Koenigsberg Harold W, Teicher Martin H, Mitropoulou Vivian, Navalta Carryl, New Antonia S, Trestman Robert, Siever Larry J
Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA.
J Psychiatr Res. 2004 Sep-Oct;38(5):503-11. doi: 10.1016/j.jpsychires.2004.03.006.
Depression is associated with alterations in hormone and catecholamine circadian rhythms. Analysis of these alterations has the potential to distinguish between three neurobiological models of depression, the catecholamine model, the phase advance model and the dysregulation model. Although a number of studies of 24-h rhythms have been reported, inconsistencies among the findings have complicated efforts to model the chronobiology of depression. The present study takes advantage of frequent plasma sampling over the 24-h period and a multioscillator cosinor model to fit the 24-h rhythms.
Plasma levels of norepinephrine, cortisol, prolacatin and growth hormone were sampled at 30-min intervals, and MHPG at 60-min intervals, over a 24-h period in 22 patients with major depressive disorder and 20 healthy control volunteers.
The depressed patients had phase advanced circadian rhythms for cortisol, norepinephrine and MHPG, phase advanced hemicircadian rhythms for cortisol and prolactin, and a phase advanced ultradian rhythm for prolactin compared to healthy control subjects. In addition, the rhythm-corrected 24-h mean value (mesor) of norepinephrine was lower in the depressed patients compared to the healthy controls. There also was a poorer goodness-of-fit for norepinephrine to the circadian oscillator in the depressed patients relative to the healthy controls.
These findings provide partial support for the dysregulation model of depression and are consistent with those studies that have found phase advances in cortisol, norepinephrine and MHPG rhythms in depression.
抑郁症与激素和儿茶酚胺昼夜节律的改变有关。对这些改变进行分析有可能区分抑郁症的三种神经生物学模型,即儿茶酚胺模型、相位提前模型和调节失调模型。尽管已经报道了许多关于24小时节律的研究,但研究结果之间的不一致使得建立抑郁症时间生物学模型的努力变得复杂。本研究利用24小时内频繁的血浆采样和多振荡器余弦分析模型来拟合24小时节律。
在24小时内,对22名重度抑郁症患者和20名健康对照志愿者每隔30分钟采集一次去甲肾上腺素、皮质醇、催乳素和生长激素的血浆水平,每隔60分钟采集一次3-甲氧基-4-羟基苯乙二醇(MHPG)。
与健康对照受试者相比,抑郁症患者的皮质醇、去甲肾上腺素和MHPG的昼夜节律相位提前,皮质醇和催乳素的半昼夜节律相位提前,催乳素的超昼夜节律相位提前。此外,抑郁症患者去甲肾上腺素的节律校正24小时平均值(中值)低于健康对照组。与健康对照组相比,抑郁症患者去甲肾上腺素与昼夜振荡器的拟合优度也较差。
这些发现为抑郁症的调节失调模型提供了部分支持,并且与那些发现抑郁症患者皮质醇、去甲肾上腺素和MHPG节律相位提前的研究结果一致。