Pathophysiology of hypercortisolism in depression
Pathophysiology of hypercortisolism in depression
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DOI：
10.1111/j.1600-0447.2007.00967.x
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发表时间：
2007-01-01
影响因子：
6.7
通讯作者：
Veldhuis, J. D.
中科院分区：
文献类型：
--
作者：
Carroll, B. J.;Cassidy, F.;Veldhuis, J. D.
目的：抑郁症高皮质醇血症的发病机制仍存在争议。采用生物标志物的策略，我们研究了促肾上腺皮质激素（ACTH）和皮质醇动力学在高皮质激素和非高皮质激素抑郁症住院患者，并在正常志愿者。方法：24小时脉动分泌的去卷积分析，近似熵（ApEn）估计分泌规律，交叉ApEn定量正向和反向ACTH-皮质醇同步性，和余弦回归的24小时节律性。结果：高皮质醇血症与抑郁症和精神病性抑郁亚型密切相关。高皮质激素血症患者ACTH和皮质醇分泌升高，主要由爆发性肿块增加介导。基础ACTH分泌增加，ACTH半衰期缩短，平均24小时ACTH浓度正常。皮质醇分泌以高度不规则的模式（高ApEn）增加，高ACTH ->皮质醇交叉ApEn（前馈耦合受损）。皮质醇介导的ACTH分泌模式反馈正常。高皮质激素性抑郁症患者的中枢下丘脑-垂体-肾上腺（HPA）轴脉冲发生器正常编程：ACTH脉冲频率、皮质醇脉冲频率、昼夜高峰期和ACTH分泌的ApEn正常。肾上腺皮质对内源性ACTH的反应性正常。非高皮质激素患者类似于高皮质激素患者的ACTH调节参数，但总皮质醇secrety.Conclusion：增加ACTH分泌发生在抑郁症住院患者无论皮质激素的状态，确认中央HPA轴的严重抑郁症。抑郁性高皮质醇血症是由于肾上腺皮质的额外变化导致ACTH非依赖性的基础皮质醇无序释放，这是精神病性抑郁症生理应激的标志。
Objective: The mechanisms mediating hypercortisolemia in depression remain controversial. Adopting the biomarker strategy, we studied adrenocorticotropin (ACTH) and cortisol dynamics in hypercortisolemic and non-hypercortisolemic depressed in-patients, and in normal volunteers.Method: Deconvolution analysis of 24-h pulsatile secretion, approximate entropy (ApEn) estimation of secretory regularity, cross-ApEn quantitation of forward and reverse ACTH-cortisol synchrony, and cosine regression of 24-h rhythmicity.Results: Hypercortisolemia was strongly associated with melancholic and psychotic depressive subtypes. Hypercortisolemic patients had elevated ACTH and cortisol secretion, mediated chiefly by increased burst masses. Basal ACTH secretion was increased, ACTH half-life was reduced, and mean 24-h ACTH concentration was normal. Cortisol secretion was increased in a highly irregular pattern (high ApEn), with high ACTH -> cortisol cross-ApEn (impaired feedforward coupling). Cortisol-mediated feedback on the secretory pattern of ACTH was normal. Hypercortisolemic depressed patients had normal programming of the central hypothalamo-pituitary-adrenal (HPA) axis pulse generator: ACTH pulse frequency, cortisol pulse frequency, circadian acrophases, and ApEn of ACTH secretion were normal. Responsiveness of the adrenal cortex to endogenous ACTH was normal. Non-hypercortisolemic patients resembled hypercortisolemic patients on ACTH regulatory parameters but had low total cortisol secretion.Conclusion: Increased ACTH secretion occurs in depressed in-patients regardless of cortisolemic status, confirming central HPA axis overdrive in severe depression. Depressive hypercortisolemia results from an additional change in the adrenal cortex that causes ACTH-independent, disorderly basal cortisol release, a sign of physiological stress in melancholic/psychotic depression.