Epigenetic Epidemiology of Psychiatric Disorders

Abstract

Exciting developments in the field of epigenetics have generated great interest within psychiatric epidemiology to focus on direct and indirect evidence for epigenetic involvement in behavior, mental health, and complex psychiatric disorders. Epidemiologic evidence on epigenetics in psychiatry, however, is currently very sparsely available. With the aim to address the current status of the literature on evidence indicative of involvement of epigenetic mechanisms in psychiatric disorders, we describe a clear role for epigenetic mechanisms in development and aging of the brain, with experiences and environmental exposures particularly during early life having considerable impact on the development of functional abilities of the brain. Besides the psychiatric consequences of classical syndromes of genetic imprinting in humans, findings of twin discordance, parent-of-origin effects, paternal age effects, and sex differences in psychiatric disorders suggest epigenetic involvement in the etiology of psychiatric disorders. The evidence is further strengthened by observations of endurable effects of various environmental exposures during life on risk of psychiatric disorders, and preliminary epigenetic studies showing differential epigenetic profiles in patients with several psychiatric disorders. Findings of these first (and preliminary) epigenetic studies should be interpreted with caution because of small samples sizes, lack of replication, limitations in the etiologic validity of psychiatric diagnoses, and in accessibility of the regions and cell types of the brain at “appropriate” periods during life. Despite the sparse availability, the current evidence for epigenetic involvement in (particularly early) brain development, mental health, and psychiatric disorders appears very promising, and may be used in bringing together inherited and acquired risk factors into a neurodevelopmental etiological model of psychiatric disorders with epigenetics as a plausible key mediating mechanism. Given the dynamic nature of epigenetic regulation of gene expression and the potential reversibility of epigenetic modifications, future well-designed multidisciplinary and translational studies will be of key importance in order to identify new targets for prevention and therapeutic strategies.