Olanzapine-induced DNA methylation in the hippocampus and cerebellum in genes mapped to human 22q11 and implicated in schizophrenia

Background: Although there is indirect evidence that the effects of antipsychotic drugs may involve modulation of dopamine transmission, their mechanism of action is poorly understood. We hypothesized that antipsychotic drugs mediate their effects by epigenetic modulation. Here, we tested the effect of an antipsychotic, olanzapine, on the DNA methylation status of genes following chronic treatment using rat-specific methylation arrays. Methods: Forty-eight hours after the last dose of olanzapine/vehicle, rats were habituated to an open-field activity-monitoring chamber for 30 min to verify whether stress-induced locomotor activity was reduced in olanzapine-treated rats. To test this hypothesis, we examined the effect of olanzapine, a commonly used atypical antipsychotic drug, on the DNA methylation status of 49 genes mapped to human 22q11 and implicated in schizophrenia. Genomic DNA isolated from the cerebellum, hippocampus, and liver of olanzapine-treated (n=2) and control (n=2) rats were analyzed using rat-specific methylation arrays. Results: Significantly reduced locomotor activity of olanzapine-treated rats confirmed the therapeutic efficacy of the drug administered. The effects of olanzapine have been shown through significantly increased (P
Source: Psychiatric Genetics - Category: Genetics & Stem Cells Tags: Original Articles Source Type: research