Dept. of Psychiatry and Behavioral Sciences, Stanford University Medical School, 401 Quarry Road, Stanford, CA 94305-5730, United States.
J Psychiatr Res. 2010 Jan;44(2):69-74. doi: 10.1016/j.jpsychires.2009.06.012. Epub 2009 Dec 11.
Hypothalamic-pituitary-adrenal (HPA) axis and melatonin rhythm alterations have been independently reported in major depression (MDD) as well as in insomnia. In this pilot study, we link cortisol and melatonin rhythms and propose that the phase angle between cortisol acrophase (CA) and dim-light melatonin onset (20 pg/ml) (DLMO-20) may yield a useful state specific biomarker for MDD.
Six healthy (HC) and six depressed (MDD) psychotropic free subjects were admitted to the General Clinical Research Center. Blood was sampled for cortisol and melatonin from 1600h to 1000h, under dim lights (<20lux) and constant routine. Time for DLMO-20 and peak cortisol concentration was determined for each subject. Phase angle was computed as the difference in time between CA and DLMO-20.
Phase angle was significantly increased in MDD's versus HC's (13.40+/-1.61h. versus 11.61+/-1.66h, p=0.026). Using ROC analysis, a phase angle greater than 13.57h distinguished MDD's from HC's (sensitivity=0.83, specificity=1.0). Mean nocturnal melatonin (1600-1000h) was significantly decreased in MDD's versus HC's (22.67+/-9.08 pg/ml versus 47.82+/-14.76 pg/ml, p=0.015).
The phase angle between CA and DLMO-20 appears to distinguish HC's from MDD's and may be a useful biomarker to aid biologic assessment as well as treatment. Lower nocturnal melatonin in MDD's highlights its importance in MDD's pathophysiology. Additional study with larger sample size is needed to confirm the results of this pilot study. The mechanism for this phase angle difference and decreased melatonin, itself, requires further study.
独立研究表明，在重度抑郁症（MDD）以及失眠症患者中，下丘脑-垂体-肾上腺（HPA）轴和褪黑素节律都发生了改变。在这项初步研究中，我们将皮质醇和褪黑素节律联系起来，并提出皮质醇峰值（CA）和暗光褪黑素起始时间（20pg/ml）（DLMO-20）之间的相位角可能为 MDD 提供一个有用的特定状态生物标志物。
将六名健康对照（HC）和六名接受精神药物治疗的抑郁患者（MDD）纳入一般临床研究中心。在暗光（<20lux）和恒常作息下，从 1600 到 1000 小时采集血液样本，用于检测皮质醇和褪黑素。确定每位受试者的 DLMO-20 时间和皮质醇峰值。相位角计算为 CA 和 DLMO-20 之间的时间差。
MDD 患者的相位角明显高于 HC（13.40+/-1.61h. 与 11.61+/-1.66h，p=0.026）。使用 ROC 分析，相位角大于 13.57h 可区分 MDD 和 HC（敏感性=0.83，特异性=1.0）。MDD 患者的夜间平均褪黑素（1600-1000h）明显低于 HC（22.67+/-9.08pg/ml 与 47.82+/-14.76pg/ml，p=0.015）。
CA 和 DLMO-20 之间的相位角似乎可以区分 HC 和 MDD，可能是辅助生物学评估和治疗的有用生物标志物。MDD 患者夜间褪黑素水平较低突出了其在 MDD 病理生理学中的重要性。需要更大样本量的进一步研究来证实这项初步研究的结果。这种相位角差异和褪黑素减少的机制需要进一步研究。
