Epigenetics of early child development.
Epigenetics of early child development.
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儿童早期发育的表观遗传学。
DOI：
10.3389/fpsyt.2011.00016
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发表时间：
2011
影响因子：
4.7
通讯作者：
Spengler D
中科院分区：
文献类型：
--
作者：
Murgatroyd C;Spengler D
全面的临床研究表明，早期的不利条件会严重影响发育中的大脑，并在以后的生活中增加对情绪障碍的脆弱性。在出生后的早期，大脑表现出高度的可塑性，这使得环境信号可以改变快速发展的回路的轨迹。早期生活中的逆境能够塑造依赖经验的压力调节途径的成熟，这些途径是潜在的情绪功能和内分泌对压力的反应，如下丘脑-垂体-肾上腺(HPA)系统，导致成年后长期改变的应激反应。到目前为止，人类群体中基因-环境相互作用的研究一直被流行病学所主导。然而，神经科学领域的最新研究现在正在通过具体解决基因-环境相互作用使个体倾向于精神病理学的机制来推进临床研究。为此，正在开发适当的动物模型，在这种模型中，可以以受控的方式操纵早期的环境因素。在这里，我们将回顾最近进行的研究，共同的目的是了解早期环境对大脑发育的影响，并讨论表观遗传机制在将早期生命条件转化为支撑大脑功能的基因表达的长期变化中的新发展作用。特别是，我们认为表观遗传机制可以在生命早期调节基因-环境对话，并引起成人生理和功能障碍的持续表观遗传编程，最终导致疾病。了解早期生活经历如何产生持久的表观遗传标记，从而增加精神障碍的风险，如何维持这些标记，以及如何逆转这些标记，正日益成为现代精神病学的一个重点，并应为及时的治疗干预铺平新的指导方针。
Comprehensive clinical studies show that adverse conditions in early life can severely impact the developing brain and increase vulnerability to mood disorders later in life. During early postnatal life the brain exhibits high plasticity which allows environmental signals to alter the trajectories of rapidly developing circuits. Adversity in early life is able to shape the experience-dependent maturation of stress-regulating pathways underlying emotional functions and endocrine responses to stress, such as the hypothalamo–pituitary–adrenal (HPA) system, leading to long-lasting altered stress responsivity during adulthood. To date, the study of gene–environment interactions in the human population has been dominated by epidemiology. However, recent research in the neuroscience field is now advancing clinical studies by addressing specifically the mechanisms by which gene–environment interactions can predispose individuals toward psychopathology. To this end, appropriate animal models are being developed in which early environmental factors can be manipulated in a controlled manner. Here we will review recent studies performed with the common aim of understanding the effects of the early environment in shaping brain development and discuss the newly developing role of epigenetic mechanisms in translating early life conditions into long-lasting changes in gene expression underpinning brain functions. Particularly, we argue that epigenetic mechanisms can mediate the gene–environment dialog in early life and give rise to persistent epigenetic programming of adult physiology and dysfunction eventually resulting in disease. Understanding how early life experiences can give rise to lasting epigenetic marks conferring increased risk for mental disorders, how they are maintained and how they could be reversed, is increasingly becoming a focus of modern psychiatry and should pave new guidelines for timely therapeutic interventions.