The impact of early adverse experiences on brain systems involved in the pathophysiology of anxiety and affective disorders
The impact of early adverse experiences on brain systems involved in the pathophysiology of anxiety and affective disorders
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DOI：
10.1016/s0006-3223(99)00224-3
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发表时间：
1999-12-01
影响因子：
10.6
通讯作者：
Nemeroff, CB
中科院分区：
文献类型：
--
作者：
Heim, C;Nemeroff, CB
遗传和环境因素对主要精神疾病的发展的相对贡献一直存在争议。最近，有观察到早期的不良经历使个体在成年后易患情感性和焦虑性障碍，这一现象引起了人们的极大关注。促肾上腺皮质激素释放因子(CRF)是内分泌、自主神经、免疫和行为应激反应的中枢协调者。当集中给药时，CRF会产生许多让人想起急性应激和抑郁的生理和行为变化。此外，CRF还与多种焦虑症的发病机制有关，主要是通过连接杏仁核和蓝斑的CRF神经回路。临床研究已经提供了令人信服的证据，证明中枢性CRF在抑郁症中高分泌，在较小程度上，在一些焦虑症中也存在。主要来自临床前研究的证据表明，生命早期的压力会导致持续的中枢性CRF过度活动，并在成年后增加应激反应。因此，遗传倾向加上发育关键阶段的早期应激，可能导致神经生物学上易受压力影响的表型，并可能降低个体在进一步应激暴露时出现抑郁和焦虑的门槛。这一病理生理学模型可能为预防和治疗与生命早期应激相关的精神病理学提供新的方法。(C)1999年生物精神病学学会。
The relative contribution of genetic and environmental factors to the development of the major psychiatric disorders has long been debated. Recently, considerable attention has been given to the observations that adverse experiences early in life predispose individuals to the development of affective and anxiety disorders in adulthood. Corticotropin-releasing factor (CRF) is the central coordinator of the endocrinologic, autonomic, immunologic, and behavioral stress responses. When centrally administered, CRF produces many physiologic and behavioral changes reminiscent of both acute stress and depression. Moreover, CRF has also been implicated in the pathogenesis of a variety of anxiety disorders, mainly through CRF neurocircuits connecting the amygdala and the locus ceruleus. Clinical studies have provided convincing evidence for central CRF hypersecretion in depression and, to a lesser extent, in some anxiety disorders. Evidence mainly from preclinical studies suggests that stress early in life results in persistent central CRF hyperactivity and increased stress reactivity in adulthood. Thus, genetic disposition coupled with early stress in critical phases of development may result in a phenotype that is neurobiologically vulnerable to stress and may lower an individual's threshold for developing depression and anxiety upon further stress exposure. This pathophysiologic model may provide novel approaches to the prevention and treatment of psychopathology associated with stress early in life. (C) 1999 Society of Biological Psychiatry.