Epigenetic Dysregulation in the Schizophrenic Brain

Schizophrenia (SCZ) is a severe psychiatric disorder, which lacks a unifying neuropathology. However, reproducible molecular alterations exist, including RNA expression changes affecting GABAergic and other neuronal signaling in cerebral cortex, myelination, and other cellular functions. Yet, for the large majority of RNAs altered in the SCZ brain, the underlying transcriptional and post-transcriptional disease-associated mechanisms remain unclear. Here, we provide an update on epigenetic regulators of gene expression that are potentially affected in some cases with SCZ, including DNA cytosine methylation, histone modifications and histone variants, and chromosomal loop formations facilitating long-range interactions of gene promoters with distal enhancer elements. Exploration of chromatin structure and function, in combination with transcriptome and genome sequencing, is likely to critically advance insight into the molecular mechanisms of disease in specific cases with SCZ.