Recurrence of bipolar mania is associated with catechol-O-methyltransferase Val(108/158)Met polymorphism

Background: Catechol-O-methyltransferase (COMT) inactivates catecholamines, and a G-A transition in the COMT gene (rs4680) influences the enzyme activity and the interaction between cortical and subcortical dopaminergic neurotransmission. In patients affected by bipolar disorder rs4680 can influence antidepressant response and the propensity to develop psychotic symptoms, with the Met/Met genotype exerting a protective role. The same genotype could influence other dopamine-associated psychopathological features, such as mania. Methods: We genotyped rs4680 in a sample of 163 patients affected by bipolar disorder type I, and assessed the personal history of recurrence of the illness. Results: We observed a significant association between homozygosis for the rs4680 COMT low-activity variant and a reduced recurrence of manic, but not depressive, episodes during the course of the illness. Conclusions: We suggest that rs4680 could be an inheritable aspect of the mechanisms of dopamine regulation that influence the individual susceptibility of patients with bipolar disorder to develop manic episodes of illness.