -t h y m i d i n e i n c o r p o r a t i o n u s i n g w h o l e b l o o d f o r p r o l i 296 f e r a t i o n a s s a y
S O P -2 : F l o w c y t o m e t r y a s s a y f o r l y m p h o c y t e p r o l i f e r a t i o n r e 297 s p o n s e i n w h o l e b l
S O P -3 : N K c e l l c y t o t o x e t i r y c a c t i v i t y 302 a s s a y b y
[ 3 H ] -T h y m i d i n e i n c o r p o r a t i o n p r o l i f e r a t i o n a s s a y p r o t o c o l i n
S O P -1 w r i t t e n b y D r . A k i r a N a i t o O c t . 2 0 0 3
B u f f e r s :
T is sue cu lt ur e me dium (T CM) c ons is ts of RPM I 16 40 s up ple men te d wit h 1 % g l u t a m i n ( e 200 mM ),
1 % p e n i c i l l 0 i 0 n I ( U 5 / 0 m l ) / s t r e p t o m y c i n ( 5 0 0 0 m -es c g s/ ent m ia l ) a, min 1 o % ac ids n o n (100 x) , 1 %
s odium pyr uva t e ( 100 mM) .
F re s h ( 1-4 hours) 1:5 d i l u t h e d p a r i n i z e d w h o l se a mples b l o ar o e d us e d f or p r o l i f e r a t i o . n T he a s s a y
blood is 1 :5 wit h t is s ue c ulture me diu m a nd 20 0 l c u l t u r e d i n t r i p l i c a -we t e l l w pla e l t e l . s o f a 9 6
M i t o g en s / A nt i gens : t h e S t a p h y l o c o c c a l e n t e r o t o x i n B -4881, ( S E Sigma-A B ) ( l p r d r o i d ®) c u h c t n o . S
and the Phytoh a e m a g g l u t i n i n A ( P -L H A ) ; ( L e c u t c i n o : a g -4144, p g r l o d u t c i t n n i o n . L P H A
S i g m a-A l d r i ®) c h a re use d as st imuli f or pr olif e ra t io n r ea ct io n (ex per ime nta l solution is t itra t e d 50 g/ ml.) .
- Fol lowin g c onc e ntr a t ion is fr om a s t oc k ( wh i c h me a ns th e REAL c on c . in t he we ll is 1/4) .
- Che mic a l ( SEB/P HA) t it r at io n : or igin a l c on ce ntr at io n is 5 mg/ ml 500, 250, to 0.78 g/ m l
D r u g p r e p a r a t i o n :
- Hyd r oc ort is one ( cort is ol) 25 0 nM (1 i n t h e a d d i n g s o l u t i o n
-
Hydr oc ort is on e t i t r a : t ( ai ddin o n g c on c entr at ions : r e a l c on ce ntr at io n in we lls a r e 1/ 4) 32 , 16 , 8 , 4 ,
2, 1, 0.5, 0.25, 0.125, 0.062, 0.031 m o l / L (underlined conce nt r at io ns a r e p h y s i o l o g i c a l . )
M e l a t o n i n
- D H E A -S
M e t h o : d
10 ml of h e p a r i n i z blood, e d 10 ml of 1 M c or t is ol, 7 ml of pre vio us ly t it r a te d ( 50 g/ L) s t imu lu s f or
1 s ubj e ct .
Pr e pa r at io n of 96 we lls p l a t e s ( o n e p l a t e f o r t w o s u b j e c t s P H A / S E r B s ) i n c u b a t i n g 7 2 h
�� �� � �� �� � �� �� � �� �� �
T C M / T C M T C M / / T C M C o Tr CM t / C o r t / M T e l C T M C 5 M 0 / C o r t / M e l 5 0 0
S E B / T C S M E B / / T C M C o SEB r / t C o r t / M e T l C S E 5 M 0 B / C o r t / M e l 5 0 0
P H A / T C P M H A / / T C M C o P HA r t / C o r t / M T e l C P H 5 M 0 A / C o r t / M e l 5 0 0
a . 50 l of stimulus (12.5 g/ m l P H A/ SE B ) i n t o a l l we l l s e x c e pt f i r s t b a c kgr o u n d we l . l
b. 50 l of e a c h dr ugs ( 0, 1 M c o r t i s o l + 0 , 2 0 0 o r 2 0 0 0 p g / m l o f m e l a t o n i n ) i n t o a l l w e l l s
c . B l o o d p r e p a r a t i o n : k e e p 5 m l E D T A t u b e f l o r y m p oc f h l yt o e w subse c y t o t s m ae na t lys r y is a s i d e
d. Mix 2 ml Li-heparinised blood with 3 ml TCM into 1:2.5 dilutions. ( 5 m l )
e . P l a c e 5 0 l of diluted whole blood o n t o e a c h w e l l ( a t t h e e n d s t e p o f p r e p a r a t i o n o f .
p l a t e s )
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 96 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
[ 3 H ] -T h y m i d i n e i n c o r p o r a t i o n p r o l i f e r a t i o n a s s a y p r o t o c o l i n
f o r -54 th d a y o f P P D s t i m u l a t -3 i o n a n d 2
r d d a y o f P H A s t i m u l a t i o n
M a t e r i a l s :
S O P -1 b w r i t t e n b y D r . A k i r a N a i t o A p r . 2 0 0 4
B u f f e r s :
T is sue cu lt ur e me dium (T CM) c ons is ts of RPM I 16 40 s up ple men te d wit h 1 % g l u t a m i n ( e 200 mM ),
1 % p e n i c i l l i n ( 5 0 0 0 I U / m l ) / ( 5 s 0 t 0 0 r e m p t c o g m / y m c l i ) n , -es 1 % s ent n ia o l n a min o ac ids (100 x) , 1 %
s odium pyr uva t e ( 100 mM) .
F re s h ( 1-4 hours) 1:5 d i l u t h e d p a r i n i z e d w h o l se a mples b l o ar o e d us e d f or p r o l i f e r a t i o . n T he a s s a y
blood is 1 :5 wit h t is s ue c ulture me diu m a nd 20 0 l c u l t u r e d i n t r i p l i c ate w e l l s o -we f la l pla 9 6 t e .
M i t o g en s / A nt i gens : t he Phytoh a e m a g g l u t i n i n A ( P -L) H A ( ; Le c t in L : e pr oduc u c t o no. a g g l u t i n i n
L-4144, Sigma-A l d r i ®: c h e xper ime nta l solution is t itr at e d 50 g / m l . ) a nd P ur if ie d pr ote in (PP D) ar e
u s e d a s s t i m u l i f o r pr o l i f er ati o n r e a c . t i o n
- Fol lowin g c onc e ntr a t ion is fr om a s t oc k ( wh i c h me a ns th e REAL c on c . in t he we ll is 1/4) .
- Che mic a l (P HA) t it ra t ion: or igin a l c on c e nt ra tio n is 5 mg/ ml 500, 250, to 0.78 g/ m l
D r u g p r e p a r a t i o n :
- Hyd r o c o rt is one ( cort is ol) 25 0 nM (1 i n t h e a d d i n g s o l u t i o n
- M e l a t o n i n 5 0 p g / m l ( 4 0 0 p g / m l i n t h
- D H E A -S
M e t h o : d
4 ml of h e p a r i n i z blood e d (10 ml of 1:2.5 diluted blood), 3 ml of 1 M c o r t i s o l 3 ml a n of d 50 pg/ml
M e la ton in , 3 ml of pre vious ly t it r a te d (5 0 g/ L P HA, 1 / 10 0 PP D) st imulus f or 1 su bj e ct .
Pr e pa r at io n of 96 we lls p l a t e s (o n e p la t e f or fo u r su b je ct s P HA / PP D) 4 p l a t e s ( 2 , 3 , 4 & 5 d a y s )
�� �� � �� �� � �� �� � �� �� �
T C M / T C M T CM / M e l T a t C o n M i n C o r t i s o l / M e l a T t o C n i M n / C o r t i s o l
P P D / T C P M P D / / T CM / T M e C l M PP D / C or t / M e l P P D / C o r t / T
�� �� � �� �� � �� �� � �� �� �
T C M / T C M T C M / M T e l C a t M o n i C n o r t i s o l / M e l a T t o C n i M n / C o r t i s o l
P H A / T C M P H A / T C M / T M C e l M PHA / C o r t / Me l P H A / C o r t / T
a . 50 l of stimulus (12.5 g/ m l P H A, o r P P D ) in t o a l l we l l s e x c e pt f i r s t b a c kgr o u n d we . l l
b. 50 l of e a c h dr ugs ( 0, 1.0 M o f c o r t i s o l a n d 0 , 2 0 0 p g / m l o f m e l a t o n i n ) i n t o a l l w e l l s
c . Bloo d pr ep a ra t ion: ( ke e p 5 ml EDT A t ub e f or f l o w c y t o m e t l r y m p oc h yt e subs e t s a n a l y s i s a s i d e )
d. Mix 2 ml Li-heparinised blood with 3 ml TCM into 1:2.5 dilutions. ( 5 m l )
e . P l a c e 5 0 l of diluted whole blood o n t o e a c h w e l l ( a t t h e e n d s t e p o f p r e p a r a t i o n o f . p l a t e s )
n d rd th th
f . P r e p a r e and 2 3 d a y p l a t e s f o r nd P H 4A a d a y p l a t e s da ( y + pla 5 t e s) f or PPD.
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 97 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
F l o w c y to me t r y a n a l y si s o f p r o l i f e r a t i o n r e s po n s e i n w ho l e b l o o d a s s a y p r o t o c o l
M a t e r i a l s :
S O P -2 w r i t t e n b y D r . A k i r a N a i t o O c t . 2 0 0 3
B u f f e r s :
T is sue cu lt ur e me dium (T CM) : RPMI 16 40 su pp le me nt e d wit h 1% g l ut a m i n e ( 200 mM) , 1%
p e n i c i l l i n ( 5 0 0 0 I U / m l ) / s t r e p t o m y c i n ( -e 5 0 s0 se 0 nt ia m l c ag min / m o l a) c, ids 1 ( 100 % x) n o , n 1%
s odium pyr uva t e ( 100 mM) .
F re s h ( 1-4 hou rs ) 1:5 diluted h e p a r i n i z e d w h o l se a mples b l o ar o e d us e d f or p r o l i f e r a t i o . n a s s a y
M i t o g en s / A nt i gens : t h e S t a p h y l o c o c c a l e n t e r o t o x i n B -4881, ( S E Sigma-A B ) ( l p r d r o i d ®) c u h c t n o . S
and the Phytoh a e m a g g l u t i n i n A ( P -L H A ) ; ( L e c u t c i n o : a g -4144, p g r l o d u t c i t n n i o n . L P H A
S i g m a-A l d r i ®) c h a r e use d as st imuli f or pr olif e ra t io n r ea ct io n (ex per ime nta l solution is titra t e d 50 g/ ml.) .
- Fol lowin g c onc e ntr a t ion is fr om a s t oc k ( wh i c h me a ns th e REAL c on c . in t he we ll is 1/4) .
- Che mic a l ( SEB/P HA) t it r at io n : or igin a l c on ce ntr at io n is 5 mg/ ml 500, 250, to 0.78 g/ m l
D r u g p r e p a r a t i o n :
- Hyd r oc ort is one ( cort is ol) 25 0 nM (1 i n t h e a d d i n g s o l u t i o n
-
Hydr oc ort is on e t i t r a : t ( ai ddin o n g c on c entr at ions : r e a l c on ce ntr at io n in we lls a r e 1/ 4) 32 , 16 , 8 , 4 ,
2, 1, 0.5, 0.25, 0.125, 0.062, 0.031 m o l / L (u n d e r l i n e d c o n c e n t r a t i o a n r e s p h y s i o l o g i c a l . )
M e l a t o n i n 5 0 p g / m l i s u p p e i r o p l h o y g s i c a l l e v e l s
- D H E A -S
M e t h o : d
T i m e c o u r s e C D 9 5 / ( A -DR) n n e xp x re i s s io n a t V CD4/ ) / CD8/ C D 2 CD5 5 / 6 in ( 0/ H 2L 4/ A 48 / 72 hr
1.
w i t h / w i t h o u t 2 5 0 n M o f H y d r o c o r t i s o n e ( c o r t i s o l ) a n d w i t h / o u t 5 0 / 5 0 0 p g / m l o f m
Pr e pa r at io n of 24 we lls p l a t e s ( o n e p l a t e f s u o b r j e ct t s w SE o B / P H A) wi t h / wi t h o u t c or t i so l
� � � �
T C M / T C M T C / M / T C M C o Tr CM t / C o r / t / T M e C l M T 5 C 0 M / C o r t / M e l 5 0 0
S E B / T C M S E / B / T C M C o SEB r t / C o r t / M T e l C S M 5 E 0 B / C o r t / M e l 5 0 0
P H A / T C M P H / A / T C M C o Pr HA t / C o r t / M T e C l M P 5 H 0 A / C o r t / M e l 5 0 0
a . 400 l o f s t i m u .5 l u s g/ m ( l 1 P 2 H A/ SE B ) i n t o a l l we l l s e x c e pt f ir s t b ac kgr o u n d we l l
b. 400 l of drug 1 (1 M c o r t i s o l / T C M ) i n t o a l l w e l l s
c . 400 l o f d r u g 2 ( 2 0 0 o r 2 0 0 0 p g / m l m e l a t o n i n / T C M ) i n t o a l l w e l l s
d. P l a c e 4 0 0 l 1:2.5 diluted whole blood ont o ea c h we ll ( 40 0 x 12 we lls = 4.8 ml needed)
2. Colle c t io n of s upe r na nt fr om c ult ure d we lls : 50 0 l f r o m e a c h w e -we l l l -pla o f t e s 2 . 4
3. Allo c a t e 500 l of mixe d s olut io n of c ult ur ed c e lls in t o 2 FAC S t ub e s .
4. S t a i n i n g
a . 5 l o f a n t i b o d i e s ( C D -C 3 D / 9 C 5 D / 8 A / n C n D e 5 x 6 i , n a -C V n D d 2 o 5 r F / I H -D F T L R C I A ) T a re C
b.
adde d to 500 l of 1:5 diluted cultured bloods.
O n e t u b e f o r i s o t y p e c o n t r o l s
c . I nc ub a te 20 min in r oom t e m p e r a t u r e
5. L y s i n g : add R B 500 C l of l y s i n g s o l u t i not o n 10x) ( 5 x a n d i n c u b a t e 2 0 m i n
F l o w c y t o m e t r y : a l w a y s m e a s u r e w i t h ( use t h s e a v e s d a m f i l e s e t t i t n g i ! s ) n g
a . R 1 i s g a t e d f o r -S SC l y s c m a t p t e h r d o ot-plot. c y t At e le as b t y 6, 0 0 F 0 S t C a r g e t c e (in l l s R1) ar e
b.
c olle c t ed per sa mple .
T h e f l u o r e s c e n c e -1 i ( F n I t T C e ) n peaks s i t a y r ce ompar o f e d F bL y ove r la ying t he his t ogr ams of d i f f e r e n t l y m p h o c p y u t l e a p t i o n s ( b y -2 g +, a FL-3+, t i n g F L -4 t + h c e lls ) F . L
c . All s a mp le s a r e te s te d in du plic a t e a nd t he re su lt s a r e pr es e nt e d a s a ve r a ge va lu e s .
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 98 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Fl owc y to me tr y a nal y si s of prol if er ati o n r e spo nse i n w ho le bloo d a ssay pr o toco l
M a t e r i a l s :
S O P -2 b w r i t t e n b y D r . A k J i u r l a y N 2 0 a 0 i 4 t o
B u f f e r s :
T is sue cu lt ur e me dium (T CM) : RPMI 16 40 su pp le me nt e d wit h 1% g l u t a m i n ( e 200 mM) , 1%
p e n i c i l l i n ( 5 0 0 0 I U / m l ) / s t r e p t o m y c i n ( -e 5 0 s0 se 0 nt ia m l c ag min / m o l a) c, ids 1 ( 100 % x) n o , n 1%
s odium pyr uva t e ( 100 mM) .
F re s h ( 1-4 hou rs ) 1:2.5 diluted h e p a r i n i z e d w h o l se a mples b l o ar o e d us e d f or p r o l i f e r a t i o . n a s s a y
M i t o g en s / A nt i gens : t he Phytoh a e m a g g l u t i n i n A ( P -L) H A ( ; Le c t in L : e pr oduc u c t o no. a g g l u t i n i
L-4144, Sigma-A l d r i ®) c h ar e us e d a s s t imuli f or pr olif er at io n re a ct io n (e x p e r i m ent a l s olut io n is
t it ra t ed 50 g/ ml.) .
- Fol lowin g c onc e ntr a t ion is fr om a s t oc k ( wh i c h me a ns th e REAL c on c . in t he we ll is 1/4) .
- Che mic a l (P HA) t it ra t ion: or igin a l c on c e nt ra tio n is 5 mg/ ml 500, 250, to 0.78 g/ m l
D r u g p r e p a r a t i o n :
- H yd r o c o r t i s o n e ( co r t i s o l) 250 nM (1 i n t h e a d d i n g s o l u t i o n
-
Hydr oc ort is on e t i t r a : t ( ai ddin o n g c on c entr at ions : r e a l c on ce ntr at io n in we lls a r e 1/ 4) 32 , 16 , 8 , 4 ,
2, 1, 0.5, 0.25, 0.125, 0.062, 0.031 m o l / L (u n d e r l i n e d c o n c e n t r a t i o a n r e s p h y s i o l o g i c a l . )
M e l a t o n i n 5 0 p g/ m l i s u p p e r p h y s i o l o g i c a l l e v e l s
- D H E A -S
M e t h o : d
rd
A n n e x i n V & P I s t a i n i n g o n C D 4 / C D 8 T c e l l s i n p r o l i f e r a t da i o y n of r e s p o n s e t o t h e P H
incubation with/out 250 nM h y d r o c o r t i s o n ( c e o r t i s o l )
H L A -D R e x p r e s s i o n a t C D 4 / C D 8 T c e l l s i n w i t h / w i t h o u t 2 5 0 n H M y d r o f c o r t i s o n e ( c o r t i s o l )
6. Pr e pa r at io n of 24 we lls p l a t e s ( o n e p l a t e f or f o u r su b j e ct s P H A) wi t h / wi t h o u t c or t i s o l
� � � � � � � �
T C M / T C T M C M / T C T M C / M M e l T CM 5 0 / C o r t / M e l 5 T 0 C M / C o r t / T
P H A / T C P M H A / T C M T C / M e l P HA 5 0 / C o r t / M e l 5 P 0 H A / C o r t /
e . 50 l of stimulus (12.5 g/ m l P H A) i n t o a l l we l l s e x c e pt f i r st b ac kgr o u n d we l l
f . 50 l of drug 1 (1 M c o r t i s o l / T C M ) i n t o a l l w e l l s
g. 50 l o f d r u g 2 ( 2 0 0 p g / m l m e l a t o n i n / T C M ) i n t o a l l w e l l s
h. P l a c e 5 0 l 1:2.5 diluted whole blood o n t o e ac h we l l
7. Allo c a t e 5 l of mixe d solu t io n of cu lt ure d c ells in t o 2 FAC S t ub e s .
8. S t a i n i n g
d. 5 l o f a n t i b o d i e /CD8, s ( C and D 3 CD95/Annexin V-F I T C
l of 1:5 dilu t e d c ult ur ed bloods.
o -D r R -F H I T L C A ) a r e e a d to d 500
e . O n e t u b e f o r i s o t y p e c o n t r o l s
f . I nc ub a te 20 min in r oom t e m p e r a t u r e
F l o w c y t o m e t r y : a l w a y s m e a s u r e w i t h ( u t s e h e s a v s e d a m f i e l e s e t t i t n i ! g s n ) g
d. R 1 i s g a t f e d o r
c olle c t ed per sa mple .
l y m p h o -S c SC y t s c a e t t e r b d ot-plot. y F S At C le as t 6, 0 0 0 t a r g e t c e (in l l s R1) ar e
e . T h e f l u o r e s c e n c e -1 i ( F n I t T C e ) n peaks s i t a y r ce ompar o f e d F bL y ove r la ying t he his t ogr ams of d i f f e r e n t l y m p h o c y t e p o p u l -2 a +, t FL-3+, i o n s F L -4 ( + b cy e lls g ) . a t i n g t h e F L
f . All s a mp le s a r e te s te d in du plic a t e a nd t he re su lt s a r e pr es e nt e d a s a ve r a ge va lu e s .
P h . D . a t U n i v e r s i t y o f L o n d o n - 2 99 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
M a t e r i a l s :
N K c y t o t o x i c a c t i v i t y a s s a y p r o t o c o l u s i n g f l o w c y t o m e t r y
S O P -3 w r i t t e n b y D r . A k i r a N a i t o F e b . 2 0 0 4
B u f f e r s :
T i s s u e c u l t u M) r e : RPMI m e 1d 640 i supple u m me ( T nt C e d wit h 1% g l u t a m i n ( e 200 mM) , 1%
pe nic illin ( 50 00 I U/ ml) / s tr e pt omyc in ( 500 0 g / m l ) , 1 % -e s se n o nt n ia l a min o a c ids ( 100 x), 1 %
s odium pyr uva t e ( 100 mM) , Lymp hP r e p (I nvit r oge n ) I n ac t iva t ed fe ta l c a lf se ru m & hu man AB
s e r u m ( -4522): S i g 56 m a H
o C fo r 35 min pr ior t o be fr oze n .
C h e m i c a l s / a n t i b o d : i e s
1 g / m l o f p r o p i d i u m i o d i n e ( P st I ) oc ( k s olu t io n wa s 1 mg/ m l : S i g m -A a l d r i ® c h p r o d u c t -4170) n o . P
and 0.05% of Eosin Y (Sigma-A l d r i ®, c h HT 1 1 0 ) f or d ye s , an t i-C D 4 5 -F I T C ®) ( , a B nt D i-C D 5 6 -P E
( B D® 555516), anti-C D 3 -A P C
M a t e r i a l s n e e d e d :
( ®) B , D H y d r o c o r t i s o n e ( -A S i l g d m r a i ® c h H-0135)
Unive r s a ls , 1 ml pipe tt es , 20 ml pip et te s , T ips ( 1ml, ye llo w) , Fla s ks ( 40 , 10 0 ml) 5 , FAC S t ub e s ,
2 4 w e l l s p l a t -b e o t t , o m , f l 9 a t-bottom), 6 w e CytoTox l l s 96® p l kit a (Pr t ome e ga ( G1 U 78 0 ) , ELI SA
k i t f o r c o r t i s o l ( p l -I a 8 8 s 7 ) m , a I s c e b & o x a s n d u i p c e
r n a t a n t s ) ( D R G
D r u g p r e p a r a t i o n :
- Hyd r oc ort is one ( cort is ol) 25 0 nM (1 M i n t h e a d d i n g s o l u t i o n
-
Hydr oc ort is on e t i t r a : t ( ai ddin o n g c on c entr at ions : r e a l c on ce ntr at io n in we lls a r e 1/ 4) 32 , 16 , 8 , 4 ,
2, 1, 0.5, 0.25, 0.125, 0.062, 0.031 m o l / L (u n d e r l i n e d c o n c e n t r a t i o a n r e s p h y s i o l o g i c a l . )
M e l a t o n i n 5 0 p g / m L i s y s i u o p l o p g e i r c a l p h c o n c e n t r a t i o n ( 2 0 0 p g / m L i n t h e a d d i n g s o l u t i o n )
- D H E A -S
C e l l p r e p a r a t i o n :
- P e r i p h e r a l b l o o d m o n o n u c l e a r c e l l s ( P B M C s )
1. Ce ntr if uge fr e sh blood a t 15 00 r pm 10 min ( 4 t ub es of 10 ml h e p a r i n i z whole e d blood)
2. Colle c t t he super nat a nt p l a s m a into 1 tube ( s t o c k i n a f r e e z e r f o r f u r t h e r s t u d y )
3. Ad d T CM t o ea c h and get t he se blo od s ont o Lymp h P re p g e n t l y w i t h g r e a . t c a r e
4. Ce ntr if uge 1500 rpm 25 min
5. C o l l e c t t h e l a y e r o f P B w M i C t h s u p p e r l a y e r
6. W a s h w C i e n t r i f h u g 1500 e T rpm C 10 M min ( w i t h K 5 6 2 f t i r c s e n t r i f u g e )
7. W a s h w i t h C e n 1 t r 0 i f % u g 1500 e F rpm C 10 S min i n ( w i t h T K 5 C 6 2 M s e c o n d c e n t r i f u g e )
8. De c a nt th e super nat a nt a nd ad d 2 m l of foe t a l c a l f s ) e + r 18 u m ml ( of F C S T C M
9. Tr a ns f er re d t o a 250 ml c ultu r e f la s k f or ‘m o n o c y t e d e p l e ’ t , i o i n c u b a 1 t HOU e R
10. C o l l e c t -a n d o h n e r e n t c e l l s f r o m f l a s k , 0 rpm c e n t 10 r min i f u g e 1 5 0
11. Add 1000 L of T CM a nd ge t 10 L of that + 90 L o f E o s i n
12. Count in microscope ( i n 1 0 o r d e : r m i n i m u m > 1 5 0 )
150 x 10 x 10 4 /ml =1.5 x 10 7 / m l add 500(=1500-1000) L of T CM
1.0 x10 7 / ml ( x1.3m l ) < P B M C s 1 >
1 t ube (T ime 0 da ta ) : 0.6 m l o f t h i < s P B M C s + 1 0.3 > m l o C f M T + 0 . 1 m l o f F C S
5.0 x 10 6 / m l ( .0ml) x 1 or 1.25 x 10 6 / m l ( x 4 . 0 m l ) c o l l e c t i n F A C S t u b e s
24-we l l -p l a t e ( i n c ub a t e ) : 0.6 ml of < P B M C s 1 > + .4 0 m l o f T C M + 0 . 3 m l o f F C S
+ 0.8 ml of 0, 50, 500 p g / m L M E L A T O N + I 0.8 N ml of 0, 250, 2500 nM CO RT I SO L
T a ke 1 ml of s upe r na nt t o s toc k a t –80 o C f o r f u r t h e r c o r t i s o l E L I S A a n a l y s i s
add 95 l o f -45 a (80 n t L i + 7 2 0 C D L o f P BS) a nd in cu bat e 20 min
13. Wa s h w i t h T C M , c e n t r 0 i rpm f u g e 6 min 1 5 0
14. Add 450 l of TCM (t o ma ke 50 0 l) and get 10 l of that + 90 l o f E o s i n ( 0 . 0 5 % E o s i n Y )
15. Count in microscope ( i n 5 o r d e r )
65 x 10 x 10 4 / m l 5 = x 6 10 5 / m l add 150 (= 65/50 x 500 -500) l o f T C M
50 x10 5 � T C M C o r t i s o C l (250 nM) 2 5 C 0 (250) 0 + Mel. n M 50 pg C (250) + Mel. 500 pg
(1) 4
/ m l o f P B M C s * (100 l ha s 50 x10 c e l l : s minimum volume needed > 600 l )
P h . D . a t U n i v e r s i t y o f L o n d o n - 3 00 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
S O P -3 : ( c o n t i n u e d )
- K 5 6 2 t u m o u r c e l l (re s q u i r 2. e 0-5.0 x 10 6 c e l l s / t o t a l )
1.
6 o
U n f r o z e n s t o c k K 5 6 2 c e l l ce s lls ( / ml 5 in x 1 0% 0 DSM O, 20% FCS, 70 % T CM at –80 C) and
c u l t u r e t h -2 e m we e 1 ks p r i o r e x pe r i m e nt st ar t . ( p as s c el s e v e r -3 y days) 2
2. Culture 10 ml of 2 x 10 5 c e l l s / m l c o n c e n t r a t i o n 2 t he d a ey xp s er p ime r i no t. r t o
3.
rd
A f t e r wash, 3 de c a n t t h e s u p e r n a t a n t a 0 n d L a of d d TCM 1 0 0
4. Get 10 L of K562 + 90 L of dye (0.05 % Eosin Y)
5. Count in microscope
50 x10 x10 4 /ml = 5 x10 6 /ml add 4(=5-1 ) m l 1.0 o x10f T C M
6 / m l < K >
1 m l o f < K > + 2 m l o f F C S + 7 m l TCM o f =1.0 x10 5 2
/ m l o f K 5 6 ) 2 i ( n * 4 0 m l c u l t u r e f l a s k
0 . 5 m l o f < K > + + 1 3.5ml m of l TCM o = f 1.0 x10 H u m a n A B s e r u m
5 3
/ m l o f K 5 6 ) 2 ( *
2 4 (2)
take 100 L o f t h i ) s ( = 1.0 ( * x10 c e l l ) s i n t o e a c h i n c u b a t i o n * * t u ( b d e u p l i c a t i o n )
ta ke 50 L of this (* 3 (3)
) into each w e l l s i -w n e l 9 6 l p l a t e ( d * u * p l i c a t i o n )
M e t h o : d
a . Fl o w a s s a y: T u b e s ( -4 1 ) f o r s e -u t p t f o i r n ac g q u i s i t i o n ( ga t i n g K 5 6 2 r e gi o n & C D 5 6 c u -o t f f )
Tube 1: take 100 L for lymph only ( f or ne ga t ive c on tr ol) + 80 L of T CM + 20 L o f F C S
Tube 2: take 100 L f or lymph on ly ( f or po s itive c on t r ol) + 80 L of T CM + 20 L o f F C S
Tube 3: take 200 L for K562** (2) o n l y f o r f l o w c y t o m e t r i c a s s a y
Tube 4: take 200 L for K562** (2) only for dupli c a t i o n
(1) (2)
E x p e r i m e n t a l t u b e s : f r om 5: M ix 100 L o f P B M C s int * o ea c h FAC S tube with K562* *
( E : T r ; a t K i 5 o 6 2 : P B M C s : 50; = * 1
(1) has 50 x10 4 c e l l ) s
1. C e n t r i f u g e a t 2 5 0 x g f o r 1 m i n
o
2. I nc ub a te 4 H O U R S i n h u m i d i f i e d i n c u b a C t , o r a f a t e r 3 7 ut t th he e n m on p I C E ! !
3. Add 3 L of CD56-P E a nt ib od y in t o e ve r y t ub e a nd in c uba t e 20 min
4. 20 L o f P I g/ ml) ( 1 a r e ad de d a n d i n c u b a t e m 1 i 0 n j u s t b e f o r e a c q u i s i t i o n
5. Add 150 l o f P B F S l o w c y t o m e t r y a c q u i s i t i o within n ( 75 s e c a c q u i s i t i o n t i m e )
b. C y t o T o x 9 6 a -b s o s t t o a m y 9 : 6 w e l u l s p l a i t e n . ( g 1 p l a U t e f o r 3 s u b j e c t s )
W e l l s : t a1 ke 50 L of K562** (3) for Max, with 50 L o f T C M ( q u a d r u p l i c a t e )
W e l l s : t a2 ke 50 L for K562** (3) only with 50 L o f T C M ( q u a d r u p l i c a t e )
We lls 3: t a ke 50 L f o r m e d i u m o n l y ( 1 0 % H u m a n A u B a d r u s p e l r i c u a m t e ) ( q
W e l l s : t a4 ke 50 L for lymph only with 50 L of T CM ( du plic a te )
(1) (3)
E x p e r i m e n t a l w e l l s : Mix 50 L o f P B M C s i * n t o e h a c we ll ha vi ng with K562* *
o
1. Centrifuge at 250 x g for 3 min and inc ub at e 4 H O U R S i n h u m i d i f i e d i n c u b a C t o r a t 3 7
2. C e n t r i e f u at g 250 x g for 3 min (600 rpm)
3. T a ke 50 L o f s u p e r n a n t a n d t r a n s f e r t o f l a t 9 6 w e l l s p l a t e ®) ( f o r L D H a s s a y :
a. F l ow c yt om e tr i c a c q u i s i t i o n :
1.
st
U s e s a v e d t e m p l a f t o r e s N K 1 C A , ( t h e n C D 5 6 d i m & b r i g h t m e a s u r e m e n t )
2. A r e g i o n 1 ( R 1 ) : S S r C e s c v e s n . c e-1 f (CD45-FI l u o T C : Fl-1 ) , t h e c l u s t e r o f t a r g e t c e l l s
3. AT LEA S T 3,000 T A R G E T C E L L (IN S R1) c o l l e c t e d p e r s a m p l e
4. T e s t e d i n d u p l i c a t e a n d t h e r e s u l t s p r e s e n t e d a s m e a n v a l u e s
b. CytoTox96® L D H m e a s u r e m e n t : s
1. De f r os t Su bs tr a te M ix, & Ad d 10 l of lysing so lu t io n in M AX qu a dr uplic a t es 45 min pr io r t o 2 .
2. Ce ntr if uge a t 250 x g f or 3 min ( 600 r pm) a nd t ra nsf er 50 l of supernant and add 50 l of
Subs t r at e M ix , t he n inc ubat e 30 min at r oo m te mp in t he dar k.
3. Add 50 l o f s t o p s o l u t i o n , a est n d #30 m on e a the s u m r a c e h i n a e t p r o g 4 r a 9 m 0 m e )
n m ! ( T
P h . D . a t U n i v e r s i t y o f L o n d o n - 3 01 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
CD5 6 NK ce ll s (di m & bri g ht) a naly si s co nc urr e ntly wi th
N K c y to t o xi c a c ti v i t y ( L D H ) a s sa y p r o t o c o l
S O P -3 b w r i t t e n b y D r . A k i r a N a i t o J u n . 2 0 0 4
M a t e r i a l s :
B u f f e r s :
T is sue cu lt ur e me dium (T CM) : RPMI 16 40 su pp le me nt e d wit h 1% g l u t a m i n ( e 200 mM) , 1%
pe nic illin ( 50 00 I U/ ml) / s tr e pt omyc in ( 500 0 g / m l ) , 1 % -e s se n o nt n ia l a min o a c ids ( 100 x), 1 %
s odium pyr uva t e ( 100 mM) , Lymp hP r e p (I nvit r oge n ) I n ac t iva t ed fe ta l c a lf se ru m & hu man AB
s e r u m ( -4522): S i g 56 m a H
o C fo r 35 min pr ior t o be fr oze n .
C h e m i c a l s / a n t i b o d : i e s
0 . 0 5 % o f E o s i n Y ( -A S i l g d m r a i ®, c h H T 1 1 0) f o r d ye s , a nt i-C D 1 6 -F I T C ®) ( , a B nt D i-C D 5 6 -P E
( B D® 555516), anti-C D 3 -C y -C h r o m e ®) , ( H B y D d r o c o r t i s o n e ( -A S i l g d m r a i ® c h H-0135),
M e l a t o n i n ( S i -A g m l a d r i ® c h -) M
M a t e r i a l s n e e d e d :
Unive r s a ls , 1 ml pipe tt es , 20 ml pip et te s , T ips ( 1ml, ye llo w) , Fla s ks ( 40 , 10 0 ml) , FAC S t ub e s ,
2 4 w e l l s p l a t -b e o t t , o m , f l 9 a t-bottom), 6 w e CytoTox l l s 96® p l kit a (Pr t ome e ga ( G1 U 78 0 ) , ELI SA
k i t f o r c o r t i s o l a n d m e l a t -I887, o n i #EIA-I n ) ( p l a s m a s & s u p e
D r u g p r e p a r a t i o n :
- Hyd r oc ort is one ( cort is ol) 25 0 nM (1 i n t h e a d d i n g s o l u t i o n )
- M e l a t o n i n 5 0 p g / m L i s u p p e r p h y s i o l o g i c a l c o n c e n t r a t i o n ( 2 0 0 p g / m L i n t h e a d d i n g s o l u t i o n )
- D H E A -S
C e l l p r e p a r a t i o n :
- P e r i p h e r a l b l o o d m o n o n u c l e a r c e l l s ( P B M C s )
1. Ce ntr if uge fr e sh blood a t 15 00 r pm 10 min ( 3. 5 t ube s of 10 ml he p a r i n i z whole e d blood)
2. Colle c t t he super nat a nt p l a s m a into 1 tube ( s t o c k i n a f r e e z e r f o r f u r t h e r s t u d y )
3. Ad d T CM t o ea c h and get t he se blo od s ont o Lymp h P re p g e n t l y w i t h g r e a . t c a r e
4. Ce ntr if uge 1500 rpm 25 min
5. C o l l e c t t h e l a y e r o f P B w M i C t h s u p p e r l a y e r
6. Wa s h w C i e n t r i f h u g 1500 e T rpm C 10 M min ( w i t h K 5 6 2 f i r s t c e n t r i f u g e )
7. W a s h w i t h C e n 1 t r 0 i f % u g 1500 e F rpm C 10 S min i n ( w i t h T K 5 C 6 2 M s e c o n d c e n t r i f u g e )
8. De c a nt th e super nat a nt a nd ad d 2 m l of foe t a l c a l f s ) e + r 18 u m ml ( of F C S T C M
9. Tr a ns f er re d t o a 250 ml c ultu r e f la s k f or ‘m o n o c y t e d e p l e ’ t , i o i n c u b a 1 t HOU e R
10. C o l l e c t -a n d o h n e r e n t c e l l s f r o m f l a s k , 0 rpm c e n t 10 r min i f u g e 1 5 0
11. Add 3000 L of T CM a nd ge t 10 L of that + 90 L o f E o s i n
12. Count in microscope ( i n 1 0 o r d e : r m i n i m u m > 1 5 0 )
150 x 10 x 10 4 / m l 1.5 = x 10 7 / m l add 1500(= (1500-1000) x 3) L of T CM
1.0 x10 7 / ml ( x1.5m l ) < P B M C s 1 >
1 t ube (T ime 0 da ta ) : 0.5 ml of < P B M C s + 1 0.5 > m l o f T C M
5.0 x 10 6 / m l ( .6ml) x 0 c o l l e c t i n F A C S t u b e s
24-we l l -p l a t e ( i n c ub a t e ) : 0.7 ml of < P B M C s 1 > + .4 0 m l o M f + T C 0 . 3 m l o f F C S
+ 0.7 ml of 0, 50 p g / m L M E L A T O N + I 0.7 N ml of 0, 250 nM C O R T I S O L
� � � �
T C M / C T o C r M t i s o l T CM 2 5 / M 0 e l at o n i n M 50 p g/ / m l C T o r C t i M s o l + M e l a t o n i n
T a ke 1 ml of s upe r na nt t o s to c k a t –80 o C f o r f u r t h e r c o r t i s o l E L I S A a n a l y s i s
13. Wa s h w i t h T C M , c e n t r 0 i rpm f u g e 6 min 1 5 0
14. Add 450 l of TCM and get 10 l of th a t + 90 l of Eosin (0.05% Eosin Y)
15. Count in microscope ( i n 5 o r d e r )
65 x 10 x 10 4 / m l 5 = x 6 10 5 / m l add 150 (= 65/50 x 500 -500) l o f T C M
50 x10 5 (1) 4
/ m l o f P B M C s * (100 l ha s 50 x10 c e l l : s minimum volume needed > 500 l )
T a ke 20 0 l of *( 1) a nd a dd 10 l o f -3-A a P n C, t CD-56-C i C D y -C h r o m e, CD1 6 = FIT C,
and N k p3 0 -P E or N k p46-P E a n t i b o d i e as nd inc ub at e 20 min ( C o n t r o l s -CD45, : N o n , F I T C
P E -CD56, Cy-C h r o m e-C D 3 , -C A P D C 8 s i n g l e s t d a i t u n b e e s )
P h . D . a t U n i v e r s i t y o f L o n d o n - 3 02 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
S O P -3 : ( c o n t i n u e d )
- K 5 6 2 t u m o u r c e l l (re s q u i r 2. e 0-5.0 x 10 6 c e l l s / t o t a l )
6.
6 o
U n f r o z e n s t o c k K 5 6 2 c e l l ce s lls ( / ml 5 in x 1 0% 0 DSM O, 20% FCS, 70 % T CM at –80 C) and
c u l t u r e t h -2 e m w e 1 e k s p r i o r e x p e r i m e n t s t a r t . -3 ( p days) a s s c e l l s e v e r y 2
7. C u l t re u 10 ml of 2 x 10 5 c e l l s / m l c o n c e n t r a t i o n 2 t he d a ey xp s er p ime r i no t. r t o
8.
rd
A f t e r wash, 3 de c a n t t h e s u p e r n a t a n t a 0 n d L a of d d TCM 1 0 0
9. Get 10 L of K562 + 90 L of dye (0.05 % Eosin Y)
10. Count in microscope
50 x10 x10 4 /ml = 5 x10 6 / ml add 4(=5-1 ) m l 1.0 o x10f T C M
6 / m l < K >
1 m l o f < K > + 2 m l o f F C S + 7 m l TCM o f =1.0 x10 5 2
/ m l o f K 5 6 ) 2 i ( n * 4 0 m l c u l t u r e f l a s k
0 . 5 m l o f < K > + f 1 m H l u m o a n + A 3.5ml B of s TCM e r = u 1.0 m x10 5 3
/ m l o f K 5 6 ) 2 ( *
2 4 (2)
take 100 L o f t h i ) s ( = 1.0 ( * x10 c e l l ) s i n t o e a c h i n c u b a t i o * n * t u ( d b u e p l i c a t i o n )
ta ke 50 L of this (* 3 (3)
) into each w e l l s i -w n e l 9 6 l p l a t e ( d * u * p l i c a t i o n )
M e t h o : d
b. Fl o w a s s a y: T ube s ( 1-4 ) f o r s e -u t p t f o i r n ac g q u i s i t i o n ( ga t i n g K 5 6 2 r e gi o n & C D 5 6 c u -o t f f )
Tube 1: take 100 L f or lymph on ly ( f or ne ga t ive c on tr ol) + 80 L of T CM + 20 L o f F C S
Tube 2: take 100 L f or lymph on ly ( f or po s itive c on t r ol) + 80 L of T CM + 20 L o f F C S
Tube 3: take 200 L for K562** (2) o n l y f o r f l o w c y t o m e t r i c a s s a y
Tube 4: take 200 L for K562** (2) o n l y f o r d u p l i c a t i o n
(1) (2)
E x p e r i m e n t a l t u b e s : f r om 5: M ix 100 L o f P B M C s int * o ea c h FAC S tube with K562* *
( E : T r ; a t K i 5 o 6 2 : P B M C s : 50; = * 1
(1) has 50 x10 4 c e l l ) s
6. C e n t r i f u g e a t 2 5 0 x g f o r 1 m i n
o
7. I nc ub a te 4 H O U R S i n h u m i d i f i e d i n c u b a C t , o r a f a t e r 3 7 ut t th he e n m on p I C E ! !
8. Add 3 L of CD56-P E a nt ib od y in t o e ve r y t ub e a nd in c uba t e 20 min
9. 20 L o f P I g/ ml) ( 1 a r e ad de d a n d i n c u b a t e m 1 i 0 n j u s t b e f o r e a c q u i s i t i o n
10. Add 150 l o f P B F S l o w c y t o m e t r y a c q u i s i t i o within n ( 75 s e c a c q u i s i t i o n t i m e )
b. C y t o T o x 9 6 a -b s o s t t o a m y 9 : 6 w e l u l s p l a i t e n . ( g 1 p l a U t e f o r 3 s u b j e c t s )
W e l l s : t a1 ke 50 L of K562** (3) for Max, with 50 L o f T C M ( q u a d r u p l i c a t e )
W e l l s : t a2 ke 50 L for K562** (3) only with 50 L o f T C M ( q u a d r u p l i c a t e )
We lls 3: t a ke 50 L f o r m e d i u m o n l y ( 1 0 % H u m a n A B s e r u m ) ( q u a d r u p l i c a t e )
W e l l s : t a4 ke 50 L for lymph only with 50 L of T CM ( du plic a te )
(1) (3)
E x p e r i m e n t a l w e l l s : Mix 50 L o f P B M C s i * n t o e h a c we ll ha vi ng wit h K562* *
o
4. Centrifuge at 250 x g for 3 min and inc ub at e 4 H O U R S i n h u m i d i f i e d i n c u b a C t o r a t 3 7
5. C e n t r i f u g e a t 2 5 0 x g f o r 3 m i n ( 6 0 0 r p m )
6. T a ke 50 L o f s u p e r n a n t a n d t r a n s f e r t o f l a t 9 6 w e l l s p l a t e ®) ( f o r L D H a s s a y :
a. F l ow c yt om e tr i c a c q ui si t i on:
5.
st
U s e s a v e d t e m p l a f t o r e s N K 1 C A , ( t h e n C D 5 6 d i m & b r i g h t m e a s u r e m e n t )
6. A r e g i o n 1 ( R 1 ) : S S C v s . f l -1 u o (CD45-FI r e s c e n c e T C : Fl-1 ) , t h e c l u s t e r o f t a r g e t c e l l s
7. AT LEA S T 3,000 T A R G E T C E L L (IN S R1) c o l l e c t e d p e r s a m p l e
8. T es te d in duplic a t e a nd t he re s ults p r e s e n t e d a s m e a n v a l u e s
b. CytoTox96® L D H m e a s u r e m e n t : s
16. De f r os t Su bs tr a te M ix, & Ad d 10 l of lys in g s olu t io n in M AX qu a dr uplic a t es 45 min pr io r t o 2 .
17. Ce ntr if uge a t 250 x g f or 3 min ( 600 r pm) a nd t ra nsf er 50 l of supernant and add 50 l of
Subs t r at e M ix , t he n inc ubat e 30 min at r oo m te mp in t he dar k.
18. Add 50 l o f s t o p s o l u t i o n , a n d a t m 490 e a s nm! u r e ( T e st #30 on the m a c h i n e p r o g r a m m e )
P h . D . a t U n i v e r s i t y o f L o n d o n - 3 03 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Appe ndi x 5: P a p e r s
i. P e e r r e v i e w e d p u b l i c a t i o n s
(1) B e n n e t t , B . M ., Lai d l aw , T. M. , Dwe vid i, P ., Naito, A., Gru zelier, J . H. (2 0 0 6 ). "A
q u a l i t a t i v e s t u d y o f t h e e x p e r i e n c e o f -h s e y l p f n o s i s o r J o h r e i i n m tatic e t a s b re as t c an cer
u s i n g i n t e r p r e t a t i v e p h e n o m e n o l o g i c a l a n a l y s i s . " C o n t e m p o - r a r y H y p n o s i s 2
1 4 0 .
(2) Lai d l aw, T. M., Nai t o, A. , Dwi ved i P ., Han s i N. K., Hen d ers on D. C ., Gru zelier J . H.
(2 0 0 6 ). "Th e In fl u en ce o f 1 0 min of th e J o h rei h ealin g met h od on lab orat or y s t res s . "
C o m p l e m e n t a r y T h e r a p i e s i n M , e d 1 i 4 c ( i 2 n ) e : -3 1 2 . 7
(3) L a i d l a w , T . , D w i v e d i , P . , N a i t o , A . , G r u z e 2 l i 0 e 0 r 5 , ). J . L o ( w s e l f-d i rect ed n es s (T C I) ,
m o o d , s c h i z o t y p y a n d h y p n o t i c s . u P s e c r e s p o t n a i l b i t l y i a t n y d I n d i v i d u a l D , i 3 f 9 f , e r e n c e
4 6 9 -4 8 0
(4) Lai d l aw, T. M., Ben n et t , B. M. , Dwe vid i, P ., Naito, A., Gru zelier, J . H. (2 0 0 5 ). Qu alit y
o f L i f e a n d M o o d C h a n g e s i n M e t a s t a t i c B r e a s t C a n c e r a f t e r t r a i n i n g -h i n yp S ne os l f is or
J oh rei. C o n t e m p o r a r y H y p n o s i s, 2 ( 2 ) : -9 8 3 4 .
(5) Gru zel i e r, J . H., De P as calis , V., J a mies on , G., Laid law, T., Naito, A. D wived i, P . ( 2 0 04 ).
R elation s b et ween h yp n ot i s ab ilit y an d p s ych op ath olo g y revis ited . C o n temp o r a r y
Hyp n o s is , 2 1 , 1 -1 6 7 9 0
(6) Lai d l aw, T. , Kers t ei n , R . , Ben n ett, B . M ., Naito, A., Dwived i , P ., Gru zelier, J . (2 0 0 4 ).
H y p n o t i zab i l i t y an d i mmu n ol ogical res p o n s e to p s ych olo gical in ter ven tion in HIV.
C o n t e m p o r a r y H y p n o s i ( s 3 , ) : 2 1 -1 1 2 36 5 .
(7) Nai t o, A., Lai d l aw, T . M. , Hen d ers on , D . C ., Farah an i, L. , D wived i, P ., Gru zelier, J . H.
( 2 0 0 3 ) . T h e i m p a c t o f s e -h l f y p n o s i s a n d J o h r e i o oc n yte l y sm u b p ph op u lat ion s at exam
time : a c on trol led s tu d y. B r a i n R e s e a r c h B u l 6 l 2 ( e t 3 ) i : n -2 2 54 3 1 .
(8) Lai d l aw, T. M., Nai t o, A. , Dwi ved i, P ., E n zor, N . A., Brin cat , C . E. Gru zelier, J . H.
( 2 0 0 3 ) . M o o d C h a n g e s a f t e r s e -H l f yp n o s i s a n d th e J o h r e i h e a l in g m e t h o d P r ior to Exa ms .
C o n t e m p o r a r y H y p n o s i ( s 1 , ) , 2 -4 0 2 0 5 .
(9) Nai t o, A., S u ga wara, H., Sh imu ra, M., A zu ma, T. , Hu jis awa, K., Ku b o, C . (2 0 0 0 )
B e h a v i o u r-t h erap eu t i c ap p roach to a p ati en t of p ain d is ord er, with a re mar kab le
a v o i d a n t -b e h a v i o u r c a u s i n g d -a i s t u s r e d o p u sh cle. y Ps yo ch of s o ma m ti c M ed icin e, 4 , 2 - 9 5
2 9 9
P h . D . a t U n i v e r s i t y o f L o n d o n - 3 04 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
i i . P r e s e n t a t i o n a n d w o r k s h o p g i v e n u n ( d e r l i n e d p e r s o n i s t h e m a i n ): s p e a k e r
1 ) You n g S ci en t i s t Da y at th e Grad u ate Sch ool of Life Scien ce an d Med icin e Stu d en t
S ymp os i u m, Lon d on , U . K. Ma y. 2 0 0 6 , “Th e in flu en ce of p s ych ol ogical in terven ti on
u p o n d i s e a s e p r o -i g n f r e c e t e s d p s a t i e o ”, n t n Naito, s i A., n Lai H d lI aw, V T ., Be n n e t t , B ,
Ba r t o n , S . , G r u z e l i e r , J . , H e n d e r s o n , D . P o s t e r s e s s i o n
2 ) 1 8 t h Worl d C on g res s on P s ych os om atic Med icin e, Kob e, J ap an . Au g. 2 0 0 5 “Th e
in flu en ce of ps ych ol o gi cal in t e r v e n t s i o up n o n s tres s rel at ed ch an ges 1 . In exa m
a s s o c i a t e d s t r n e i s v s e r s i t n y u s t u d e ” n t Naito, s A., Lai d law, T., Dwived i, P ., Gru z elier, J . ,
Hen d ers on , D . P os t er s es s i on an d p u b lished in th e J ou rn al of P s ych os om atic R es ea rch 5 8
( 2 0 0 5) , S -6 6 4 3
3 ) 1 8 t h Worl d C on g res s on P s ych os om atic Med icin e, Kob e, J ap an . Au g. 2 0 0 5 “Th e
in flu en ce of ps ych ol o gi cal in t e r v e n t s i o up n o n s tres s rel at ed ch an ges 2 . In d is eas e
a s s o c i a t e d -i n f e s c t e d r p a e t i s e ” n s t Naito, s i A., n La H i d I l a w V , T . , B e n n e t t , B . , Gr u z e er, l i
J ., Ba rt on , S ., Hen d ers on , D. P os ter s es s i on an d p u b lis h ed in th e J ou rn al of
P s y c h o s o m a t i c R e s e a r c h 5 8 ( -6 2 0 4 0 5 ) , S 6 3
4 ) 1 8 t h Worl d C on g res s on P s ych os om atic Med icin e, Kob e, J ap an . Au g. 2 0 0 5 “Stress
related ch an ges as s oci at ed with in vitr o e x p o s u r e t o c o rtis ol 1 . Effect s u p on Natu ra l
Killer cells” Nai t o, A., U g w u-O n u o h a , I., Hen d ers on , D. P os ter s es s ion an d p u b lish ed in
t h e J o u r n a l o f P s y c h o s o m a t i c R e s e a r c h -6 4 5 8 ( 2 0 0 5 ) , S 6 3
5 ) 1 8 t h Worl d C on g res s on P s ych os om atic Med icin e, Kob e, J ap an . Au g. 2 0 0 5 “Stress
r e l ated ch an ges as s oci at ed with in vitr o e x p o s u r e t o c o r t i s o - l 2 . E f f e c t s u
l y m p h o c y t e s” Nai t o , A. , Hen d ers on , D . P os ter s es s ion an d p u b li sh ed in th e J ou rn al of
P s y c h o s o m a t i c R e s e a r c h 5 8 ( -6 2 0 4 0 5 ) , S 6 3
6 ) Y o u n g S c i e n t i s t D a y a t t h e Gr a d u a t e S c h o o l o f Li f e S c ien ce an d Med icin e Stu d en t
S ymp os i u m, Lon d on , U . K. Ma y. 2 0 0 5 , “Th e in flu en ce of P s ych olo gical In ter ven ti on
u p o n N e u r -E o n d o c r i n e-I m m u n e i n t e r a ”, c t Nait i o o, n A. , Lai d law, T. , Gru zelie r, J .,
Hen d ers on , D . P os t er s es s i on
7 ) Y o u n g S c i e n t i s t D a y a t t h e ool G r of a d Li u a fe t Se ci en S c ce h an d Med icin e Stu d en t
S ymp os i u m, Lon d on , U . K. Ma y. 2 0 0 5 , “Th e in flu en ce of P s ych olo gical In ter ven ti on
u p o n d i s e a s e -i p n r f e c o t e g d r p a e t i s e ”, n s t Naito, s i o n A., Lai i dn law, T H ., I Ben V n ett, B .,
B a r t o n , S . , H e n d e r s o n , D . a n d s G t r e r u z e s l e i s e s r i , o n
J . P o
P h . D . a t U n i v e r s i t y o f L o n d o n - 3 05 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
8 ) Th e Med i cal R es earch So ciet y, th e Acad em y of Med i cal Scien ces an d th e R o ya l C ollege
of P h ys i ci an s j oi n t f ou rt h an n u al meetin g fo r C lin ician an d Scien ti s ts in Train in g,
Lon d on , U. K. Feb . 2 0 0 5 , “T h e i n f l u e n c e o f P s y c h o l o g i c a l I n t e N r e v u e r -n
o t i o n u p o n
E n d o c r i n e-Im mu n e i n t eract i on .” N aito, A., Laid law, T. M., Gru zelier , J . H., Hen d e rs on ,
D . C . P o s t e r s e s s i o n
9 ) Bri t i s h S oci et y of Im mu n olog y an n u al C on gres s , Ha rr ogate , U. K. Dec . 2 0 0 4 , “Th e
effects of 2 4 h ou rs in cu b at ion of h u man p e r i p h e r a l b l o o d u clear m o n o cel n ls wi th c ort is ol
u p on Nat u ral Ki l l e r c e l l c y t o t o x i c Naito a c t i v , i A. t , y U . g ” w u -On u oh a, I. C ., Hen d e rs on ,
D . C . P o s t e r s e s s i o n Nait ( o, A., et al . (2 0 0 4 ). Immu n ol og y 1 1 3 S u p . : 1 3 3 .
1 0 ) B r i t i s h S o c i e t y o f I m m u n o l o g y a n n u a l C o n g r e s s , H a r c r . o 2 g 0 a 0 t 4 e , “Th U e . K . D e
effects of i n cu b at i on of h u m a n p erip h eral b lood m on on u clear cell s with th e s tres s r elated
h o r m o n es, c o r t i s o l a n d m e l a t , o un pi on n i n v i t l y r m o p h o c y t e p r o l i f e r a t i v e r e s p .” o n s e s
Naito, A., H e n d e r s o n , D . C . P o s t e r s e s s i Naito, o n ( A., et al . ( 2 0 0 4). Immu n olo g y 1 1 3
S u p . 1: 1 3 3 .
1 1 ) Bri t i s h S oci et y of Exp eri men tal an d C lin ical Hyp n os is con fe ren ce, Lo n d on , J u l y 2 0 0 3 .
“H y p n o t i s a b i l i t y a n d P r o b l e m P e r s o n ” a l Laid i t i le aw, s T . M ., Dwi ved i , P ., Nait o, A.,
G r u z e l i e r , J . H . F r e e p a p e r
1 2 ) Ninth C o n g r e s s o f t h e E an u r Soci o p e et y of H yp n os is an d P s ych os omatic Med icin e,
R ome, Sep t . 2 0 0 2 , “Self-h y p n o s i s a n d J o h r e i p r a c t i c e o n i m m u n o l o g i c a l m ” e a s u r e s
Naito, A., L a i d l a w , T . M . , D w i v e d i , P . , F a r a h a n i , L . , G r u z e l i e r , J . H . F r e e p a p e r
1 3 ) N i n t h C o n g r e s s o f yp t nh os e is an d E Pu s ych r os o omat p e ia c Med n icin S o e, c i e t y o f H
R ome, Sep t . 2 0 0 2 , “P s y c h o l o g i c a l e f f e c t o f S e -h l f y p n o s i s , J o h r e i a n d R ” e l a x a t i o n
Laid law, T. M., Nai t o, A. , Dwi ved i, P ., B rin cat, C ., En zor, N., Gru zelier , J . H. Free
p a p e r
1 4 ) N i n t h C o n g r e s s o f t h e E u r o p e a n S o c si is e an t d y Po s ych f os H y omat p n o ic Med icin e,
R ome, Sep t . 2 0 0 2 , “A c o m p a r i s o n , u s i n g E E G m e a s u r e s , b e t w e e n -h S e yp l f n os is an d a
J a p a n e s e h e a l i n g ” m Dwived e t h o d i , P ., Lyn ch , C . , Laid law, T. M., Naito , A. , Gru z elier,
J . H . F r e e p a p e r
1 5 ) Nin t h C on gres s of t h e Eu rop ean Societ y of H yp n os is an d P s ych os omatic Med icin e,
R ome, Sep t . 2 0 0 2 , works h op : “J o h r e i : I n t r o d u c t o r y ” W Nait o r o, k s A. h o , p Lai d law, T.
M., Dwi ved i , P ., G r u z e l i e r , J . H . F r e e p a p e r
1 6 ) Bri t i s h S oci et y of Exp eri men tal an d C lin ical Hyp n os is con fe ren ce, Le amin gt on Sp a,
M a y 2 0 2 . “S e l f h y p n o s i s , t h e J o h r e i h e a l i n g m e t -c h on o d trol a gr n d ou r p s e : l A a x a t i o n
c o m p a r i s ” o Laid n law, T. M ., N a i t o , A . , D w i v e d i , P . , G r u z e l i e r , J . H . F r e e p a p e r
P h . D . a t U n i v e r s i t y o f L o n d o n - 3 06 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
i i i. S u p e r v i s o r f o r r e s e a r c h s t u d e n t s :
M a s t e r o f S c i e n c e r e s e a r c h p r o j e c t :
1 ) A l e x G a l e (Ev a l u a t n i of o n a ï ve, me mo r y an d regu lator y C D4 + T-c e l l s h ui man n
immu n od efi ci en c y vi ru s i n f e c t ion . K i n g s C o l l e / g e Un ive rs it y of Lon d on , MSc
I m m u n o l o g y 2 0 0 6 ).
2 ) Ije o ma U g w u -On u oh a (Th e e ffect of Str es s h ormon e, c ortis ol , on Natu ral Kille r
c e l l c yt o t o x i c a c t i v i t y a g a in s t K5 6 2 cells , i n v i . t Un r o ivers it y o f E as t Lon d on ,
M S c I m m u n o l o g y 2 0 0 4 ) . *
B a c h e l o r o f S c i e n c e r e s e a r c h p r o j e c t s :
1 ) L i n d a F a r a h a n i ( T h e E f f e c t o f S -h e l yp f n os is , J oh rei an d St res s on P erip h eral
B l o o d I m m u n e P a r a m e t e r s , I m p e r i a l C / o l U l n e i g e v e r L s o f i n d t Lon o y n d on o ,
B S c M e d i c i n e 2 0 0 2 ) . *
2 ) C h r i s t i n e B r i n c a t ( I m p a c t o f S -h e l yp f n os is an d J oh rei on P s ych ol ogical
P aramet ers in th e He al th y P op u lation , I m p e r i a l C o l l e L g o e n d o n / Un ivers it y o f
L o n d o n , B S c M e d i c i n e 2 0 0 2 ) . *
3 ) N i c k E n z o r ( I n d i v i d u a l d i f f e r e n c e s i Flexib n C o g in li i t y t an i v d e it s R el at ion s h ip to
P rofou n d St at e of R el a xat i on , I m p e r i a l C o l l e L g o e n d o n / Un ive rs it y of Lon d on ,
B S c M e d i c i n e 2 0 0 2 ) . *
4 ) Navj ot Han s i (C ort i s ol an d Mood C h anges with J oh rei after an acu te Stres s or,
I m p e r i a l C o l l L e g o e n d o n / U n i v e r s i t y d o n f , L B o S n c M e d i c i n e 2 0 0 3 ) . *
5 ) An i l Kar mal i ( An E E G s tu d y of th e J ap an es e Healin g M eth od : J oh rei, Imp erial
C o l l e g e L o n d o n / Un i ve rs i t y of Lon d on , BSc M ed icin e 2 0 03 ).
6 ) R yan Kers t ei n ( Hyp n ot is ab ilit y an d Im mu n e Statu s in HIV b lo od res u lts after
Self-h y p n o s i s o r h rei J , o I m p e r i a l C o l l e L g o e n d o n / Un ivers it y of Lo n d on , BSc
M e d i c i n e 2 0 0 4 ) . *
P ap ers h ave b een res u l t ed from th e p r oje cts mar ked with an as teri s k.
P h . D . a t U n i v e r s i t y o f L o n d o n - 3 07 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Appe ndi x 6: A d d i t i o n a l r e s u l t s
A n a l y si s of the co mpa r i so n be tw ee n Co hor ts A a n d i n B t h e s t u d e n t (3. 1. s 1 t ) u d y
T able A-1: M e a n ( 95% C.I .) P SS le ve ls of t h e C o h o r t s A and B a t t h e -e N xa o n m a nd E x am t i m e p o i n ts
Pe r c e i v e d S t r e s s S c a l e
Non-e x a m
Ex a ms
Cohort A Cohort B Cohort A Cohort B
Me a n l e ve l 19.9
22.4
24.5
27.1
( 9 5 % C . I . ) (12.7 – 27.1) (15.0 – 29.8) (18.1 – 30.9) (20.4 – 33.8)
n 8 14 8 14
T able A-2: M e a n ( 95% C.I .) St a te a nx ie t y le ve ls of the C o h o r t s o f A and B a t t h e -e N xam o n a nd Ex a m
t i m e p o i n t s
S t a t e a n x i e t y s c o r e
Non-e x a m
Ex ams Cohort A Cohort B Cohort A Cohort B
Me a n l e ve l 34.0
36.7
34.9
46.9
( 9 5 % C . I . ) (29.8 – 38.2) (33.1 – 40.3) (30.3 – 39.5) (43.7 – 50.1)
n 8 14 8 14
Table A-3: M e a n ( 9 c 5 y t % o t o x C i . c a c I t i . v i ) t y i N n C K o t h o h r e t s A a n d B a t Non-e t h e x a m a n Exa d m
t i m e p o i n ts
N K c y t o t o x i c a c t i v i t y ( % K i l l i n g )
Non-e x a m
Ex a ms
Cohort A Cohort B Cohort A Cohort B
Me a n
6.07
9.37
3.21
10.38
( 9 5 % C . I . ) (0 – 12.35) (3.88 – 14.87) (0 – 7.33) (3.09 – 17.67)
N 9 12 9 12
T able A-4: M e a n ( 9 -c 5 e ll % p e r c C e . n t a I g e . s in ) the C N o K h o r t s A and B at the Non-e x a and m Exa m
t i m e p o i n ts
N K -c e ll p e r c en t a g e
Non-e x a m
Ex a ms
Cohort A Cohort B Cohort A Cohort B
Me a n
6.36
8.86
7.34
8.71
( 9 5 % C . I . ) (3.476 – 8.87) (6.66 - 11.05) (4.20 – 10.48) (6.72 – 10. 69)
n 10 16 10 16
T able A-5: M e a n ( 9 5 % C -c . e l I l . e r ) c p e n t C a g D e 4 s i T n C t h o e h o r t s A and B at th e N o n -e xa m and Exa m
t i m e p o i n ts
CD4 T-c e l l p e r c e n t a g e
Non-e x a m
Ex a ms
Cohort A Cohort B Cohort A Cohort B
Me a n
48.54
43.88
48.29
43.24
( 9 5 % C . I . ) (43.04 – 56.04) (40.15 - 47.61) (36.72 – 54.80) (39.68 – 46.79)
n 10 16 10 16
P h . D . a t U n i v e r s i t y o f L o n d o n - 3 08 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
T able A-6: M e a n ( 95% C.I .) 8 C D T-c e ll pe rce nt a ge s in t he Cohor ts A a n d B a t t -e h e xa m N and o n Exa m
t i m e p o i n ts
C D 8 T-c e l l p e r c e n t a g e
Non-e x a m
Ex a ms
Cohort A Cohort B Cohort A Cohort B
Me a n
26.26
28.90
26.34
28.74
( 9 5 % C . I . ) (22.64 – 29.88) (26.0 6 - 31.74) (22.1 1 – 30.57) (26.0 6 – 31.43)
N 10 16 10 16
Ana ly si s of the co mpa r i so n be tw ee n S t r e s s a e nd d N o n -s t r e s s e t d u d e n ts ( 3 . 1 . 2 )
Table A-7: M e a n ( 9 5 % C . I . ) N K C A l e v e l -e s xa a m t a nd t E h e x a m N o t n i m e p o i n t s
N K C A ( % k i l l i n g )
Non-e x a m Ex ams
Me a n l e ve l
7.96
7.31
( 9 5 % C . I . ) (3.86 - 12.05) (2.61 – 12.01)
N 21 21
T a b l e A-8: M e a n ( 9 5 % -c C . e l I l . ) a n d N K C D 4 -c a e l n l d ( C % D ) 8 a T t -e t xa h m e a nd N o Ex n a m t ime
points
( % )
Non-e x a m Ex ams
Me a n NK-c e l l p e r c e n t a g e s 7.90
8.18
( 9 5 % C . I . )
(6.20 – 9.60) (6.48 - 9.88)
Me a n C D 4 -c eT ll p e r c e n t a g e s 45.7
45.2
( 9 5 % C . I . )
(42.5 – 48.9) (41.8 - 48.6)
Me a n C D 8 -c e T l l p e r c e n t a g e s 27.9
27.8
( 9 5 % C . I . )
(25.6 – 30.1) (25.5 – 30.1)
N 26 26
T a b l e A-9: Numbe r of st ude nts in th e N ot -s tre s s ed a nd S t r e s s se ubgr d ou ps wit h r e g a r to d gender who
f ille d i n t h e P S S a n d h a d b l o o d c o l l e c t i o n f o r a n d l y N m K p h C o A c y t l e v e l a n a l y s e s
( N o t e : f i g u r e s i S n t r t e h s e s e u b d g r o u p i n c l u d e o n e m a l e w h o s e r e s u l t f a i l e d t o o b t a i n f o r l y m p h o c y t e )
m a l e f e m a l e Total
N o t -s t r e s s e d 1 1 9 2 0
S t r e s s e d
1 0 1 1 2 1
T o t a l 2 1 2 0 4 1
T able A-10: M e a n (95% C.I .) N K -c e l l p e r c e n t a the g e s N ot i -s n tr e ss e d and S t r e s s subgr e d ou ps N K -c e l l (%)
Not-s t r e s s e d St re s se d
Me a n l e ve l 10.0
9.1
( 9 5 % C . I . ) (7.6 – 11.7) (6.8 – 11.4)
n 20 20
T able A-11: M e a n ( 9 5 % -c C e. ll pe I rc . e nt ) a ge s N in K the N ot -s tr e ss e d and S t r e s s m e d a l e s t u d e n t s
N K -c e l l (%)
Not-s t r e s s e d St re s se d
Me a n l e ve l 10.2
12.0
( 9 5 % C . I . ) (7.1 – 13.4) (7.9 – 16.1)
n 11 9
P h . D . a t U n i v e r s i t y o f L o n d o n - 3 09 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
T able A-12: M e a n ( 9 5 % -c C e. ll pe I rc . e nt ) a ge s N in K the N ot -s t r e s s and e d S t r e s s f e m d a l e s t u d e n t s
N K -c e l l (%)
Not-s t r e s s e d St re s se d
Me a n l e ve l 9.7
6.7
( 9 5 % C . I . ) (6.0 - 13.4) (5.2 – 8.1)
n 9 11
T a b l e A-13: M e a (95% n C. I .) le ve ls of NKCA ( % kil lin g) in t he N ot -s t r e s sed and S t r e s s f e ma d le
s t u d e n t s
N K C A (% k i l l ) i n g
Not-s t r e s s e d St re s se d
Me a n l e ve l 10.9
6.7
( 95% C . I . ) (4.9 – 16.9) (2.1 – 11.4)
n 9 11
T able A-14: M e a n ( 9 5 % C . I . ) l e v e l s o f N K C A ( % k i l l i n g ) o f m a l e a n d f e m a l e
N K C A (% k i l l ) i n g
Ma l e Fe m a l e
Me a n l e ve l 9.0
8.6
( 9 5 % C . I . ) (4.9 – 13.0) (4.9 – 12.3)
n 21 20
T able A-15: M e a ( 9 n 5% C . I .) r a ti o s o f N -c K eC ll A in t ht e Not-s o tr N es K s ed and S t r e s s f e ma d le
s t u d e n t s
N K C A to NK-c e l l r a t i o
Not-s t r e s s e d St re s se d
Me a n r a t i o 1.18
0.91
( 9 5 % C . I . ) (0.50 – 1.87) (0.23 – 1.60)
n 9 11
T able A-16: M e a n ( 9 5 % C . I . ) r -c a e t l l i o i n s m a o l f f e m a l n e N d K s t C u A d e n t t s o N K
N K C A to NK-c e l l r a t i o
m a l e f e m a l e
Me a n r a t i o 0.88
1.04
( 9 5 % C . I . ) (0.38 – 1.38) (0.56 – 1.52)
N 21 20
T a b l -17: e M eA a n (9 5% C.I .) CD4 and CD8 T-c e l l l e v e l s ( % i ) n the N ot -s t r e s s e a d n d S t r e s s subgroups e d
(%)
Not-s t r e s s e d S t r e s s e d
Me a n C D 4 -c e T l l l e ve l 44.1
47.8
( 9 5 % C . I . ) (40.0 – 48.3) (45.5 – 50.1)
Me a n C D 8 -c e T l l l e ve l 27.8
26.1
( 9 5 % C . I . ) (25.4 – 30.2) (23.7 – 28.6)
n 20 20
T able A-18: M e a n ( 9 5 % C . I . ) C D -c 4 e ll le a ve n ls d ( %) C D in 8 the T N ot -s tr e ss e d and S t r e s s ma e d le
s t ud e n t s
(%)
Not-s t r e s s e d St re s se d
Me a n C D 4 -c e T l l l e ve l 40.8
46.1
( 9 5 % C . I . ) (35.9 – 45.7) (42.7 – 49.5)
Me a n C D 8 -c e T l l l e ve l 28.5
25.2
( 9 5 % C . I . ) (24.3 – 32.6) (21.2 – 29.2)
n 11 9
P h . D . a t U n i v e r s i t y o f L o n d o n - 3 10 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
T able A-19: M e a n ( 9 5 % C . I . ) C D -c 4 e ll le a ve n ls d ( %) C D in 8 the T Not -s tr e ss e d and S t r e s s f e ma d le
s t u d e n t s
(%)
Not-s t r e s s e d St re s se d
Me a n C D 4 -c e T l l l e ve l 48.2
49.2
( 9 5 % C . I . )
(41.9 - 54.6) (46.2 – 52.2)
Me a n C D 8 -c e T l l l e ve l 27.0
26.9
( 9 5 % C . I . )
(24.9 - 29.1) (23.7 – 30.1)
n 9 11
T able A-20: M e a n (95% C.I .) C D 8 T-c e l l l e v e l s ( % ) o f m a l e a n d f e m a l e s t u d e n t s
CD8 T-c e l l l e v e (%) l s
m a l e Fe m a l e
Me a n
27.0
26.9
( 9 5 % C . I . ) (24.1 – 29.9) (25.0 – 28.8)
n 20 20
A n a l y s i s o f t h e c o m p a r i t s h e o n i n b t e r t v w e n e t e i n o n g r o u p s a n d c o n t r o l i n t h e
s t u d e n t s t u d y ( 3 . 1 . 3 )
T a ble A-21: M e a ( 9 n 5% C . I .) P SS l e ve l s i n t h e t hr ee gr o u ps at t h e E xa m t i m e p o i nt
P S S s c o r e
S e l f-h y p n o s i s J o h r e i C o n t r o l s
Me a n s c o r e 24.5
22.8
26.3
( 9 5 % C . I . ) (20.4 - 28.6) (17.5 – 28.1) (21.9 - 30.8)
N 12 11 9
T able A-22: M e a ( 9 n 5% C . I .) P SS s c o r es in m a l e s u bj e ct s i n t h e t hr e e gr o u p s a t t he E x a m t i m e p o i n t
P S S s c o r e
S e l f-h y p n o s i s J o h r e i C o n t r o l s
Me a n s c o r e 25.3
21.1
22.0
( 9 5 % C . I . ) (19.5 - 31.0) (16.6 – 25.7) (11.9 - 32.1)
N 7 7 3
T able A-23: M e a n ( 9 5 % C . I . ) P S S s c o r e s i n f e m e a t l h r e ee s gr u o b u j ps e c at t s t h e i E n xam t h t i m e p o i n t
P S S s c o r e
S e l f-h y p n o s i s J o h r e i C o n t r o l s
Me a n s c o r e 23.4
25.8
28.5
( 9 5 % C . I . ) (17.0 - 29.8) (12.9 – 38.6) (24.5 - 32.5)
N 5 4 6
T able A-24: M e a n (95% C.I .) S t a t e a n x i e t y s c t o h r e m e s a l e i s n u b j e c t s o f t h e S -hypnosis, e l f Johrei and
R e l a x a t i o n c o n t r o l g r o au t p b s a s e l i n and e t h e E x a m t i m e p o i nt
S t a t e s c o r e s i n t h e S T A I
B a s e l i n e
E x a m s
S e l f-h y p n o s i s J o h r e i C o n t r o l s S e l f-h y p n o s i s J o h r e i C o n t r o l s
Me a n s c o r e 37.8 35.9 34.3 44.4 43.8
37.0
( 9 5 % C . I . ) (32.7 - 42.8) (29.6 – 42.1) (30.2 - 38.3) (40.1 - 48.7) (39.6 – 47.9) (28.7 - 45.3)
n 8 8 4 8 8 4
P h . D . a t U n i v e r s i t y o f L o n d o n - 3 11 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
T able A-25: M e a n (95% C.I .) S t a t e s c o r e t s h e f i e n m a l e s u b j e c t s S i e n l f-hypnosis, t h e Johrei and
Re la xa t io n c ont rol gr oup at b a s e l i n and e the E x a m t i m e p o i nt
St a t e sc or e in t h e S T A I
B a s e l i n e
E x a m s
S e l f-h y p n o s i s J o h r e i C o n t r o l s S e l f-h y p n o s i s J o h r e i C o n t r o l s
Me a n s c o r e 36.6 32.8 29.7 38.8 29.5
39.2
( 9 5 % C . I . ) (33.0 - 40.2) (23.1 – 42.4) (25.9 - 33.4) (35.9 - 41.7) (24.1 – 34.9) (29.5 - 48.9)
n 5 4 6 5 4 6
T able A-26: M e a n ( 9 5% C . I .) N K C A l e ve l s ( % ki l l i n g) i n t h e t hr ee gr o u p s a t t he E x a m t i m e p o i n t
N K C A ( % k i l l i n g )
S e l f-h y p n o s i s J o h r e i C o n t r o l s
Me a n
6.0
12.9
12.2
( 9 5 % C . I . ) (0.3 - 11.7) (6.3 – 19.6) (4.4 - 19.9)
N 11 11 9
T able A-27: M e a (95% n C. I .) NKCA le ve ls ( % kill in g) in ma le s ub j ec ts in t he th r ee gr ou ps a t t he Ex a m
t i m e p o i n t
N K C A ( % k i l l i n g )
S e l f-h y p n o s i s J o h r e i C o n t r o l s
Me a n
7.3
16.2
9.8
( 9 5 % C . I . ) (0.0 - 16.0) (7.9 – 24.6) (0.0 - 23.9)
n 6 7 4
T able A-28: M e a n ( 9 5 % C . I . ) N K C A l e v e l s f( e ma % le k si ul bj l e ct i s n g in ) t he i tn hr ee gr oup s at th e Exa m
t i m e p o i n t
N K C A ( % k i l l i n g )
S e l f-h y p n o s i s J o h r e i C o n t r o l s
Me a n
4.4
7.1
14.0
( 9 5 % C . I . ) (0.0 - 12.2) (0.0 – 16.8) (4.6 - 23.4)
n 5 4 5
T able A-29: M e a n (95% C.I .) l e v e l -c s e l l o ( % f ) o f N K m a l e s t u d in e n t he t s gr ou ps o f t h e S e l -hypnosis, f
J o h r e i a n d C o n t r o at l s b a s e l i n and e t he Ex a m t i m e p o i n t
N K -c e l l s ( % )
B a s e l i n e
E x a m s
S e l f-h y p n o s i s J o h r e i C o n t r o l s S e l f-h y p n o s i s J o h r e i C o n t r o l s
Me a n l e ve l 8.9
9.5 11.8 9.4
12.6
6.6
( 9 5 % C . I . ) (6.4 - 11.3) (3.5 – 12.5) (8.4 - 15.3) (7.0 - 11.8) (9.5 – 15.8) (4.2 - 9.1)
n 7 7 5 7 7 5
T able A-30: M e a n (95% C.I .) l e v e l -c s e l l o s f ( % the N ) K f e i m n a l e s u b j e c t s i n t h e S -hypnosis, e l f Johrei
a n d R e l a x a t i o n c o n t r o l g r at o u b p a s s e l i n ae nd t he Ex a m t i m e p o i n t
N K -c e l l s ( % )
B a s e l i n e
E x a m s
S e l f-h y p n o s i s J o h r e i C o n t r o l s S e l f-h y p n o s i s J o h r e i C o n t r o l s
Me a n l e ve l 10.6 4.4
6.3
7.5
7.7
6.8
( 9 5 % C . I . ) (7.4 - 13.9) (1.0 – 7.8) (4.4 - 8.3) (1.2 - 13.9) (3.8 – 11.6) (3.4 - 10.1)
n 5 4 6 5 4 6
P h . D . a t U n i v e r s i t y o f L o n d o n - 3 12 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
T able A-31: M e a n (95% C.I .) l e v e l s f o C D 4 -c e l T l ( % ) o f m a l e t s h t e u S d e l f-h n t yp s no i s is n , J ohr e i a nd
R e l a x a t i o n c o n t r o l g r o au t p b s a s e l i n and e t he E x a m t i m e p o i nt
CD4 T-c e l l s ( % )
B a s e l i n e
E x a m s
S e l f-h y p n o s i s J o h r e i C o n t r o l s S e l f-h y p n o s i s J o h r e i C o n t r o l s
Me a n l e ve l 44.8 43.8 43.6 44.9 38.2
46.2
( 9 5 % C . I . )
n
(40.0 - 49.6)
7
(39.9 – 47.7)
7
(38.9 - 48.4)
5
(38.2 - 51.6)
7
(33.8 – 42.6)
7
(38.9 - 53.4)
5
T able A-32: M e a n (95% C.I .) l e v e l s o -c f e l l C D s 4 ( % T t ) h e f e i m n a l e s t u d e n t s i n t h e S -hypnosis, e l f
J o h r e i a n d R e l a x a t i o n c ps o n t a t r b o a l s e l g i r n o and e u t he E x a m t i m e p o i nt
CD4 T-c e l l s ( % )
B a s e l i n e
E x a m s
S e l f-h y p n o s i s J o h r e i C o n t r o l s S e l f-h y p n o s i s J o h r e i C o n t r o l s
Me a n l e ve l 46.8 51.3 46.6 47.0 51.7
47.5
( 9 5 % C . I . ) (42.4 - 51.2) (46.4. – 56.3) (41.6 – 51.6) (40.3 - 53.7) (44.4 – 58.9) (42.0 -52 9.)
n 5 4 6 5 4 6
T able A-33: M e a n (95% C.I .) l e v e l s o -c f e l l C D 8 ( % ) T o f m a l e t s h t e u S d e l f-h n t yp s no i s is n , J ohr e i a nd
R e l a x a t i o n c o n t r o l g r o au t p b s a s e l i n and e t he E x a m t i m e p o i nt
CD8 T-c e l l s ( % )
B a s e l i n e
E x a m s
S e l f-h y p n o s i s J o h r e i C o n t r o l s S e l f-h y p n o s i s J o h r e i C o n t r o l s
Me a n l e ve l 25.0 26.7 26.6 27.7 28.8
26.8
( 9 5 % C . I . ) (18.3 - 31.6) (22.3 – 31.1) (23.5 - 29.6) (22.3 - 33.2) (23.8 – 33.8) (22.2 - 31.5)
n 7 7 5 7 7 5
T able A-34: M e a n (95% C.I .) l e v e l s o -c f e l l C D s 8 ( % T t ) h fem e i n a l e s t u d e n t s i n t h e S -hypnosis, e l f
J o h r e i a n d R e l a x a t i o n c o n t r o l g ar t o b u a p s e l i n and e t he E x a m t i m e p o i nt
CD8 T-c e l l s ( % )
B a s e l i n e
E x a m s
S e l f-h y p n o s i s J o h r e i C o n t r o l s S e l f-h y p n o s i s J o h r e i C o n t r o l s
Me a n l e ve l 25.4 26.9 27.8 27.4 25.4
26.9
( 9 5 % C . I . ) (17.6 - 33.4) (24.6 – 29.3) (23.0 – 32.5) (22.5 - 32.3) (23.6 – 27.3) (22.7 - 31.1)
n 5 4 6 5 4 6
Ana ly si s of the co mpa r i so n be tw ee n Str e ss pe rc e ptio n a nd the di sea se pa ra me te r s
i n -i H n I f e c V t e d i n d i v i d u a l s ( 3 . 2 . 1 )
T able A-35: C o r r e l a t i o n b e t w e e n CD4 t h g e r a d i e n t ( c e l per l s l pe r m o n t h ) a n d t st h re e s s pe r ce pt ion
s c o r e s a n d t h e p e r c e i v e d q u -of-l a l i f t e y a t r e c r u i t m e n t t i m e p o i n t ( p r e ) a n d -mont f o u r hs af te r t he
r e c r u i t m e n t ( p o s t )
S t a t e a n x i e t y I E S P S S LoC MC S P S Q I
pre post pre post pre post pre post pre post pr e post
R .15 .28 .28 .19 .14 .18 .32 .02 - .24 .15 .22 - .03
2-t a ile d p N S N S N S N S N S N S 0.085 N S N S N S N S N S
N 30 30 30 30 30 30 30 30 30 30 30 30
NS: p > 0 . 1
P h . D . a t U n i v e r s i t y o f L o n d o n - 3 13 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
T able A-36: C o r r e l s a t b e i t o w n e e n t h e C D 4 g r a d i e n t per ( c e l l s pe r m o n t h ) a n d t h e c h a s n c g o e r e s of
s t re ss p er c ep t i o n s c a l es i n :
S t a t e a n x i e t y I E S P S S
R .13 - .18 .02
2-t a ile d p N S N S N S
n 30 30 30
NS: p > 0 . 1
T able A-37: Number of H I V-i n f e c t e d i n d i vi d u a ls who had vi r a l l o a d l e ve l c he c k
a t t h e m o n t h l y e r i t o i d s m f e r m p o t h e R e cr u i t m e n t t o four months af te r t he re c ru it me nt (Ter m 4)
V a l i d n u m b e r
N P er ce n t
T e r m 4 ( f o u r m o n t h s a f t e r t h e R e c r u i t m e n t t i m e p o i n t ) 10 15.9%
T e r m 3 ( t h r e e m o n t h s a f t e r t h e R e c r u i t m e n t t i m e p o i n t ) 17 27.0%
T e r m 2 ( t w o m o n t h s a f t e r t h e R e c r u i t m e n t t i m e p o i n t ) 17 27.0%
T e r m ( 1 o n e m o n t h a f t e r t h e R e c r u i t m e n t t i m e p o i n t ) 14 22.2%
B a s e l i n e ( 2 w e e k s b e f o r e a n d a f t e r t h e r e c r u i t m e n t ) 18 28.6%
T able A-38: Co r r e la t ion be t we e n t he vi r a l l o a d l e ve l gr a d i e n ts (log-t r a nsf or med vir a l c op ies per l pe r
m o n t h ) a n d t h s e t r e s s p e r c and e p t the i o n p e r c e i v e d q u -of-l a l i t f e y s c o r e at s re c ru it me nt t ime point ( pr e )
a n d f o u r m o n t h s l a t e r ( p o s t )
S t a t e a n x i e t y I E S P S S LoC MC S P S Q I
pre post pre post pre post pre post pre post pre post
R .04 .04 .25 .04 - .02 - .01 .21 .03 - .09 .08 .20 .11
2-t aile d p N S N S N S N S N S N S N S N S N S N S N S N S
n 29 29 29 29 29 29 29 29 29 29 29 29
NS: p > 0.1
T able A-39: Co r r e la t ion be t we e n t he vi r a l l o a d l e ve l g r a d i e n t log-t ( r a ns f or me d c opie s per l pe r mo nt h )
a n d t h e c h a n g e s c o r e s o f p e r c e i v e d s t r e s s a -of-l n d q i u f a e l i s t c y o r : e s i n
S t a t e a n x i e t I y E S P S S LoC M C S P S Q I
R - .02 - .30 - .08 - .13 .29 - .15
2-t a ile d p N S N S N S N S N S N S
n 29 29 29 29 29 29
NS: p > 0 . 1
T able A-40: C o r r e l a t i o n b e tt he w N e K e n g r a d i e n t ( c e per l l s l pe r m o n t h ) a n d t s h t e r e s s p e r c e p t i o n s c o r e s
and the p e r c e i v e d q u -of-l a l i f t e y a t r e c r u i t m e n t t i m e p o i n t ( p r e ) a n d -mont f o u r hs af te r t he re c r uit me nt
( p o s t )
S t a t e a n x i e t y I E S P S S LoC MC S P S Q I
pre post pre post pre post pre post pre post pr e* post
R .26 .19 .01 - .04 .20 .11 .28 .17 - .30 - .24 .44 .28
2-t a ile d p N S N S N S N S N S N S N S N S N S N S 0.017 N S
N 29 29 29 29 29 29 29 29 29 29 29 29
NS: p > 0.1; *: p < 0.05
T able A-41: Co r r e la t ion be t we e n t he N K g r a d i e n t ( c e per l l s l pe r m o n t h ) a n d t h e c h a n g e s c o r e s o f
p e r c e i v e d s t r e q s u s a l a i n -of-l t d y i f e s c o r : e s i n
S t a t e a n x i e t y I E S P S S LoC M C S P S Q I
R - .19 - .07 - .23 - .16 .11 - .22
2-t a ile d p N S N S N S N S N S N S
N 29 29 29 29 29 29
NS: p > 0 . 1
P h . D . a t U n i v e r s i t y o f L o n d o n - 3 14 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
A n a l y s i s o f t h ee e n t h c e o m p i a n r t i e s r o v n e n b t e i t o w n g -r
o u p s a n d
i n f e c t e d i n d i v i d u a l s ( 3 . 2 . 2 )
Table A-42: M e a n (95% C.I .) le ve ls of t he St a t e a nx iet y a n d P S s S c o r e s -individ i n ua t ls h in e t he H I V
S e l f-h y p n o s i s , J o h r e wa i i t-l a n i d s t co e d n t r o l g r o u p s a t t h e B ost-i a s e n t l e r i v n e n e t i o a n d t i m t e h p e o i n P t s
B a s e l i n e
P os t -i n t e r v e n t i o n
S e l f-h y p n o s i s J o h r e i C o n t r o l s S e l f-h y p n o s i s J o h r e i C o n t r o l s
Me a n A n x i e t y 41.5
( 9 5 % C . I . ) (24.6 - 5 8 . 4)
35.7
(25.0 - 4 6 . 4)
43.4
(30.2 - 5 5 . ) 6
37.6
(25.0 - 5 0 . 2)
35.9
(24.8 - 4 7 . 0)
42.4
(29.2 - 5 5 . 6)
Me a n P S S
( 9 5 % C . I . )
31.8
(24.5 - 3 9 . 1)
31.3
(24.8 - 3 7 . 8)
31.7
(24.4- 39.0)
30.6
(24.9 - 3 6 . 3)
32.1
(27.2 - 3 7 . 0)
31.8
(26.7 - 3 8 . 7)
N 21 12 18 21 12 18
T able A-43: M e a n (95% C.I .) le ve ls of t he L o C , M C S a n d P S Q in I the HIV-i n d i v i d u a l s i n t h e S -e
l f
hyp n o s i s , J oh r e i an d wa i t-l i s t e d c o n t r o l g r o au t p t s h e B a s e l i and n e P o st -i n t e r v e n t i o n t i m e p o i n t s
B a s e l i n e
P os t -i n t e r v e n t i o n
S e l f-h y p n o s i s J o h r e i C o n t r o l s S e l f-h y p n o s i s J o h r e i C o n t r o l s
Mean LoC 10.2 12.0 11.2
9.4 11.3 11.2
( 9 5 % C . I . ) (9.3 - 1 1 . 1) (10.8 - 1 3 . ) 2 (10.2 - 1 2 . 2) (8.4 - 1 0 . 4) (10.0 - 1 2 . 6) (10.2 - 1 2 . 2)
Me a n M C S 43.0 46.7 39.7 47.4 48.0 39.5
( 9 5 % C . I . ) (40.0 - 4 6 . 0) (42.8 - 5 0 . 6) (36.5 - 4 2 . 9) (44.6 - 5 0 . 2) (44.5 - 5 1 . 5) (36.6 - 4 3 . 4)
Me a n P S Q I 9.2
8.6 9.4
8.5
7.5 9.6
( 9 5 % C . I . ) (8.4 - 1 0 . 0 ) (7.6 - 9 . 6) (8.6 - 1 0 . 2) (7.8 - 9 . 2) (6.6 - 8 . 4) (8.9 - 1 0 . 3)
n 21 12 18 21 12 18
T able A-44: M e a n (95% C.I .) le ve ls of r e g r e s s i o n g r a d i v e i n r t a s l i l n o a d l e v -t e rl a ns s fo ( r me L o g d) i n
H I V-i n f e c t e d i n d i v i d u a l s i n t h e S -hypnosis, e l f J o hr e i a nd wa i t -l i s t e d c o n t r o l g r o u p s
H I V-v i r a l l o a d l e -t v e r l a n s f o ( r m l e o d g )
S e l f-h y p n o s i s J o h r e i C o n t r o l s
Me a n c h a n g e - .016
- . 0 2 1 - . 0 3 1
( 9 5 % C . I . ) (- .053 t o + .019) (- .082 t o + .040) (- .077 t o + .014)
N 14 12 12
T able A-45: M e a n (95% C.I .) le ve ls of r e g r e s sio n gr a die nt s in N K -c e l l (counts per l p e r m o n ) t i h n
i n f e c t e d i n d i v i d u a l s i n t h e S -hypnosis, e l f J ohre i a nd wa i t -l i s t e d c o n t r o l g r o u p s
N K -gr a die nt (counts pe r l p e r m o n ) t h
H I - V
S e l f-h y p n o s i s J o h r e i C o n t r o l s
Me a n c h a n g e - 2.4
+ 2 . 8 - 1 . 3
( 9 5 % C . I . ) (- 9.4 t o + 4.7) (- 5.9 t o + 11.4) (- 9.1 to + 6.5)
n 15 10 12
P h . D . a t U n i v e r s i t y o f L o n d o n - 3 15 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
Appe ndi x 7: R e s e a r c h p r o p o s a l f o r p o s -d t o c t o r i a l p r o j e c t
I n v e s t i g a t i o n o f s t r e s s m a n a g e m e n t i n , HIV J o pat h r i e nt i s , u p o n H e a
n o t r e c e i v i n g a n t i-re t r o v i r a l tr e a t m e nt ( A R T ) : A n O p e n S t u d y
B a c k g r o u n d
A k i r A a I T O N M . D . 2 0 0 6
Johrei i s a J a p a n e s e s t r e s s m a n a g e m e n t s y s t e m w h i c h p t ra r o ining v i d e a s n d e n c o u r a g i n g t pra h e ct ic e
o f s e l f-h e lp c op ing st r at e gie s f o r d e a l i n g w i t h s . t r O e s u s r r e c e n t r e s e a r c h s t u [ N d i a e i t s o e t a l . , 2 0 0 ha 5 ] ve
s h o w n t h a t t h e p r o g r e s -c s ei ll cv oe unt s d in e HI c l V i inf n ee ct e d i pat n ie nC ts D , wh 4 ic T h is a s s oc ia te d
w i t h 'i l l-h e a l t h ' , w a s i n ru t e p r t e d i n p a t i e n t s t r a i n e d i n a n d p r a c t i s i n g J o h r e i s . Io t v e r a p e r i o d o
i s b e l i [ e C v a e t d a l a n e t a l . , 1 9 9 5 ] t h a t t h e m a i n t -c e en lls a ove n c r e t his o f ive f months C D 4 per T io d wil l
h a v e b e n e f i t e d t h e p a t i e n t s b y p r o l o n g i n g t h e p e r i o d ing o f t he ' og no se o t d of h HI e a V l t h ' a n d d e l a y
r e l a t e d c o m p l i c a t i o n s a n d e d t for h e s pn ec e if ic HI V tr ea t ment .
P u r p o s e
T he c ur r e n t st u d y i s p r op o se d t o :
M e t h o d
Su b j e c t s
Conf ir m th e p r e v i o u s f i n d i n ; g s
D e m o n s t r a t e i n H I V p a t i e n t s t h a t J o h r e i i m p r o v ; e s q u a l i t y o f l i f e
D e t er m i n e i f J oh r e i p a r t i c u l a r l y a f f e s c t u -p b s o p u C l D a 4 t i o n s s u c h a e, s n m a e ï m v o r y a n d
r e g u l a t -c e o l r l s; y a T n d
I de nt if y o n the ba s is of spe c if ic p s yc h o lo gic a l a n d immu n o lo gic a l p r o f ile s wh ic h p a t ien t s wo u ld
b e n ef i t f r o m pr a ct i s i n g J o h r e i.
P at i e nt s w i t h H I V w h o -c h e a l v l e c o C u n D t 4 m T o r e t h a n 2 0 0 c e l l s p e r m a ri e c not r o l i t t r e a n d w h o
r e ce i vi n g a n t i-r e t r o vi r a l tr e a t me n t ( ART ) wil l b e re c ru it e d b y c omple t in g t h e wr it t e n c o ns ent for m.
S t u d y d e s i g n
O p e n cohort s t u d y c o m p a r e d w i t h c o n c u r r e n t a n d h i s -ma t o r t che i c a d l ( a ge c a , s ge e nder a nd CD4
c o u n t s ) c o n t r o l p a t i e n t s s e l c linic e c t ae l d da tf ab r ao se m of t re h s ults .
J o h r e i i n t e r v e n t i o n
T r a i n i n g o f J oh r e i , a J ap a n es e s t r es s m a na ge m e n t s yst e m wh i c h p r o vi d e s :
C o r e p h i l o s o p h i e s a n d p r i n c i p l e s f o r J o ; h r a e n i d p r a c t i c e
B a s i c t e c h n i q u e s : m e n t a l i m a g e o f h e a l i n g l i g h t ing a n td he t ligh a k t i fn rom g t he u r n s a t r e c e i v
i m a g i n a r y s o u r c e a n d c h a n n e l l i n g i t t o t h e -touching r e c i p i hand. e n t w i t h t h e n o n
J ohre i c a n b e pr ac t is ed individu a ll y b u t is b et te r in p a ir s an d h en c e p at ie n ts wil l b e e n c ou r age d t o
a t t e n d t h e t r a i n i n g s e s s i o n w i t h d t o h i pra s / c th ise e r J ohre p a r i wit t n h e r his / a he n r par t ne r .
P h . D . a t U n i v e r s i t y o f L o n d o n - 3 16 - I m p e r i a l C o l l e g e L o n d o n

P s ych ol o gi cal in ter ven ti on an d psy c h o -n e u r o-e n d o c r i n -i o mmu n e n et wo rk. A k i r A a I T O N
O n e w e e k e n d t r a i n i n g t ( e n hours e x cluding two one-hour lunch b r e a k s) a n d f i v e - m o n t h l y f
ups (1.5-2 hours e ac h) wit h pr a ct ic e at ho me a min imu m o f f o ur 2 0 min s e ss io n s pe r we e k mo nit o r ed
b y a s e l f-r e p o r t r e c o rd.
M e a s u r e s
P r i m a r y o u t c o m e
As s e s s m e n t -c o f e l l C D 4 d e T c l i n e r a t e f r o m -c p er ll o c os unt p e s ac t t one i to v e t wo r o u t i n e C D 4
m o n t h i n t e r v a l s d u r i n g t h e s t u d y p e r i o d a n d , w h -e
r e a p p r o p r i
c e ll c ou nt s o ve r t he pre c eding s ix to 12 months.
S e c o n d a r y o u t c o m e s
1. I m m u n o l o g i c a l p a r a m e t e r s on ( t hr e e oc ca s ions a longs ide r ou t in e c l i n i l c a m o n i t o ) r i n g
N a ï v e and M e m o r y CD4 T-c e l l s and R e g u l a t -c o e r l y l T s u b p o p u l a t i o n
2. P s yc ho l o gi c a l que s t ionna ir es ( be fo r e a nd t h r e e a n d m s o i n t x h s a f t e r t h e t r a i n i n g : )
S t r e s s p e r c e p t : i o P n e r c e i v e d S t r e s s [ S C c o h r e n e t a 83] l . , 1 9
P er ce i ve d s o c i a l s up p o r t : K e ss e l e r P er c e i ve d So c i a l Su p p o r t [ C o v e n t r y e t a l . , 2 0 0 4 ]
Q u a l i t y o f L i f e ( e r m p e o n w t e ) : S e n s e o f C o h e [Antonovsky, r e n c e 1993]
Q u a l i t y o f L i f e ( s p i r i t u a l : i t S y p ) i r i t u a l I n v o l v e m e n t a n d B e l i [ H e f a s t c h S c e a t l a e l . , 1 9 9 8 ]
Sleep qual i t y : P i b t u t r s g h S l e e p Q u a l i t [ y B u I y s n s d e e e x t a l . , 1 9 8 9 ]
3. P er so n a lit y que st ionna ir e ( o n ly a t r e cr u i t m e nt ) :
C l o n i n g e r T e m p e r a m e n t a n d C h a r a c t [ e C r l o n I i n g v e r n t e t o r a l y . , 1 9 9 3 ]
4. Fi n a n c i a l / Ec onomic a l a na lys e s (o ve r th e s i x m o n t h s) :
R e c r u i t m e n t
T h e c o s t e f f e c t i v e r a t i o a n a [ H l y l s a e t s k y e t a l . , 2 0 0 4 ]
84 J ohr e i p a r t i c i p a n t s w i l l b a e n d r c e o c m r p u a i r e t d e d w i t h d a t a b a s e c o n . t Tr his o l s numb er wa s
c a lc ula te d at 5% s ignif ic a nce a nd 9 0% po we r o n t he ba s is of th e pr e vio us f in din g t ha t 5 8% of
s ubje ct s in t he J o h r e i g r o u p s t a y e d t h e s a m e -ce o ll r c ou nt i c n o c m r p a e r a e d s e w d i t h i n t h e i r
33% o f s u bj e cts in t h e c o n t r o l . g r o u p
D a t a c o l l e c t i o n
Q u e s t i o nn a i r es : b e f o r e a n d t a t h r e o n e t h s a f n t d e r J s o h i r e x i t m r a i n i n g
B l o o d s a m p l e s : an a d d i t i o n a l 1 7 m l b l o o d s a m p l e w i l t l t he b se a me t a tk ime e n pa a t ie nt s c ome for
A n a l y s e s
mont hly r o u t ine monit or ing c he c ks , at mo nt h z e r o, t hr ee a nd s ix .
T he re s u lts wil l be s ta t ist ic a lly a n a lys e d b y r egr e s s io n , co rr e la t ion , a na lys e s o f va r ia n c es
( AN O V A) a n d s t u d e nt t-t e s t u s i n g t h e S t a t i s t i c a l P a c k a g e f o r S o c i a l S c i e n c e s ( and S P S S the )
S t a t i s t i c a l A n a l y s i s S o f t w a r e ( S A .
S )
P h . D . a t U n i v e r s i t y o f L o n d o n - 3 17 - I m p e r i a l C o l l e g e L o n d o n