Effect of tryptophan hydroxylase-2 gene variants on suicide risk in major depression.
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.
Lopez de Lara
Catalina
C
McGill Group for Suicide Studies, Douglas Hospital Research Center, Montreal, Canada.
Brezo
Jelena
J
Rouleau
Guy
G
Lesage
Alain
A
Dumont
Mimi
M
Alda
Martin
M
Benkelfat
Chawki
C
Turecki
Gustavo
G
D000293:Adolescent; D000328:Adult; D000374:Aggression / Q000523:psychology; D003865:Major Depressive Disorder / Q000201:enzymology* / Q000235:genetics* / Q000523:psychology; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D007175:Impulsive Behavior / Q000235:genetics / Q000523:psychology; D015810:Linkage Disequilibrium; D008297:Male; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013405:Suicide / Q000523:psychology / Q000706:statistics & numerical data*; D014365:Tryptophan Hydroxylase / Q000235:genetics*
C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase