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早期逆境与发展结果:遗传学、表观遗传学和整个生命周期社会经验的相互作用。

Early Adversity and Developmental Outcomes: Interaction Between Genetics, Epigenetics, and Social Experiences Across the Life Span.

机构信息

Department of Psychology, Columbia University, New York

出版信息

Perspect Psychol Sci. 2010 Sep;5(5):564-74. doi: 10.1177/1745691610383494.

Abstract

Longitudinal studies in humans demonstrate the association between prenatal and postnatal experiences of adversity and long-term changes in neurodevelopment. These studies raise the question of how experiences become incorporated at a biological level to induce persistent changes in functioning. Laboratory studies using animal models and recent analyses in human cohorts implicate epigenetic mechanisms as a possible route through which these environmental effects are achieved. In particular, there is evidence that changes in DNA methylation are associated with early life experiences with consequences for gene expression and behavior. Despite the potential stability of DNA methylation, it is apparent that this epigenetic mark can be dynamically modified through pharmacological targeting and behavioral experiences. Developmental plasticity may also be achieved through modification of the juvenile environment. Although these juvenile experiences may lead to common endpoints, there is evidence suggesting that the effects of early and later life experiences may be achieved by different molecular pathways. This review discusses evidence for the role of epigenetic mechanisms in shaping developmental trajectories in response to early life experience as well as the potential plasticity that can occur beyond the perinatal period. These studies have implications for approaches to intervention and suggest the importance of considering individual differences in genetic and epigenetic vulnerability in developing treatment strategies.

摘要

纵向研究在人类中证明了产前和产后逆境经历与神经发育的长期变化之间的关联。这些研究提出了一个问题,即经验如何在生物学层面上被整合,从而引起功能的持久变化。使用动物模型的实验室研究和最近在人类队列中的分析表明,表观遗传机制可能是这些环境影响实现的一种途径。特别是,有证据表明 DNA 甲基化的变化与早期生活经历有关,对基因表达和行为有影响。尽管 DNA 甲基化具有潜在的稳定性,但显然这种表观遗传标记可以通过药物靶向和行为经验进行动态修饰。通过改变幼年环境也可以实现发育可塑性。尽管这些幼年经历可能导致共同的终点,但有证据表明,早期和晚期生活经历的影响可能通过不同的分子途径实现。这篇综述讨论了表观遗传机制在塑造早期生活经历反应的发育轨迹中的作用的证据,以及在围产期之外可能发生的潜在可塑性。这些研究对干预方法有影响,并表明在制定治疗策略时考虑遗传和表观遗传脆弱性的个体差异的重要性。

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