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

Kirov, George ORCID:, Murphy, K. C., Arranz, M. J., Jones, Ian Richard ORCID:, McCandless, F., Kunugi, H., Murray, R. M., McGuffin, P., Collier, D. A., Owen, Michael John ORCID: and Craddock, Nicholas John ORCID: 1998. Low activity allele of catechol-O-methyltransferase gene associated with rapid cycling bipolar disorder. Molecular Psychiatry 3 (4) , pp. 342-345. 10.1038/

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: R Medicine > R Medicine (General)
R Medicine > RZ Other systems of medicine
Publisher: Nature Publishing Group
ISSN: 1359-4184
Last Modified: 27 Oct 2022 08:43

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