Catechol-O-methyltransferase val108/158met genotype and response to antipsychotic medication in schizophrenia Ari Illi 1,4 * , Olli Kampman 1,5 , Kari Ha ¨nninen 6 , Sami Anttila 1 , Kari M. Mattila 3 , Heikki Katila 7 , Riikka Rontu 3 , Mikko Hurme 1 , Terho Lehtima ¨ki 3 and Esa Leinonen 1,2 1 University of Tampere, Medical School, Tampere, Finland 2 Tampere University Hospital, Department of Psychiatry, Tampere, Finland 3 Laboratory of Atherosclerosis Genetics, Centre for Laboratory Medicine, Tampere University Hospital and Department of Clinical Chemistry, University of Tampere, Medical School, Tampere, Finland 4 Kanta-Ha ¨me Central Hospital, Department of Psychiatry, Ha ¨meenlinna, Finland 5 Seina ¨joki Hospital District, Department of Psychiatry, Seina ¨joki, Finland 6 South Karelia Central Hospital, Department of Psychiatry, 53130 Lappeenranta, Finland 7 Helsinki University Central Hospital, Department of Psychiatry, 00180 Helsinki, Finland Catechol-O-methyltransferase (COMT) gene has been investigated as a possible candidate gene in schizophrenia. The most studied polymorphism has been the functional val108/158met polymorphism of this COMT gene. There is also some evidence that this polymorphism could be related to drug response to antipsychotics in schizophrenia. COMT enzyme inactivates dopamine and noradrenaline. Based mainly on the original dopamine theory of schizophrenia, our primary hypothesis was that the maintenance dose of antipsychotics would be higher in patients with the low activity COMT genotype. In this study we evaluated the current daily dosage of antipsychotics in 180 patients with schizophrenia in connection with the COMT genotype. We could not demonstrate any clearly significant effect of this particular COMT genotype in relation to the daily maintenance dosages of antipsychotics in patients with schizophrenia. Copyright # 2007 John Wiley & Sons, Ltd. key words — COMT; schizophrenia; drug response; antipsychotic agents; polymorphism INTRODUCTION Catechol-O-methyltransferase (COMT) gene has been investigated intensively as a possible candidate gene in schizophrenia. The role of COMT gene in the pathogenesis of schizophrenia is not finally clarified even though it is theoretically very interesting. The most studied polymorphism of COMT gene has been the functional polymorphism (val108/158met) of the COMT gene. This polymorphism is due to a G to A transition at codon 158 of the membrane bound form of COMT, which corresponds to codon 108 of the soluble form of COMT, resulting in a valine (val) to methionine (met) substitution (Lotta et al., 1995; Lachman et al., 1996). COMT enzyme participates in the metabolic inactivation of dopamine and nor- adrenaline. The activity of COMT is governed by this common polymorphism that results in substantial 3-4-fold variations in enzymatic activity (Weinshil- boum and Raymond, 1977; Spielman and Weinshil- boum, 1981). The low activity COMT genotype (COMTmet/met) consisting of a met/met allele pair results in 3-4 fold lower enzyme activity compared to the high activity genotype (COMTval/val) having a val/val allele pair; the COMTmet/val genotype causing intermediate enzyme activity. The results of the studies evaluating the possible role of this common polymorphism in schizophrenia have been contradictory. There have been several conflicting reports of associations (Daniels et al., 1996; Strous et al., 1997; Karayiorgou et al., 1998; Ohmori et al., 1998; Lachman et al., 1998; Kotler human psychopharmacology Hum. Psychopharmacol Clin Exp 2007; 22: 211–215. Published online in Wiley InterScience (www.interscience.wiley.com) DOI: 10.1002/hup.841 *Correspondence to: Dr A. Illi, University of Tampere, Medical School, FIN-33014 Tampere (University), Finland. Tel: þ358-3-2156737. Fax: þ358-3-35516164. E-mail: ari.illi@uta.fi Copyright # 2007 John Wiley & Sons, Ltd. Received 17 November 2006 Accepted 28 February 2007