Impact of tryptophan hydroxylase 2 G-703T polymorphism on anger-related personality traits and orbitofrontal cortex

Genetic variation in human tryptophan hydroxylase 2 (TPH2) influences TPH enzymatic activity and is associated with emotion-related traits and mood disorders. The present study investigated the effect of the TPH2 G-703T polymorphism on regional brain volume, assessed using voxel-based morphometry (VBM), and anger traits in mentally healthy individuals. We examined 63 healthy subjects to investigate structural abnormalities using a 1.5-T magnetic resonance imaging system, which was normalized to a customized T1 template and segmented with VBM. The VBM data were analyzed using an analysis of covariance, with age as a covariate. All subjects were assessed with the state-trait anger expression inventory (STAXI) and genotyped for TPH2 G-703T. The subjects with GIG genotype had significantly higher anger control (AX-Con) anger scores than T allele carriers (G/T and T/T genotype). There was a negative correlation between the anger out (AX-Out) and trait anger (T-Ang) scores and gray matter concentration (GMC) in the inferior orbitofrontal cortex (OFC) and hippocampus. Compared to T allele carriers, subjects with the G/G genotype had significantly lower GMC in the inferior OFC. Our findings suggest that OFC is an intermediate phenotype that bridges serotonin synthesis and anger-related traits. The mechanism underlying the effect of the TPH2 gene on OFC abnormality, however, may be complex and may involve several processes related to anger expression. (c) 2012 Elsevier B.V. All rights reserved.