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Biol Psychiatry. 2007 Jul 1;62(1):72-80. Epub 2007 Jan 9.

Effect of tryptophan hydroxylase-2 gene variants on suicide risk in major depression.

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1
McGill Group for Suicide Studies, Douglas Hospital Research Center, Montreal, Canada.

Abstract

BACKGROUND:

Suicide and depressive disorders are strongly associated, yet not all depressed patients commit suicide. Genetic factors may partly explain this difference. We investigated whether variation at the tryptophan hydroxylase-2 (TPH2) gene and its 5' upstream region may predispose to suicide in major depressive disorder (MDD) and whether this predisposition is mediated by impulsive-aggressive behaviors (IABs).

METHODS:

We genotyped 14 single nucleotide polymorphisms (SNPs) in 259 depressed subjects, 114 of which committed suicide while depressed. Phenotypic assessments were carried out by means of proxy-based interviews. Single-marker and haplotype association analyses were conducted. Differences in behavioral and personality traits according to genotypic variation were investigated, as well as genetic and clinical predictors of suicide.

RESULTS:

We found two upstream and two intronic SNPs associated with suicide. No direct effect of these variants was observed on IABs. However, a slight association with reward dependence scores was found. Controlling for suicide risk factors, two SNPs (rs4448731 and rs4641527) significantly predicted suicide, along with cluster B personality disorders and family history of suicide.

CONCLUSIONS:

The TPH2 gene and its 5' upstream region variants may be involved in the predisposition to suicide in MDD; however, our findings do not support the role of IABs as mediators.

PMID:
17217922
DOI:
10.1016/j.biopsych.2006.09.008
[Indexed for MEDLINE]
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