ABSTRACTS - World Psychiatric Association

suppression of the immune system in depression which is reversed
with recovery.
PO1.193.
MODELLING G PROTEIN-MEDIATED
SIGNAL TRANSDUCTION IN IMMORTALIZED
HUMAN LYMPHOCYTES IN RESPONSE
TO ANTIDEPRESSANT TREATMENT:
POSSIBILITIES FOR DEVELOPING
PATIENT-SPECIFIC PHARMACOTHERAPY
S. Hodgkinson, J. Kirchheiner, W.P. Kaschka
University of Ulm, Germany
Perturbations in the mechanisms governing the uptake and release of
neurotransmitters such as serotonin, norepinephrine and dopamine
in the brain have been implicated in the aetiology of affective disorders.
A number of antidepressant drugs are available that inhibit the
uptake of one or more of these neurotransmitters. However, relatively
little is known about the pharmacogenetic determinants of this
inhibition. A better understanding of how individual patient genotypes
influence the efficacy of these drugs will provide the opportunity
for earlier, more targeted therapeutic interventions to be made.
Immortalized human lymphocytes express a number of neurotransmitter
receptors and transporters on their cell surface membrane, and
thus provide a simple model system for the study of neurotransmitter
uptake and release. We describe the first stages of our approach for
combining mathematical modelling of the molecular processes
involved in the uptake and release of serotonin, dopamine and norepinephrine
by immortalized human lymphocytes, with experimental
work looking at the changes in signal transduction that occur in the
lymphocytes in response to a number of reuptake inhibitor antidepressants.
An outline of the underlying mathematical model is provided,
together with some initial findings from our experimental
work. This approach provides a powerful means of testing and adapting
basic mathematical models of cellular function (such as membrane
transport and sequestration) using experimental data generated
from the same model system.
PO1.194.
FETAL GROWTH RESTRICTION
AND THE DEVELOPMENT OF MAJOR DEPRESSION
H.-M. Vasiliadis, S.E. Gilman, S.L. Buka
Department of Community Health and Sciences, University
of Sherbrooke, Quebec, Canada; Departments of Epidemiology
and of Society, Human Development and Health, Harvard School
of Public of Health, Boston, MA, USA; Department
of Community Health, Brown University, Providence, RI, USA
Whether or not lower birth size is associated with a higher risk of
depression in adulthood is not clear, as prior studies have reported
varying results. This study aimed to test the association between fetal
growth restriction and the lifetime risk of major depression and number
of recurrent episodes. Study subjects (n=1101) were offspring of
participants in the Providence, Rhode Island, site of the National Collaborative
Perinatal Project. Cox regression was used to investigate the
relation between measures of birth size and the lifetime risk of depression,
and the mean number of depressive episodes was compared
across categories of birth size. There was no association between low
birth weight, gestational age, ponderal index, and small for gestational
age and the lifetime risk of major depression, or the number of
recurrent episodes. These results suggest that fetal growth restriction,
as reflected by multiple measures of birth size, is not associated with
the risk of a major depression or the subsequent recurrence of depressive
episodes. They do not support a “fetal programming” effect in
depression.
PO1.195.
QUALITY OF LIFE AND PERSONALITY TRAITS
MODERATE THE INFLUENCE OF SEROTONIN
TRANSPORTER GENETIC VARIANTS ON
DEPRESSIVE SEVERITY AND TREATMENT
OUTCOME IN BIPOLAR SPECTRUM DISORDERS
L. Mandelli, M. Mazza, G. Martinotti, D. Tavian, E. Colombo,
S. Missaglia, D. De Ronchi, R. Colombo, L. Janiri, A. Serretti
Department of Psychiatry, University of Bologna; Department
of Psychiatry and Institute of Biochemistry and Clinical
Biochemistry, Catholic University, Gemelli Hospital, Rome;
Laboratory of Human Molecular Biology and Genetics, Catholic
University, Milan, Italy
In the present work we aimed to test the effect of serotonin transporter
gene (SLC6A4) variants on depressive outcome in combination with
personal/interpersonal well-being indexes and personality traits. One
hundred and thirty patients with a bipolar spectrum diagnosis were
included in the sample. At intake, patients were evaluated for personality
traits, depressive symptoms, quality of life (QoL) and social
adjustment (SAS), and then followed for a period of 1 year under
pharmacological treatment. Evaluations were repeated after 1, 3, 6 and
12 months of treatment. Four SLC6A4 variants were genotyped:
SERTPR, the SERTPR A/G variant (rs25531), rs25533 and STin2
(VNTR in intron 2). Indicators of psychosocial adjustment (QoL and
SAS), as well as personality traits, particularly Harm Avoidance (HA),
significantly and strongly correlated with depressive severity at various
stages of the follow-up. Controlling for confounders and covariates,
SLC6A4 variants (SERTPR *S or *LG, rs25533 *T, STin2 *12 and the
S-T-12 haplotype) were significantly associated with baseline depressive
severity and poor outcome during treatment. A good QoL
markedly favour subjects carrying risk variants, while a high HA
showed an opposite effect, increasing depressive scores and reducing
remission likelihood. These findings are a further confirmation of an
influence of SLC6A4 on depression and its outcome. Most importantly,
QoL and HA moderate genetic associations, suggesting an interactive
effect between these variables and SLC6A4 variations.
PO1.196.
ELECTROCONVULSIVE THERAPY INCREASES
SERUM GLIA CELL LINE-DERIVED NEUROTROPHIC
FACTOR IN DRUG RESISTANT DEPRESSED
PATIENTS
Xiaobin Zhang, Zhijun Zhang, Weiwei Sha, Chunming Xie,
Guangjun Xi, Honghui Zhou, Yumei Zhang
Department of Neurology, Affiliated ZhongDa Hospital
of Southeast University, Nanjing; Department of Psychiatry,
Affiliated WuTaiShan Hospital of Yangzhou University,
Yangzhou, China
Electroconvulsive therapy (ECT) is effective for patients with antidepressant
medication-resistant depression. However, the mechanisms
of ECT’s effectiveness for treating depression are not fully understood.
We investigated if ECT operates a modulation of serum glial
cell line-derived neurotrophic factor (GDNF) levels in a sample of
drug resistant depressed patients. There was a significant increase of
serum GDNF levels in responders to ECT (before ECT: 401.7±193.2
pg/ml; 5 weeks after starting ECT: 686.2±299.2 pg/ml; p=0.033),
204 World Psychiatry 8:S1 - February 2009