Epigenetic Alterations in Schizophrenia

The inheritance pattern of schizophrenia is complex, with increased rates of illness observed among the first- and second-degree relatives of affected individuals but only about 60% concordance among monozygotic twins. This pattern has been interpreted as indicating that multiple genes and environmental influences may be involved (i.e., “multifactorial” inheritance). Additional epidemiological data, including age of onset in adolescence and young adulthood, varying age of onset between males and females, association between advancing paternal age and risk to offspring, and association with in utero nutritional deficiency, viral exposure, and hypoxia, also suggest that “epigenetic” factors may be important. Epigenetics broadly refers to heritable changes in phenotype or gene expression caused by mechanisms other than changes in the underlying primary DNA sequence. In this review, several major types of epigenetic mechanisms are described, including DNA methylation, genomic imprinting, histone modifications, and expression control by noncoding RNA. Recent data suggesting the influence of these epigenetic alterations in schizophrenia are presented.