Selective role for the COMT polymorphism in a trans-diagnostic compulsivity phenotype.

BACKGROUND: Impulsivity and compulsivity are central to understanding a range of psychiatric disorders but also to understanding the spectrum of normative human behavior. It was recently shown that separable latent phenotypes of impulsivity and compulsivity could be fractionated. The possible genetic contributions to these latent phenotypes have yet to be elicited. The catechol-o-methyl transferase (COMT) Val158Met polymorphism (rs4680) regulates cortical dopamine degradation and is a key area of interest in this context. METHODS: COMT Val158Met polymorphism status was obtained from a random subset (n = 258) of young adults from an established cohort, for whom latent phenotype scores were previously reported. Differences in latent phenotype scores were explored between COMT groups using analysis of variance (ANOVA) and post-hoc t tests. RESULTS: The Val-Val subgroup exhibited significantly elevated compulsivity scores compared to both other groups. Impulsivity scores did not differ significantly as a function of COMT Val158Met polymorphism status. CONCLUSIONS: These results suggest that the COMT polymorphism, and by implication cortical dopamine degradation, influences the expression of a trans-diagnostic compulsivity phenotype, even accounting for possible confounding effects of impulsivity.Wellcome Trus