Quera Salva M A, Hartley S
Sleep Unit, Physiology Department, Hôpital Raymond Poincaré, 104 Boulevard Raymond Poincaré, 92380 Garches, France.
J Cent Nerv Syst Dis. 2012 Jan 4;4:15-26. doi: 10.4137/JCNSD.S4103. Print 2012.
Recent advances in the understanding of circadian rhythms have led to an interest in the treatment of major depressive disorder with chronobiotic agents. Many tissues have autonomous circadian rhythms, which are orchestrated by the master clock, situated in the suprachiasmatic nucleus (SNC). Melatonin (N-acetyl-5-hydroxytryptamine) is secreted from the pineal gland during darkness. Melatonin acts mainly on MT1 and MT2 receptors, which are present in the SNC, regulating physiological and neuroendocrine functions, including circadian entrainment, referred to as the chronobiotic effet. Circadian rhythms has been shown to be either misaligned or phase shifted or decreased in amplitude in both acute episodes and relapse of major depressive disorder (MDD) and bipolar disorder. Manipulation of circadian rhythms either using physical treatments (such as high intensity light) or behavioral therapy has shown promise in improving symptoms. Pharmacotherapy using melatonin and pure melatonin receptor agonists, while improving sleep, has not been shown to improve symptoms of depression. A novel antidepressant, agomelatine, combines 5HT2c antagonist and melatonin agonist action, and has shown promise in both acute treatment of MDD and in preventing relapse.
近年来，对昼夜节律的理解取得了进展，引发了人们对使用生物钟调节药物治疗重度抑郁症的兴趣。许多组织都有自主的昼夜节律，这些节律由位于视交叉上核（SNC）的主时钟协调。褪黑素（N-乙酰-5-羟色胺）在黑暗期间从松果体分泌。褪黑素主要作用于SNC中存在的MT1和MT2受体，调节生理和神经内分泌功能，包括昼夜节律调整，即生物钟效应。研究表明，在重度抑郁症（MDD）和双相情感障碍的急性发作和复发中，昼夜节律要么失调，要么相位偏移，要么振幅降低。使用物理治疗（如高强度光照）或行为疗法来调节昼夜节律，已显示出改善症状的前景。使用褪黑素和纯褪黑素受体激动剂进行药物治疗，虽然能改善睡眠，但尚未显示出能改善抑郁症状。一种新型抗抑郁药阿戈美拉汀兼具5HT2c拮抗剂和褪黑素激动剂的作用，在MDD的急性治疗和预防复发方面都显示出了前景。
