Possible association between response inhibition and a variant in the brain-expressed tryptophan hydroxylase-2 gene

The ability to inhibit a response is an important component of normal behavioral control and is an aspect of psychopathology when diminished. Converging evidence implicates the serotonergic neurotransmitter system in response inhibition circuitry. Objectives The present study examined potential associations between serotonergic genetic markers and response inhibition as indexed by Stop Task performance. Methods College-age participants (N= 199) completed self-report questionnaires, the computerized Stop Task, and donated buccal cells for genetic analyses. Statistics were analyzed by ANOVA. Results Stop Signal reaction time was not associated with allelic variation at a monoamine oxidase A promoter length polymorphism or a serotonin I B terminal autoreceptor polymorphism (G861C). An intronic genetic marker of the neuronal tryptophan hydroxylase-2 (the rate-limiting enzyme for serotonin biosynthesis) gene, however, was associated with the Stop Signal reaction time. Individuals homozygous for the T variant at an intron-8 polymorphism had the longest Stop Signal reaction time (i.e. greater impulsivity, P=0.01), and this effect was stronger in males (P=0.01) than in females (P=0.10). Conclusions A genotype at an intron-8 tryptophan hydroxylase-2 polymorphism was associated with response inhibition as indexed by the Stop Task. These results, if replicated, would implicate dorsal raphe serotonin neurons in response inhibition. It may be that individuals with the T/T genotype may have reduced tryptophan hydroxylase-2 function and correspondingly lower central serotonin levels; however, further investigation of the reported association is required.