McEwen Bruce S
Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York 10021, USA.
Ment Retard Dev Disabil Res Rev. 2003;9(3):149-54. doi: 10.1002/mrdd.10074.
The stability of a child's early life has profound effects on physical and mental health, and unstable parent-child relationships, as well as abuse, can lead to behavioral disorders and increased mortality and morbidity from a wide variety of common diseases later in life. One common consequence, namely, depressive illness, is associated with chemical imbalances in the brain and hormonal dysregulation, constituting a form of allostatic load that alters interpretations of stimuli and influences, behavioral, and hormonal responses to potentially stressful situations. The brain not only encodes information and controls the behavioral responses but it is also changed structurally by those experiences. Structural changes in the hippocampus and amygdala, which are important brain structures for cognition and emotion, are representative of what may be occurring throughout the brain as a result of allostatic load resulting from the chronic stress of a disorder such as depression. Such structural changes include dendritic debranching and hypertrophy, cell proliferation, and synaptic remodeling; they are produced by the combined overactivity of stress hormones and endogenous neurotransmitters. These mediators are normally involved in adaptation, but can also promote damage when they are dysregulated and over-active. They are very likely to be strongly biased by early life experiences. The findings from animal models thus provide a basis for understanding potential mechanisms of environmental and developmental determinants of individual differences in human stress reactivity, as well as anxiety, depression, and a host of related systemic disorders. There is an increasing amount of translational research that is beginning to tie the basic research to clinical outcomes of individuals exposed to abusive or inconsistent care-giving in early life. A major goal of studies on this important topic is to define times in development and strategies for intervening to prevent or reverse the effects of adverse early life experiences. Although prevention is clearly the preferable route, some degree of reversal of psychopathology and pathophysiology caused by early life adversity appears to be an achievable goal.
儿童早期生活的稳定性对身心健康有着深远影响，不稳定的亲子关系以及虐待行为会导致行为障碍，并增加日后患各种常见疾病的死亡率和发病率。一个常见的后果，即抑郁症，与大脑中的化学失衡和激素失调有关，构成了一种应激负荷形式，它会改变对刺激的解读，并影响对潜在应激情况的行为和激素反应。大脑不仅对信息进行编码并控制行为反应，还会因这些经历而发生结构变化。海马体和杏仁核是大脑中对认知和情绪很重要的结构，它们的结构变化代表了由于抑郁症等疾病的慢性应激所导致的应激负荷在整个大脑中可能发生的情况。这种结构变化包括树突分支减少和肥大、细胞增殖以及突触重塑；它们是由应激激素和内源性神经递质的过度活动共同产生的。这些介质通常参与适应过程，但当它们失调和过度活跃时也会促进损伤。它们很可能受到早期生活经历的强烈影响。因此，动物模型的研究结果为理解人类应激反应、焦虑、抑郁以及一系列相关全身性疾病个体差异的环境和发育决定因素的潜在机制提供了基础。越来越多的转化研究开始将基础研究与早年遭受虐待或不一致照料的个体的临床结果联系起来。关于这个重要主题的研究的一个主要目标是确定发育过程中的关键时期以及干预策略，以预防或逆转早期生活不良经历的影响。虽然预防显然是更可取的途径，但逆转早期生活逆境所导致的精神病理学和病理生理学的一定程度影响似乎是一个可以实现的目标。
