Epigenetic Signaling in Psychiatric Disorders

Abstract

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 is revealing new insight into disease mechanisms in humans.

Dynamics of epigenetic phenomena: intergenerational and intragenerational phenotype ‘washout’

“…Sometimes -but not always -these phenotypic changes involved transgenerational phenotype transfer. An extensive literature now exists in medicine, where epigenetics is viewed in a pathological light (Jones and Sung, 2014;Mazzio and Soliman, 2014;Mill and Heijmans, 2013;Ogino et al, 2013); in biology, where epigenetics is of interest from an adaptive or evolutionary vantage rather than as a pathology (Burggren, 2014;Burggren and Crews, 2014;Cropley et al, 2012;Horowitz, 2014;Kuzawa and Thayer, 2011;Varriale, 2014); and in the psychological-behavioral field (Crews, 2008;Peña et al, 2014;Pishva et al, 2014;Rutten and Mill, 2009;Svrakic and Cloninger, 2010). Noteworthy is that, in recent years, terminology surrounding epigenetics has been rendered more complex by the increasingly common practice in medicine to refer to epigenetics as an intragenerational phenomenon that creates pathologies during an individual's lifetime -e.g.…”

The role of chromatin repressive marks in cognition and disease: A focus on the repressive complex GLP/G9a

“…Many of these disorders involve, among others, memory impairment, learning deficits and neurodevelopmental delays (Barco, 2014;Kelly, De Carvalho, & Jones, 2010;Kleefstra et al, 2014;Peña, Bagot, Labonté, & Nestler, 2014;Portela & Esteller, 2010). Intellectual disability (ID) is a common neurodevelopmental disorder arising before the age of 18 that affects approximately 1-3% of the population.…”

Neurogenetic and Epigenetic Correlates of Adolescent Predisposition to and Risk for Addictive Behaviors as a Function of Prefrontal Cortex Dysregulation

“…It is well known that epigenetic factors affect subsequent infant behaviors; extrapolation from many animal studies indicates that a take-away message ''lick your pups'' could have really important meaning even in terms of human interaction, and in shaping adolescent behavior (Pena et al 2014). This concept is underscored by work from Hao et al (2011), showing that rodent dams lick male pups more than they lick female pups in the anogenital and other regions of the body.…”