Epigenomics of Psychiatric Disease


Campbell Family Mental Health Research Institute Centre for Addiction and Mental Health, Toronto, Canada
University of Toronto, Toronto, Canada


Putative epigenetic misregulation of genes sheds a new light on numerous epidemiological, clinical, and molecular complexities of psychiatric and other common human diseases. Perfect DNA sequences may be useless or even harmful if not expressed in the appropriate amount, at the right time of the cell cycle, or in the right compartment of the nucleus. Epigenetic modifications of DNA and histones, more so than DNA sequence-based ones, can explain a series of general non-Mendelian features of major psychiatric disease: discordance of identical twins; relatively late age of onset and coincidence of the first symptoms with changes in the hormonal status in the organism; sexual dimorphism; parental origin effects; fluctuating course and sometimes partial or even full recovery. Apart from the general epigenetic aspects of non-Mendelian irregularities, epigenetic mechanisms may also provide a new perspective on the neurochemical and neurodevelopmental findings as well as identification of the molecular effects of environmental and stochastic factors. The epigenetic theory does not reject the role of DNA sequence variation but rather suggests that in complex psychiatric diseases the contribution of epigenetic factors may be substantial, and that DNA sequence variation should be investigated in parallel with epigenetic regulation. I will discuss the key theoretical principles of psychiatric epigenomics and review recent experimental activities dedicated to identification of inherited and acquired epigenetic changes in common psychiatric diseases.