COMT (Val(158/108)Met) genotype moderates the impact of antipsychotic medication on verbal IQ in twins with schizophrenia.

OBJECTIVES In this study, we aimed to assess the moderating effects of the catechol-O-methyl transferase (COMT) (Val(158/108)Met) genotype on antipsychotic medication-induced changes in the cognitive performance of patients with chronic schizophrenia. METHODS The sample consisted of 85 monozygotic and 53 dizygotic twin pairs, of varying concordance for schizophrenia, and healthy control twins. Cognitive ability was measured using the Wechsler Adult Intelligence Scale-third edition. We used structural equation modelling to estimate main and interaction effects of the COMT status and antipsychotic medication dose on verbal intelligence quotient (VIQ) and performance intelligence quotient scores. RESULTS There was no evidence of a main or interaction effect of the COMT status or chlorpromazine equivalent dose on the performance intelligence quotient. There were no main effects of COMT or chlorpromazine equivalent dose on VIQ; however, there was evidence of a statistically significant interaction (P<0.01) between the COMT and chlorpromazine equivalents on VIQ. The VIQ performance of val/val individuals was significantly lower with increasing antipsychotic medication dose, up to 12 intelligence quotient points lower than met carriers treated with medication. In the absence of medication, the three genotypes did not significantly differ, whereas at the highest doses (1500), the val/val homozygotes and Met carriers differed by more than one standard deviation. CONCLUSION Our results show that the verbal abilities of val homozygotes of the COMT gene are cognitively impaired by higher doses of antipsychotic medication. This association is reversed in Met carriers. These data are consistent with an earlier study that found evidence of moderating effects of antipsychotic medication on N-back and verbal fluency tasks.