Abstract
Schizophrenia (SZ) is a debilitating disease that impacts 1% of the population worldwide. Association studies have shown that inherited genetic mutations account for a portion of disease risk. However, environmental factors play an important role in the pathophysiology of the disease by altering cellular epigenetic marks at the level of chromatin. Postmortem brain studies of SZ subjects suggest that the dynamic equilibrium between DNA methylation and demethylation network components is disrupted at the level of individual SZ target genes. Herein, we review the role of DNA methylation and demethylation in the context of what is currently known regarding SZ. Furthermore, we describe the deficits that accompany two mouse models of SZ. The chronic methionine mouse model of SZ is predicated on the administration of methionine to SZ patients and controls in the context of clinical studies that were carried out during the 1960s and 1970s. The prenatal restraint stress model of SZ is based on a prolonged stress paradigm administered to pregnant dams during gestation days 7-21. The adult offspring of these dams show various behavioral and biochemical deficits in adulthood. Both models are epigenetic in origin and mimic the positive and negative symptoms, as well as the cognitive endophenotypes commonly observed in SZ patients. We also discuss the utility of typical and atypical antipsychotic drugs in alleviating these symptoms in each model.