A functional variant of the tryptophan hydroxylase 2 gene impacts working memory: a genetic imaging study

Imaging studies have demonstrated that prefrontal and parietal regions are activated during working memory (WM) tasks. Recently some molecular genetic studies reported associations between a functional promoter polymorphism of the tryptophan hydroxylase 2 gene (TPH2), that regulates the synthesis of serotonin, and attention. In 49 healthy Caucasian subjects the role of the TPH2 -703 G/T polymorphism for WM was tested by means of an imaging genomics approach in an n-back task. fMRI data showed an increased activation for the 2-back as compared to the 0-back condition for a large network in prefrontal and parietal areas. Although behavioural data showed no performance differences between the genotype groups of the -703 G/T a significantly stronger activation of the TT genotype carriers in BA 6, BA 46, and BA 40 was visible in contrast to the GT and GG groups. Present findings in congruence with previous findings support the hypothesis that TT carriers compensate deficits in executive control functions by increased brain activity.