Carroll B J, Cassidy F, Naftolowitz D, Tatham N E, Wilson W H, Iranmanesh A, Liu P Y, Veldhuis J D
Pacific Behavioral Research Foundation, Carmel, CA, USA.
Acta Psychiatr Scand Suppl. 2007(433):90-103. doi: 10.1111/j.1600-0447.2007.00967.x.
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.
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.
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.
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.
抑郁症中介导高皮质醇血症的机制仍存在争议。采用生物标志物策略，我们研究了高皮质醇血症和非高皮质醇血症的抑郁症住院患者以及正常志愿者的促肾上腺皮质激素（ACTH）和皮质醇动态变化。
对24小时脉冲式分泌进行去卷积分析，对分泌规律性进行近似熵（ApEn）估计，对正向和反向ACTH - 皮质醇同步性进行交叉ApEn定量，以及对24小时节律性进行余弦回归分析。
高皮质醇血症与忧郁型和精神病性抑郁亚型密切相关。高皮质醇血症患者的ACTH和皮质醇分泌升高，主要由脉冲量增加介导。基础ACTH分泌增加，ACTH半衰期缩短，24小时平均ACTH浓度正常。皮质醇分泌以高度不规则模式增加（高ApEn），ACTH到皮质醇的交叉ApEn高（前馈耦合受损）。皮质醇对ACTH分泌模式的反馈正常。高皮质醇血症的抑郁症患者下丘脑 - 垂体 - 肾上腺（HPA）轴脉冲发生器的程序正常：ACTH脉冲频率、皮质醇脉冲频率、昼夜高峰相位和ACTH分泌的ApEn均正常。肾上腺皮质对内源性ACTH的反应性正常。非高皮质醇血症患者在ACTH调节参数上与高皮质醇血症患者相似，但总皮质醇分泌较低。
无论皮质醇水平如何，抑郁症住院患者均出现ACTH分泌增加，证实严重抑郁症中存在中枢HPA轴亢进。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、无序的基础皮质醇释放，这是忧郁型/精神病性抑郁症中生理应激的一个标志。
