Epigenetics Mechanisms

Epigenetic Mechanism

Histone acetylation and the expression of histone modifying enzymes in the hippocampus, medial prefrontal cortex and dorsal raphe nucleus have also been found to correlate with behavioral outcomes associated with chronic social defeat stress (Kenworthy et al., 2013). Of course this form of stress can also have long-term effects on regulation of the hypothalamic-pituitary-adrenal (HPA) axis, and other groups have provided evidence that additional genes associated with HPA regulation are epigenetically modified by stress. Susceptible mice, or mice that spend less time in a social interaction zone after social defeat, have been found to display long-lived demethylation of hypothalamic corticotrophin releasing factor (CRF) gene, which produces an overactive HPA axis and social avoidance behaviors (Elliott, Ezra-Nevo, Regev, Neufeld-Cohen, & Chen, 2010). Resilient mice instead spend more time in the social interaction zone after defeat and do not display the same epigenetic changes.

Dev Psychopathol. Author manuscript; available in PMC 2016 May 1.

Published in final edited form as:

Dev Psychopathol. 2015 May; 27(2): 637–648.

doi:  10.1017/S0954579415000206

PMCID: PMC4489549


Epigenetic pathways through which experiences become linked with biology

Patrick O. McGowan1 and Tania L. Roth2

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The publisher’s final edited version of this article is available at Dev Psychopathol

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This article highlights the defining principles, progress, and future directions in epigenetics research in relation to this special issue. Exciting studies in the fields of neuroscience, psychology, and psychiatry have provided new insights into the epigenetic factors (e.g. DNA methylation) that are responsive to environmental input and serve as biological pathways in behavioral development. Here we highlight the experimental evidence, mainly from animal models, that factors such as psychosocial stress and environmental adversity can become encoded within epigenetic factors with functional consequences for brain plasticity and behavior. We also highlight evidence that epigenetic marking of genes in one generation can have consequences for future generations (i.e. inherited), and work with humans linking epigenetics, cognitive dysfunction, and psychiatric disorder. Though epigenetics has offered more of a beginning than an answer to the centuries-old nature-nurture debate, continued research is certain to yield substantial information regarding biological determinants of CNS changes and behavior with relevance for the study of developmental psychopathology.

Keywords: DNA methylation, plasticity, memory, sensitive periods, transgenerational inheritance, stress

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Experiences, particularly those occurring during sensitive periods of development, are well-recognized for their ability to canalize neurobiological trajectories and yield significant consequences for life-long health and mental well-being. For some time now it has also been recognized that proper brain development and life-long function rely on the coordination of an extraordinarily complex set of neurodevelopmental events that involve genetic and environmental interactions. The past decade of behavioral epigenetics research has begun to shed light on mechanisms through which our experiences can interact with and become linked with our biology, providing a new framework to understand the brain’s ability to change as a result of experience (i.e. plasticity) and thus how behavior can arise.


provided compelling evidence for the contribution of gene-environment interactions. With the revolution of behavioural epigenetics, investigators then turned to epigenetic mechanisms

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Concluding remarks

Since the birth of behavioral epigenetics research, we have gained fascinating insight into the link between regulation of chromatin structure and plasticity. Studies have revealed that environmental adversity, for example in the form of social stress or traumatic experiences, can become encoded within epigenetic factors that control gene activity. Together, it has become clear that epigenetic mechanisms are poised to facilitate gene-environment communication throughout our lifespan. Epigenetic effects may also have implications for the stress susceptibility and well-being of future generations, providing a molecular mechanism to explain the transgenerational continuity of the effects of, for example, abuse and trauma. We certainly still lack a complete understanding of the cause-and-effect role of epigenetic mechanisms in brain development, function, and plasticity, but continued exploration of the regulatory role of epigenetic processes in aspects of normal and abnormal brain and behavior development will continue to be an informative approach for understanding the biology of risk and resilience for cognitive dysfunction and psychiatric disorders.


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