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.
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.
Authors: M Mercedes Perez-Rodriguez; Shauna Weinstein; Antonia S New; Laura Bevilacqua; Qiaoping Yuan; Zhifeng Zhou; Colin Hodgkinson; Marianne Goodman; Harold W Koenigsberg; David Goldman; Larry J Siever Journal: J Psychiatr Res Date: 2010-05-06 Impact factor: 4.791
Authors: Maria A Oquendo; Gregory M Sullivan; Katherin Sudol; Enrique Baca-Garcia; Barbara H Stanley; M Elizabeth Sublette; J John Mann Journal: Am J Psychiatry Date: 2014-10-31 Impact factor: 18.112
Authors: Guo-Lin Chen; Melinda A Novak; Jerrold S Meyer; Brian J Kelly; Eric J Vallender; Gregory M Miller Journal: Horm Behav Date: 2009-11-06 Impact factor: 3.587
Authors: Linda Booij; Richard E Tremblay; Marco Leyton; Jean R Séguin; Frank Vitaro; Paul Gravel; Elisabeth Perreau-Linck; Mélissa L Lévesque; France Durand; Mirko Diksic; Gustavo Turecki; Chawki Benkelfat Journal: PLoS One Date: 2010-06-22 Impact factor: 3.240