Barden N, Reul J M, Holsboer F
Max-Planck Institute of Psychiatry, Munich, Germany.
Trends Neurosci. 1995 Jan;18(1):6-11. doi: 10.1016/0166-2236(95)93942-q.
Patients suffering from severe depression often show an increased activity of the hypothalamic-pituitary-adrenocortical (HPA) system, a premature escape from the cortisol suppressant action of dexamethasone, and a number of other neuroendocrine changes. This might be explained by defective glucocorticoid feedback inhibition. Normalization of the hyperactive HPA system occurs during successful antidepressant pharmacotherapy of depressive illness, and this could be achieved by antidepressant-induced increases in the cellular corticosteroid receptors, rendering the HPA system more susceptible to feedback inhibition by cortisol. Both mineralocorticoid- and glucocorticoid-receptor mRNA levels and hormone-binding activities are found to be increased following treatment of different cell lines or animals with antidepressants. Since the timecourse of antidepressant actions on corticosteroid receptors follows more closely that of clinical improvement of depression, antidepressants might elevate mood in depressives through their long-term effects on HPA regulation.
患有严重抑郁症的患者通常表现出下丘脑 - 垂体 - 肾上腺皮质（HPA）系统活性增加、对地塞米松的皮质醇抑制作用过早逃逸以及许多其他神经内分泌变化。这可能是由于糖皮质激素反馈抑制缺陷所致。在抑郁症的成功抗抑郁药物治疗期间，过度活跃的HPA系统会恢复正常，这可以通过抗抑郁药诱导细胞内皮质类固醇受体增加来实现，使HPA系统更容易受到皮质醇的反馈抑制。在用抗抑郁药治疗不同细胞系或动物后，发现盐皮质激素和糖皮质激素受体的mRNA水平以及激素结合活性均增加。由于抗抑郁药对皮质类固醇受体的作用时间进程与抑郁症临床改善的时间进程更为密切相关，抗抑郁药可能通过其对HPA调节的长期作用来提升抑郁症患者的情绪。
