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

Biol Psychiatry. 2007 Jul 1;62(1):72-80. doi: 10.1016/j.biopsych.2006.09.008. Epub 2007 Jan 9.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aggression / psychology
  • Depressive Disorder, Major / enzymology*
  • Depressive Disorder, Major / genetics*
  • Depressive Disorder, Major / psychology
  • Family
  • Female
  • Genetic Predisposition to Disease / genetics
  • Genetic Variation*
  • Humans
  • Impulsive Behavior / genetics
  • Impulsive Behavior / psychology
  • Linkage Disequilibrium
  • Male
  • Pedigree
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Suicide / psychology
  • Suicide / statistics & numerical data*
  • Tryptophan Hydroxylase / genetics*


  • TPH2 protein, human
  • Tryptophan Hydroxylase