Low activity allele of catechol-O-methyltransferase gene associated with rapid cycling bipolar disorder

Mol Psychiatry. 1998 Jul;3(4):342-5. doi: 10.1038/sj.mp.4000385.


Catechol-O-methyltransferase (COMT) plays a major role in the breakdown of catecholamines. An amino acid polymorphism (val-108-met) determines high and low activity of the enzyme. A recent study in a small sample of patients with velo-cardio-facial syndrome who had bipolar affective disorder suggested that the Met (low activity) COMT allele might be associated with rapid-cycling in this population. We therefore tested the hypothesis that the Met allele might be associated with 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 alleles showed a dose-dependent increased risk of lifetime occurrence of rapid 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Substitution
  • Bipolar Disorder / enzymology
  • Bipolar Disorder / epidemiology
  • Bipolar Disorder / genetics*
  • Bipolar Disorder / psychology
  • Catechol O-Methyltransferase / genetics*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Point Mutation
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Risk Assessment
  • United Kingdom
  • White People


  • Catechol O-Methyltransferase