Posener Joel A, Veldhuis Johannes D, Province Michael A, Williams Gordon H, Schatzberg Alan F
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA.
Psychoneuroendocrinology. 2004 Oct;29(9):1129-37. doi: 10.1016/j.psyneuen.2004.01.004.
Although evidence suggests that major depressive disorder (MDD) is associated with hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, research on basal HPA axis hormone levels in MDD patients has been inconclusive. Definitive characterization of basal cortisol and adrenocorticotropin (ACTH) secretion may be important for understanding the pathophysiology of this disorder. In recent years, a new approach to the analysis of basal hormone secretion has been developed involving the approximate entropy (ApEn) statistic, which represents the degree of disorderliness or serial irregularity in a time series of hormone levels. ApEn has been shown to reflect the degree of coordination in integrated network systems and has provided new insights into the pathophysiology of a number of endocrine conditions. In the study reported here, 15 medication-free men with MDD and 15 healthy control men were admitted to a General Clinical Research Center and had blood sampled for cortisol and ACTH determinations every hour over a 24-h period. The cortisol and ACTH time series were characterized with a cosinor analysis and with analysis of ApEn. Depressed patients and control subjects did not differ significantly on any parameter derived from the cosinor analysis or on several other standard indices of basal hormone secretion. However, the depressed men had significantly increased cortisol ApEn and significantly decreased ACTH ApEn compared with the healthy subjects. The ApEn findings suggest a loss of regulatory control over cortisol secretion, and possibly increased cortisol feedback on the pituitary in the depressed patients. Together, these results are most consistent with a primary abnormality of the adrenal gland and suggest that further investigation of adrenal gland physiology may be informative for the pathophysiology of depression.
尽管有证据表明重度抑郁症（MDD）与下丘脑 - 垂体 - 肾上腺（HPA）轴功能亢进有关，但关于MDD患者基础HPA轴激素水平的研究尚无定论。明确基础皮质醇和促肾上腺皮质激素（ACTH）分泌的特征对于理解这种疾病的病理生理学可能很重要。近年来，一种分析基础激素分泌的新方法已经开发出来，涉及近似熵（ApEn）统计量，它代表激素水平时间序列中的无序程度或序列不规则性。ApEn已被证明可以反映整合网络系统中的协调程度，并为多种内分泌疾病的病理生理学提供了新的见解。在本报告的研究中，15名未服用药物的MDD男性患者和15名健康对照男性被纳入综合临床研究中心，在24小时内每小时采集血样以测定皮质醇和ACTH。通过余弦分析和ApEn分析对皮质醇和ACTH时间序列进行特征描述。抑郁患者和对照受试者在余弦分析得出的任何参数或其他几个基础激素分泌标准指标上均无显著差异。然而，与健康受试者相比，抑郁男性的皮质醇ApEn显著增加，ACTH ApEn显著降低。ApEn的研究结果表明抑郁患者对皮质醇分泌的调节控制丧失，并且可能垂体上的皮质醇反馈增加。总之，这些结果与肾上腺的原发性异常最为一致，并表明进一步研究肾上腺生理学可能有助于了解抑郁症的病理生理学。
