Epigenetics of Brain Disorders

Abstract

Epigenetic mechanisms are essential for the development and maintenance of neuronal networks, and for higher-order brain processes such as cognitive functions and behavior. Defects in epigenetic mechanisms increase disease susceptibility, contribute to the etiology and pathophysiology of disorders, and influence the response to therapy. Epigenetic dysfunctions have been implicated in neurodevelopmental disorders, neurodegenerative and psychiatric conditions, and even in transgenerational effects of the environment on brain and body functions. This chapter describes epigenetic processes in the brain ranging from DNA and histone modifications to non-coding RNA. Aspects of epigenetic (dys-)regulation in neurodevelopmental and neurodegenerative disorders are discussed using the examples of Rett syndrome and Alzheimer disease, and epigenetic mechanisms associated with the development of depression, and their relation to the effects of antidepressant treatments are described. We also discuss recent work on the epigenetic contribution to transgenerational effects, and provide an overview of how early-life trauma can induce epigenetic changes that influence brain functions in the adult, and how these effects can be transmitted across generations. The chapter concludes with a representative case study that illustrates the translational relevance of the described epigenetic processes in human brain health and disease.