Family-based association study of tryptophan hydroxylase 2 and serotonin 1A receptor genes in attention deficit hyperactivity disorder

Abstract

Attention deficit hyperactivity disorder (ADHD) is a complex genetic disorder that is caused by multiple heritable and environmental factors. Serotonergic system-related genes are likely to be involved in the mechanisms underlying ADHD, because serotonin dysregulation has been related to impulsive and aggressive behavior in children, and has thus been hypothesized to play a causal role in ADHD. The firing rate of the dorsal raphe serotonergic neurons is modulated by somatodendritic 5-hydroxytryptamine 1A (5-HT1A) autoreceptors. The human 5-HT1A receptor gene (HTR1A) transcription is modulated by a functional C-1019G promoter polymorphism (rs6295). In a case–control association study with 78 Korean ADHD patients and 107 normal controls, Shim et al. (2010) found a significant difference in the genotype distributions and allele frequencies of HTR1A C-1019G between the ADHD group and the control group (P = 0.044 and 0.017, respectively). Tryptophan hydroxylase 2 (TPH2) is a rate-limiting enzyme in the biosynthesis of serotonin and is expressed exclusively in the brain. In 103 German families with 225 ADHD children, Walitza et al. (2005) reported a preferential transmission for two polymorphisms in TPH2’s regulatory region (rs4570625, P = 0.049; rs11178997, P = 0.034).