Chapter One - Neuroepigenetics of Mental Illness: The Inside Outs of the Outside Within

Epigenetics refers to environmentally sensitive modifications to DNA and chromatin that regulate gene transcription without altering the genetic sequence itself. Because of the brain's central role in a person's adaptation to dynamic changes in the environment, the field of epigenetic research is particularly pertinent for the neurosciences and mental health and illness. "Neuroepigenetics" refers to the field of epigenetics, as applied to research of the nervous system and related functional abilities. The onset and course of mental disorders revolve around person-environment interactions, i.e., the interplay between environmental factors with people (and their brain) throughout life and on the background of an individual's inherited genomic make-up. With respect to the nervous system and its functional abilities, neuroepigenetic research aims to turn the inside outs by explicating the epigenetic profiles that regulate gene expression within cells while epigenetic profiles themselves may reflect the imprints of external factors (the outside of the organism). Neuroepigenetic research is of prime importance for elucidating the molecular underpinnings of gene-environment interplay in relation to functional abilities of the brain and mental health throughout life, and thus for identifying the mechanisms underlying onset and course of mental disorders. However, neuroepigenetic research is still in its infancy and many conceptual and methodological challenges are apparent. In addition, there are considerable complexities and major challenges in conceptualizing the nature and diagnosis of mental disorders, and these need to be taken into account in studying neuroepigenetics of mental disorders. The current manuscript provides an overview and conceptual framework for neuroepigenetic research in mental disorders.