University of Cambridge, Cambridge CB2 8AH, UK.
Dev Psychopathol. 2011 Nov;23(4):1017-37. doi: 10.1017/S0954579411000472.
Childhood adversity is associated with increased risk for onset of depressive episodes. This review will present evidence that allostatic overload of the hypothalamic-pituitary-adrenal axis (HPAA) partially mediates this association. The HPAA is the physiological system that regulates levels of the stress hormone cortisol. First, data from animals and humans has shown that early environmental adversity is associated with long-term dysregulation of the HPAA. This may occur due to permanent epigenetic modification of the glucocorticoid receptor. Second, data from humans has demonstrated that HPAA dysregulation is associated with increased risk of future depression onset in healthy individuals, and pharmacological correction of HPAA dysregulation reduces depressive symptoms. HPAA dysregulation may result in corticoid-mediated abnormalities in neurogenesis in early life and/or neurotoxicity on neural systems that subserve emotion and cognition.
童年逆境与抑郁发作的风险增加有关。这篇综述将提出证据表明，下丘脑-垂体-肾上腺轴（HPAA）的全身适应负荷部分介导了这种关联。HPAA 是调节应激激素皮质醇水平的生理系统。首先，来自动物和人类的数据表明，早期环境逆境与 HPAA 的长期失调有关。这可能是由于糖皮质激素受体的永久性表观遗传修饰所致。其次，来自人类的数据表明，HPAA 失调与健康个体未来抑郁发作的风险增加有关，而 HPAA 失调的药物纠正可减轻抑郁症状。HPAA 失调可能导致皮质类固醇介导的早期神经发生中的异常和/或对情感和认知起作用的神经毒性。
