Mood Disorders Research Program and Laboratory for Clinical and Translational Neuroscience, Butler Hospital, Providence, RI 02906, USA.
Biol Psychiatry. 2013 Jan 1;73(1):15-23. doi: 10.1016/j.biopsych.2012.06.025. Epub 2012 Jul 24.
The long-term sequelae of adverse early-life experiences have long been a focus in psychiatry, with a historic neurobiological emphasis on physiological systems that are demonstrably stress-responsive, such as the hypothalamic-pituitary-adrenal axis and neuroimmune function. However, there has been increasing recognition in the general medical literature that such sequelae might encompass more pervasive alterations in health status and physiology. Recent findings in telomere biology have suggested a new avenue for exploring the adverse health effects of childhood maltreatment. Telomere length in proliferative tissues declines with cell replication and the effect can be accelerated by such factors as inflammation, oxidative stress, radiation, and toxins. Reduced telomere length, as a proxy for cellular aging, has been associated with numerous chronic somatic diseases that are generally considered to be diseases of aging, such as diabetes, cancer, and heart disease. More recently, shorter telomeres have been demonstrated in several psychiatric conditions, particularly depression. Sustained psychosocial stress of a variety of types in adulthood appears to be associated with shorter telomeres. Now, emerging work suggests a robust, and perhaps dose-dependent, relationship with early-life stress. These findings present new opportunities to reconceptualize the complex relationships between experience, physical and psychiatric disease, and aging.
长期以来，不良早期生活经历的后果一直是精神病学关注的焦点，历史上神经生物学强调的是明显对压力有反应的生理系统，如下丘脑-垂体-肾上腺轴和神经免疫功能。然而，一般医学文献中越来越认识到，这种后果可能包括更普遍的健康状况和生理变化。端粒生物学的最新发现为探索儿童期虐待对健康的不良影响提供了新的途径。增殖组织中的端粒长度随着细胞复制而减少，而炎症、氧化应激、辐射和毒素等因素会加速这种减少。端粒缩短，作为细胞衰老的替代指标，与许多被认为是衰老疾病的慢性躯体疾病有关，如糖尿病、癌症和心脏病。最近，在几种精神疾病中，特别是抑郁症中，已经证明了较短的端粒。成年期各种类型的持续心理社会压力似乎与端粒缩短有关。现在，新的研究工作表明，端粒与早期生活压力之间存在着强大的、可能是剂量依赖的关系。这些发现为重新构想经验、身体和精神疾病与衰老之间的复杂关系提供了新的机会。
