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Mol Neurobiol. 2016 Jan;53(1):545-560. doi: 10.1007/s12035-014-9040-y. Epub 2014 Dec 11.

Epigenetics of Stress, Addiction, and Resilience: Therapeutic Implications.

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Molecular Neuropsychiatry Research Branch, DHHS/NIH/NIDA Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD, 21224, USA.


Substance use disorders (SUDs) are highly prevalent. SUDs involve vicious cycles of binges followed by occasional periods of abstinence with recurrent relapses despite treatment and adverse medical and psychosocial consequences. There is convincing evidence that early and adult stressful life events are risks factors for the development of addiction and serve as cues that trigger relapses. Nevertheless, the fact that not all individuals who face traumatic events develop addiction to licit or illicit drugs suggests the existence of individual and/or familial resilient factors that protect these mentally healthy individuals. Here, I give a brief overview of the epigenetic bases of responses to stressful events and of epigenetic changes associated with the administration of drugs of abuse. I also discuss the psychobiology of resilience and alterations in epigenetic markers that have been observed in models of resilience. Finally, I suggest the possibility that treatment of addiction should involve cognitive and pharmacological approaches that enhance resilience in at risk individuals. Similar approaches should also be used with patients who have already succumbed to the nefarious effects of addictive substances.


Alcohol; Cocaine; DNA methylation; Heroin; Histone acetylation; Methamphetamine; Nicotine

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