Transmission disequilibrium analysis of the functional 5-HT3A receptor variant C178T in early-onset obsessive...

The 5-HT(3) 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-HT(3) receptor antagonist has recently been shown to benefit some OCD patients, suggesting the 5-HT(3) 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.