Does COMT val¹⁵⁸met affect behavioral phenotypes: Yes, no, maybe?

The COMT gene functional polymorphism val¹⁵⁸met is one of the most intensively studied variants in psychiatric genetics. Due to small effect size and various methodological issues, its role in various psychiatric disorders and behavioral traits has still not been unequivocally established. In this issue of Neuropsychopharmacology, several studies are presented supporting a role for COMT as a factor in cocaine addiction, brain reward activation, response to tolcapone, distractibility in ADHD, and fMRI bold response. The studies make important contributions to the growing literature that aim to establish an effect of this functional variant on behavioral phenotypes and treatment response.