LOW ACTIVITY ALLELE OF CATECHOL-O-METHYLTRANSFERASE GENE ASSOCIATED WITH RAPID-CYCLING BIPOLAR DISORDER

Catechol-O-methyltransferase (COMT) plays a major role in the breakdow n of catecholamines.(1) An amino acid polymorphism (val-108-met) deter mines high and low activity of the enzyme.(2,3) A recent study in a sm all sample of patients with velo-cardio-facial syndrome who had bipola r affective disorder suggested that the Met (low activity) COMT allele might be associated with rapid-cycling in this population.(4) We ther efore tested the hypothesis that the Met allele might be associated wi th rapid cycling bipolar disorder in the wider population. We studied a sample of British Caucasian DSM-IV bipolar patients, of whom 55 met criteria for rapid cycling at some time during the illness and 110 met stringent criteria for a definite non-rapid cycling course. The COMT genotype was determined using a PCR assay. The low activity allele was more frequent in the group of rapid cyclers: 0.55 vs 0.42 (one-tailed chi(2) = 5.12, d.f. = 1, P = 0.012), and bearers of low activity alle les showed a dose-dependent increased risk of lifetime occurrence of r apid cycling: chi(2) test of linear association = 4.84, d.f. = 1, P = 0.014. Our data support the hypothesis that variation in the COMT gene modifies the course of bipolar disorder.