Epigenetic Signaling in Psychiatric Disorders

Psychiatric disorders are complex multifactorial illnesses involving chronic alterations in neural circuit structure and function. While genetic factors are important in the etiology of disorders such as depression and addiction, relatively high rates of discordance among identical twins clearly indicate the importance of additional mechanisms. Environmental factors such as stress or prior drug exposure are known to play a role in the onset of these illnesses. Such exposure to environmental insults induces stable changes in gene expression, neural circuit function, and ultimately behavior, and these maladaptations appear distinct between developmental and adult exposures. Increasing evidence indicates that these sustained abnormalities are maintained by epigenetic modifications in specific brain regions. Indeed, transcriptional dysregulation and associated aberrant epigenetic regulation is a unifying theme in psychiatric disorders. Aspects of depression and addiction can be modeled in animals by inducing disease-like states through environmental manipulations (e.g., chronic stress, drug administration). Understanding how environmental factors recruit the epigenetic machinery in animal models reveals new insight into disease mechanisms in humans. Epigenetic mechanisms of gene regulation in hypothalamic-pituitary-adrenal axis (left) and reward (right) circuitry are modulated by stress and drug exposure and appear to underlie psychiatric disorders such as depression and addiction. [Display omitted] •Discussion of current evidence for epigenetic dysregulation in depression and addiction.•Insights from both animal and human studies.•Special focus on findings from developmental versus adult studies.