XI Congresso della Società Italiana di Psicopatologia Psichiatria ...

The Serotonin Hypothesis of Obsessive
Compulsive Disorder: an Update
J. Zohar
Sheba Medical Center, Division of Psychiatry, Tel-
Hashomer, Israel
OCD is unique with regard to treatment response. As opposed
to other psychiatric disorders such as depression, panic
disorder, post traumatic stress disorder, ecc., in which noradrenergic
and serotonergic medications were found to be
effective, OCD seems to respond preferentially to serotonergic
medications 1 2 .
In a double-blind, placebo controlled study an exacerbation
of obsessive compulsive symptoms was reported following
oral administration of the serotonin agonist
methylchlorophenylpiperizine (mCPP) 3 . These findings,
that were replicated in another four studies 2 , were interpreted
as indicating behavioral hypersensitivity of the
serotonergic receptors in OCD patients. It is important to
note that other anxiogenic challenges, such as lactate, carbon
dioxide, yohimbine and cholicystokonine receptor agonists
were not associated with an exacerbation of OC
symptoms. Taking together these positive and negative
findings suggests that OCD patients are not sensitive to all
anxiogenic challenges, but only to 5HT challenges.
By analyzing the behavioral response to other pharmacological
challenges (such as MK-212 and isapirone), a possible
role of the 5HT 1D receptor, densely located in the basal
ganglia, in OCD has been posed 4 .
Preliminary data with the 5HT 1D agonist sumatriptan supported
this hypothesis. Case reports, in which prolonged administration
of sumatriptan was associated with therapeutic
effects, provide additional support for the potential role of
5HT 1D in obsessive compulsive symptoms 5 6 .
Recently published genetic data indicating polymorphism of
5HT 1Dβ in OCD patients 7 replicate the already existing data
on the role of 5HT 1Dβ in OCD 2 . Dimensionally speaking,
5HT 1D might actually be implicated in repetitive behavior 8 .
Newer compounds such as zolmitriptan, which is also a
5HT 1D agonist, and is safe for human use (it has, like sumatriptan,
an approval as anti-migraine medication) might be
used in a pharmacological challenge to further elucidate the
potential role of 5HT 1D in OCD.
The real challenge, however, is to link the pharmacological
challenge in sophisticated behavioral setting along with the
genetic findings and brain imaging reactivity (as an additional
marker) in order to harness the potential of 5HT 1D in OCD.
References
1 Zohar J, Insel TR. Obsessive-compulsive disorders; psychobiological
approaches to diagnosis, treatment and pathophysiology.
Biol Psychiat 1987;22:667-87.
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SIMPOSI TEMATICI
22 FEBBRAIO 2005 - ORE 14.15-15.45
SALA CAVALIERI 2
S2 - Lo stato dell’arte nella terapia del Disturbo
Ossessivo Compulsivo
MODERATORI
L. Bellodi, J. Zohar
2 Zohar J, Kennedy JL, Hollander E, Koran L. Serotonin-1D hypothesis
of obsessive-copmpulsive disorder: an update. 2004.
3 Zohar J, Mueller EA, Insel TR, Zohar-Kadouch RC, Murphy
DL. Serotonergic responsivity in obsessive-compulsive disorder:
comparison of patients and healthy controls. Arch Gen Psychiatry
1987;44:946-51.
4 Zohar J. Is 5HT1D involved in obsessive compulsive disorder? IX
ECNP Congress 1996, p. 4-54 (abstract S.26.02).
5 Stern L, Zohar J, Cohen R, Sasson Y. Treatment of severe,
drug resistant obsessive-compulsive disorder with the 5HT1D agonist sumatriptan. Eur Neuropsychopharmacol 1998;8:325-
8.
6 Pathak S, Cottingham EM, McConville. The use of sumatriptan
in the treatment of obsessive compulsive disorder in an
adolescent. J Child Adolesc Psychopharmacol 2003;13(Suppl
1):S93-4.
7 Mundo E, Richter MA, Zai G, McBride J, Macciardi F,
Kennedy JL. 5HT1D receptor gene implicated in the pathogenesis
of obsessive compulsive disorder: further evidence
from a family-based association study. Molecul Psychiatry
2002;7:805-9.
8 Hollander E, Pallanti S. 5HT1D function and repetitive behaviors.
Am Psychiatry 2001;158:972-3.
The role of dopamine in Obsessive-
Compulsive Disorder: an update
D. Denys
The Rudolf Magnus Institute of Neuroscience, Department
of Psychiatry, University Medical Center, Utrecht, The
Netherlands
Obsessive compulsive disorder (OCD) is a chronic psychiatric
disorder characterized by recurrent persistent
thoughts (obsessions) and/or repetitive compulsory behaviors
(compulsions).
Over the past two decades, it has been suggested that OCD
might be related to the functioning of brain serotonin systems,
mainly because of the anti-obsessional efficacy of
selective serotonin inhibitors (SRIs). In recent years, there
is growing evidence that the dopamine system may be involved
in OCD as well. In this presentation, the preclinical
and clinical evidence supporting the role for dopamine in
the pathophysiology of OCD will be reviewed.
Evidence for the involvement of dopamine in OCD may be
obtained from animal models, measurements of dopamine
and metabolite concentrations, pharmacochallenge and
pharmacotherapeutic studies, and neuro-imaging, and genetic
association studies.
The role of dopamine will be highlighted at the background
of current OCD paradigms.