title: Catechol-O-methyltransferase and monoamine oxidase A genotypes and drug response to conventional neuroleptics in schizophrenia.
abstract: Biogenic amine synthesis and degradation are involved in the pathogenesis of schizophrenia. Catechol-O-methyltransferase and monoamine oxidase enzymes are important agents in the metabolic inactivation of these neurotransmitters (ie, dopamine, serotonin, and norepinephrine). Functional polymorphism in the catechol-O-methyltransferase and monoamine oxidase A genes causes variation in enzyme activities. We investigated the relationship of catechol-O-methyltransferase Val158Met and monoamine oxidase A promoter repeat polymorphism with response to conventional neuroleptic treatment in schizophrenia.Ninety-four schizophrenic patients formed 2 different study populations. The responders had experienced a fair and steady response to conventional neuroleptics. The nonresponders had failed to achieve an acceptable response to conventional neuroleptics. We also used a control population of 94 age-matched and gender-matched blood donors. Genotyping of the catechol-O-methyltransferase and monoamine oxidase A genes was performed by polymerase chain reaction.Forty-three percent of the nonresponders had a low activity catechol-O-methyltransferase genotype compared with 16% of the responders (P = 0.009). Monoamine oxidase A genotype alone did not differ significantly between the groups. Moreover, the risk of having both low-activity catechol-O-methyltransferase and monoamine oxidase A genotypes was over 6 times more common (odds ratio = 6.16, P = 0.03) in the nonresponders compared with responders. The whole population of patients with schizophrenia did not differ from the controls.The low-activity catechol-O-methyltransferase genotype may be associated with unsatisfactory drug response to conventional neuroleptics or alternatively be involved in a subset of schizophrenics. The role of monoamine oxidase A genotype seems to be additive in this respect.
authors.affiliation: Department of Psychiatry, Tampere University Hospital, Tampere, Finland. ari.illi@uta.fi
authors.forename: Ari
authors.initials: A
authors.lastname: Illi
authors.forename: Kari M
authors.initials: KM
authors.lastname: Mattila
authors.forename: Olli
authors.initials: O
authors.lastname: Kampman
authors.forename: Sami
authors.initials: S
authors.lastname: Anttila
authors.forename: Markus
authors.initials: M
authors.lastname: Roivas
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
authors.forename: Esa
authors.initials: E
authors.lastname: Leinonen
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D016009:Chi-Square Distribution; D005260:Female; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000235:genetics*; D016017:Odds Ratio; D012559:Schizophrenia / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics*
chemical_list: D014150:Antipsychotic Agents; D008995:Monoamine Oxidase; D002394:Catechol O-Methyltransferase