Agorastos Agorastos, Pervanidou Panagiota, Chrousos George P, Baker Dewleen G
II. Department of Psychiatry, Division of Neurosciences, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Unit of Developmental and Behavioral Pediatrics, First Department of Pediatrics, School of Medicine, Aghia Sophia Children's Hospital, National and Kapodistrian University of Athens, Athens, Greece.
Front Psychiatry. 2019 Mar 11;10:118. doi: 10.3389/fpsyt.2019.00118. eCollection 2019.
Early life stressors display a high universal prevalence and constitute a major public health problem. Prolonged psychoneurobiological alterations as sequelae of early life stress (ELS) could represent a developmental risk factor and mediate risk for disease, leading to higher physical and mental morbidity rates in later life. ELS could exert a programming effect on sensitive neuronal brain networks related to the stress response during critical periods of development and thus lead to enduring hyper- or hypo-activation of the stress system and altered glucocorticoid signaling. In addition, alterations in emotional and autonomic reactivity, circadian rhythm disruption, functional and structural changes in the brain, as well as immune and metabolic dysregulation have been lately identified as important risk factors for a chronically impaired homeostatic balance after ELS. Furthermore, human genetic background and epigenetic modifications through stress-related gene expression could interact with these alterations and explain inter-individual variation in vulnerability or resilience to stress. This narrative review presents relevant evidence from mainly human research on the ten most acknowledged neurobiological allostatic pathways exerting enduring adverse effects of ELS even decades later (hypothalamic-pituitary-adrenal axis, autonomic nervous system, immune system and inflammation, oxidative stress, cardiovascular system, gut microbiome, sleep and circadian system, genetics, epigenetics, structural, and functional brain correlates). Although most findings back a causal relation between ELS and psychobiological maladjustment in later life, the precise developmental trajectories and their temporal coincidence has not been elucidated as yet. Future studies should prospectively investigate putative mediators and their temporal sequence, while considering the potentially delayed time-frame for their phenotypical expression. Better screening strategies for ELS are needed for a better individual prevention and treatment.
早期生活应激源普遍存在且构成了一个重大的公共卫生问题。作为早期生活应激（ELS）后遗症的长期心理神经生物学改变可能是一种发育风险因素，并介导疾病风险，导致晚年更高的身心发病率。ELS可能在发育的关键时期对与应激反应相关的敏感神经元脑网络产生编程效应，从而导致应激系统持久的过度或不足激活以及糖皮质激素信号改变。此外，情绪和自主反应性的改变、昼夜节律紊乱、大脑的功能和结构变化，以及免疫和代谢失调最近被确定为ELS后体内稳态平衡长期受损的重要风险因素。此外，人类遗传背景以及通过与应激相关的基因表达进行的表观遗传修饰可能与这些改变相互作用，并解释个体在应激易感性或恢复力方面的差异。这篇叙述性综述主要展示了来自人类研究的相关证据，涉及十条最公认的神经生物学适应性负荷途径，这些途径即使在数十年后仍会对ELS产生持久的不利影响（下丘脑 - 垂体 - 肾上腺轴、自主神经系统、免疫系统和炎症、氧化应激、心血管系统、肠道微生物群、睡眠和昼夜节律系统、遗传学、表观遗传学、大脑结构和功能相关性）。尽管大多数研究结果支持ELS与晚年心理生物学失调之间的因果关系，但精确的发育轨迹及其时间巧合尚未阐明。未来的研究应前瞻性地调查假定的中介因素及其时间顺序，同时考虑其表型表达的潜在延迟时间框架。为了更好地进行个体预防和治疗，需要更好的ELS筛查策略。
