Catechol-O-methyltransferase Val108/158Met genotype predicts working memory response to antipsychotic medications

Background: The gene encoding catechol-O-methyltransferase (COMT), an enzyme that regulates prefrontal cortex dopamine, contains a common functional polymorphism (val(108/158)met) that influences prefrontal cortex function in an allelic dose-dependant manner. A recent study reported that the COMT val(108/158)met polymorphism influences cognitive- and physiologic-related prefrontal cortex response to antipsychotic treatment. The present study tested the effects of several COMT polymorphisms on the cognitive response to antipsychotic medication in patients with schizophrenia. Methods: Twenty inpatients with schizophrenia or schizoaffective disorder (5 with the val-val genotype, 11 with val-met, and 4 with met-met) were administered cognitive tests at two time points: once after 4 weeks of treatment with antipsychotic medication and once after 4 weeks of placebo administration, according to a counterbalanced, double-blind, within-subject study design. Results: Patients homozygous for the COMT met allele displayed significant improvement on the working memory task after treatment. Patients homozygous for the COMT val allele did not show working memory improvement with treatment. Other COMT polymorphisms were not associated with significant differences between treatment and placebo conditions. Conclusions: These results support other data suggesting that the COMT val(108/158)met polymorphism might be an important factor in the cognitive response to antipsychotic medication.