Head-to-head comparison of various antipsychotic agents on genome-wide methylation in schizophrenia.

Aim: To explore possible differences in genome-wide methylation between schizophrenia patients who consume various antipsychotics. Methods: We compared DNA methylation in leukocytes between the following cohorts: clozapine (n = 19) versus risperidone (n = 19), clozapine (n = 12) versus olanzapine (n = 12), clozapine (n = 9) versus quetiapine (n = 9) and clozapine (n = 33) versus healthy controls (n = 33). Subjects were matched for age, sex, ethnicity, smoking status and leukocyte proportions. Results: No single CpG site reached genome-wide significance for clozapine versus risperidone/olanzapine/quetiapine. For clozapine versus quetiapine, one significantly differentially methylated region was found - ch5: 176797920-176798049 (fwer = 0.075). Clozapine versus healthy controls yielded thousands of significantly differentially methylated CpG sites. Conclusions: Establishing antipsychotic induced genome-wide methylation patterns will further elucidate the biological and clinical effects of antipsychotic administration.