Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Curr Psychiatry Rep. 2013 Sep;15(9):394. doi: 10.1007/s11920-013-0394-z.
Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has well-described rapid antidepressant effects in clinical studies of individuals with treatment-resistant major depressive disorder (MDD). Preclinical studies investigating the effects of ketamine on brain-derived neurotrophic factor (BDNF) and on sleep slow wave activity (SWA) support its use as a prototype for investigating the neuroplastic mechanisms presumably involved in the mechanism of rapidly acting antidepressants. This review discusses human EEG slow wave sleep parameters and plasma BDNF as central and peripheral surrogate markers of plasticity, and their use in assessing ketamine's effects. Acutely, ketamine elevates BDNF levels, as well as early night SWA and high-amplitude slow waves; each of these measures correlates with change in mood in depressed patients who respond to ketamine. The slow wave effects are limited to the first night post-infusion, suggesting that their increase is part of an early cascade of events triggering improved mood. Increased total sleep and decreased waking occur during the first and second night post infusion, suggesting that these measures are associated with the enduring treatment response observed with ketamine.
氯胺酮是一种 N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，在治疗抵抗性重度抑郁症（MDD）患者的临床研究中具有明显的快速抗抑郁作用。研究氯胺酮对脑源性神经营养因子（BDNF）和睡眠慢波活动（SWA）影响的临床前研究支持将其作为研究快速作用抗抑郁药所涉及的神经可塑性机制的原型。本综述讨论了人类 EEG 慢波睡眠参数和血浆 BDNF 作为可塑性的中枢和外周替代标志物，及其在评估氯胺酮作用中的应用。氯胺酮可急性升高 BDNF 水平，以及夜间早期 SWA 和高振幅慢波；这些措施中的每一项都与对氯胺酮有反应的抑郁患者的情绪变化相关。慢波效应仅限于输注后第一晚，这表明它们的增加是触发情绪改善的早期级联事件的一部分。输注后第一和第二晚的总睡眠时间增加，觉醒时间减少，这表明这些措施与氯胺酮观察到的持久治疗反应有关。
