ORIGINAL ARTICLE Catechol-O-methyltransferase (COMT) polymorphisms predict treatment response in electroconvulsive therapy Sami Anttila 1,2 , Kaija Huuhka 1,3 , Martti Huuhka 1,3 , Ari Illi 1,4 , Riikka Rontu 1,2 , Esa Leinonen 1,3 and Terho Lehtima ¨ki 1,2 1 University of Tampere Medical School, University of Tampere, Tampere, Finland; 2 Department of Clinical Chemistry, Laboratory of Atherosclerosis Genetics, Centre for Laboratory Medicine, Tampere University Hospital, Tampere, Finland; 3 Department of Psychiatry, Tampere University Hospital, Pitka ¨niemi, Finland and 4 Department of Psychiatry, Kanta-Ha ¨me Central Hospital, Ha ¨meenlinna, Finland Correspondence: Dr S Anttila, Department of Psychiatry, Tampere University Hospital, Pitka ¨niemi 33380, Finland. E-mail: samia@koti.soon.fi Received 18 February 2007; revised 9 May 2007; accepted 4 June 2007; published online 14 August 2007 Several lines of evidence suggest that catechol-O-methyltransferase (COMT) may be associated with treatment response in depression. We conducted a study on 119 patients with treatment-refractory depression admitted consecutively for electroconvulsive therapy (ECT). The COMT high/high genotype leads to a higher enzyme activity and thus lowers dopaminergic activity in the prefrontal cortex. In the present sample, those homozygous to high-active allele of COMT responded significantly more frequently to ECT. The Pharmacogenomics Journal (2008) 8, 113–116; doi:10.1038/sj.tpj.6500468; published online 14 August 2007 Keywords: COMT; polymorphism; major depression; electroconvulsive therapy; ECT Introduction Electroconvulsive therapy (ECT) is the most effective treatment in major depression. 1,2 However, the mechanism of the action of ECT is unknown. Several lines of evidence suggest that dopaminergic actions in the prefrontal cortex may be involved. 2–8 Catechol-O-methyltransferase (COMT) is a major enzyme in dopamine metabolism in the prefrontal cortex. A common functional polymorphism at codon 158 in the gene coding for COMT (COMT Val158Met) results in substantial effects, with Met (low-activity) allele homozygosity leading to a three- to fourfold reduction in enzymatic activity compared with the Val (high- activity) allele homozygosity. 9 Given that ECT has been shown to affect the dopaminergic functions of the prefrontal cortex, COMT is a suitable candidate gene for a pharmacogenetic study. As COMT significantly affects the dopaminergic activity in prefrontal cortex, we hypothesized that COMT polymorphism may be associated with treatment response in ECT. Results Patients who had o8 scores in Montgomery and A ˚ sberg Depression Rating Scale (MADRS) 1 were considered responders (n ¼ 45). Scores 415 in MADRS1 indicated nonresponse (n ¼ 32). COMT high/high genotype carriers were more often responders than nonresponders: odds ratio (OR) ¼ 4.366 (95% confidence interval (CI) 1.137–16.770; P ¼ 0.023) (Table 1). Before ECT treatment, MADRS0 scores were not associated with COMT polymorphisms (P40.22, analysis of variance (ANOVA)) (Table 1). The Pharmacogenomics Journal (2008) 8, 113–116 & 2008 Nature Publishing Group All rights reserved 1470-269X/08 $30.00 www.nature.com/tpj