Tryptophan hydroxylase 1 gene polymorphisms alter prefrontal cortex activation during response inhibition.

The tryptophan hydroxylase 1 gene (TPH1) catalyzes the formation of 5-hydroxytryptophan, a precursor to the neurotransmitter serotonin. Variations in the gene encoding this enzyme may underlie difficulties in impulse control; however, the proximate relationship between risk alleles for polymorphisms in the TPH1 gene and the neural correlates of response inhibition remain poorly understood. The present study examined the relationship of 2 single nucleotide polymorphisms in the TPH1 gene (rs1799913 and rs4537731) to prefrontal cortex (PFC) activation on a response inhibition task. Evoked hemodynamic oxygenation in the PFC was measured in 30 unrelated healthy adult women using 16-channel continuous-wave functional near-infrared spectroscopy while they completed a manual go/no-go task. TPH1 alleles showed no association with demographic characteristics, general intelligence, impulsive personality traits, or accuracy and response latency indices on the go/no-go task. Participants carrying the risk alleles, however, showed less activity primarily in bilateral inferior frontal gyri and medial PFC under conditions of response inhibition. Polymorphisms in the TPH1 gene may be represented by diminished activity in lateral areas of the PFC underlying response inhibition. Reduced activity in medial PFC might represent altered self-monitoring of performances on the response inhibition task.