Transmission disequilibrium analysis of the functional 5-HT 3A receptor variant C178T in early-onset obsessive—compulsive disorder

Abstract

The 5-HT₃ receptor is unique among the serotonin receptors in that it is a ligand-gated ion channel. Dysfunction of the serotonin system is thought to contribute to the pathogenesis of obsessive—compulsive disorder (OCD). Apart from the standard treatment with serotonin reuptake inhibitors and behavioural therapy, a 5-HT₃ receptor antagonist has recently been shown to benefit some OCD patients, suggesting the 5-HT₃ receptor as a serotonergic candidate gene in the polygenic aetiology of OCD. A functional regulatory variant of the 5-HT_3A receptor influences 5-HT ₃ receptor expression, serotonin metabolites in cerebrospinal fluid, and amygdala reactivity. We therefore assessed whether this C178T variant influences the risk of developing OCD. In a family-based approach employing the transmission disequilibrium test, we analysed a unique sample of 75 children and adolescents with OCD, as well as their biological parents. We found no evidence for a preferential transmission of either allele to the patients — the estimated transmission rate for the C allele was 0.51 (95% CI 0.36—0.65). This argues against an involvement of the 5-HT_3A receptor in the polygenic aetiology of early-onset OCD.