1. ¹Clarke Division, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada
2. ²Department of Psychiatry, University of Münster, Münster, Germany
3. ³Department of Psychiatry, University of Ottawa and the University of Ottawa Institute of Mental Health Research, Royal Ottawa Hospital, Ottawa, ON, Canada

Correspondence: Dr JL Kennedy, Department of Psychiatry and Institute of Medical Science, Centre for Addiction and Mental Health, University of Toronto, 250 College Street, Toronto, ON, Canada M5T 1R8, Tel: +1 416 979 4987, Fax: +1 416 979 4666, E-mail: James_Kennedy@camh.net

Received 9 March 2005; Revised 14 December 2005; Accepted 24 December 2005; Published online 8 March 2006.

Abstract

Genetic as well as clinical data suggest that catechol O-methyltransferase (COMT) is involved in multiple complex psychiatric conditions. Recent studies have described an association between the Val158Met COMT polymorphism and panic disorder. Other recent investigations provide evidence that there are other loci within or nearby the COMT gene that may contribute to the susceptibility to panic disorder. To further evaluate the influence of the Val158Met COMT polymorphism in panic disorder we genotyped this marker in the coding region of the COMT gene and two additional variants (rs737865 and rs165599) in the 5' and the 3' region, respectively, in two independent Canadian samples: 121 nuclear families, and 89 cases with matched controls. In the nuclear families, significant transmission disequilibrium for the valine allele was observed between the alleles of the Val158Met COMT polymorphism and panic disorder (p<0.01). A significant excess of the valine allele was found in analysis of the case–control sample (p<0.01). This effect was mainly derived from the subgroup of females. This finding, including the female effect, replicates earlier results in studies of the Val158Met polymorphism in panic disorder. No significant results were found for the other two markers. These results support the hypothesis that the valine allele of the Val158Met COMT polymorphism or a nearby locus is involved in the etiopathogenesis of panic disorder.