Polymorphism in serotonin transporter gene associated with susceptibility to major depression

doi:10.1016/S0140-6736(96)90079-3

The Lancet

Volume 347, Issue 9003, 16 March 1996, Pages 731-733

https://doi.org/10.1016/S0140-6736(96)90079-3 Get rights and content

Abstract

Summary

Background The serotonin transporter of the brain provides the primary target for the action of selective antidepressant drugs. We set out to identify polymorphisms of the serotonin transporter gene and to find out whether there was a relation between any such polymorphisms and the occurrence of affective disorder.

Methods A comparison of a polymorphic region of the human serotonin transporter gene was carried out between two groups. The study group comprised 83 patients (39 unipolar depressive disorder, 44 bipolar disorder) with major affective disorder. The control group comprised 122 anonymous blood donors, and 71 volunteers who had been screened for psychiatric disorders.

Findings We detected three novel alleles of the variable-number-tandem-repeat (VNTR) region (STin2.9, STin2.10,and STin2.12) containing nine, ten and 12 copies of the VNTR element, respectively. The frequencies of the different forms of the allele in the control group were compared with those in the affective disorder group. There was a significant difference between the control and affective disorder groups, largely explained by the excess of the STin2.9 allele in the unipolar group (χ²=10·05, p<0·004 [Bonferroni corrected]). The presence of the allele with nine copies of the repeat was significantly associated with risk of unipolar disorder (odds ratio=6·95 [95% Cl 1·8-27·2]).

Interpretation This association, for an obvious candidate gene, may provide a critical starting point for an understanding of the likely polygenic contributions towards susceptibility to affective disorder.

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Early reportsPolymorphism in serotonin transporter gene associated with susceptibility to major depression

Abstract

Biol Psychiatry

Lancet

The efficacy of selective serotonin re-uptake inhibitors in depression: a meta-analysis of studies against tricyclic antidepressants

J Psychopharmacol

Antidepressant- and cocaine-sensitive human serotonin transporter: molecular cloning, expression, and chromosomal localisation

Proc Natl Acad Sci USA

Primary structure of the human platelet serotonin (5-HT) uptake site: identity with the brain 5-HT transporter

J Neurochem

Organisation of the human serotonin transporter gene

J Neural Trans

Diagnostic and statistical manual of mental disorders

Early reports
Polymorphism in serotonin transporter gene associated with susceptibility to major depression