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应激、成瘾与恢复力的表观遗传学:治疗意义

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

作者信息

Cadet Jean Lud

机构信息

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

出版信息

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

Abstract

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.

摘要

物质使用障碍(SUDs)极为普遍。SUDs涉及暴饮暴食的恶性循环,随后是偶尔的戒断期,尽管接受了治疗,但仍会复发,并伴有不良的医学和心理社会后果。有确凿证据表明,早年和成年期的应激性生活事件是成瘾发展的风险因素,并作为触发复发的线索。然而,并非所有经历创伤性事件的个体都会对合法或非法药物成瘾,这一事实表明存在个体和/或家族性的复原力因素,可保护这些心理健康的个体。在此,我简要概述对应激性事件反应的表观遗传基础以及与滥用药物给药相关的表观遗传变化。我还将讨论复原力的心理生物学以及在复原力模型中观察到的表观遗传标记的变化。最后,我提出成瘾治疗应涉及认知和药理学方法,以增强高危个体的复原力。对于已经受到成瘾物质有害影响的患者,也应采用类似的方法。

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