Influence of functional tryptophan hydroxylase 2 gene variation and sex on the startle response in children, young adults, and older adults

Serotonin, a key regulator of emotional behavior, is synthesized by tryptophan hydroxylase (TPH). Allelic variation of TPH2 gene expression influences serotonin synthesis in the brain and therefore may modulate emotional processing. Here, we investigated the influence of the −703 G/T polymorphism in the regulatory promoter region of the TPH2 gene on the startle response in three different age samples: children (N = 110), young adults (N = 209), and older adults (N = 95). Startle magnitudes to intense noise bursts were recorded during baseline and while participants viewed unpleasant, pleasant or neutral pictures. There was a significant TPH2 × sex interaction effect in young adults with male T allele carriers showing stronger overall startle responses compared to male G/G homozygotes while in young women this effect appeared to be reversed. The difference between TPH2 genotype groups also reached significance in the female subsample when including menstrual cycle phase. In contrast, there was no effect of TPH2 or a TPH2 × sex interaction effect in children or in older adults.