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

Abstract

Objective: 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. Method: 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. Results: 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. Conclusions: 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.