Modulation of anger control in suicide attempters by TPH-1

A genetic association between the tryptophan hydroxylase gene (TPH)-1 A218C polymorphism and suicidal behaviour is supported by numerous case-control studies as well as recent meta-analyses. Some data suggest that this polymorphism could also influence individual differences in anger-related personality traits, a phenotype partially under genetic control and known to increase the risk of suicide ideation and attempt. The aim of the present study was to investigate whether the TPH-1 A218C polymorphism affected anger-related personality traits in suicide attempters (n = 544). We hypothesized that suicide attempters carrying the AA genotype would display different scores on a scale measuring anger-related traits compared with suicide attempters carrying the CC genotype. Indeed, the dimension of Anger Control was significantly affected by the TPH-1 A218C polymorphism: suicide attempters carrying the AA genotype scored significantly lower on the Anger Control subscale than suicide attempters carrying the AC and CC genotypes. This polymorphism did not display any influence on the other State-Trait Anger Expression Inventory subscales. This result confirms our working hypothesis and suggests that the TPH-1 genotype could confer a vulnerability to suicidal behaviour through a reduced capacity to control anger, which in turn may represent a common psychopathological and behavioural pathway to suicidal behaviour in an important subgroup of clinical subjects.