TY  - JOUR
PY  - 2007//
TI  - Effect of tryptophan hydroxylase-2 gene variants on suicide risk in major depression
JO  - Biological psychiatry
A1  - Turecki, Gustavo
A1  - Benkelfat, Chawki
A1  - Alda, Martin
A1  - Dumont, M.
A1  - Lesage, Alain
A1  - Rouleau, Guy A.
A1  - Brezo, Jelena
A1  - Lopez de Lara, Catalina
SP  - 72
EP  - 80
VL  - 62
IS  - 1
N2  - 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.<p />  <p>Language: en</p>
LA  - en
SN  - 0006-3223
UR  - http://dx.doi.org/10.1016/j.biopsych.2006.09.008
ID  - ref1
ER  -