Duncan Wallace C, Slonena Elizabeth E, Hejazi Nadia S, Brutsche Nancy, Park Lawrence T, Henter Ioline D, Ballard Elizabeth D, Zarate Carlos A
Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA,
Neuropsychiatr Dis Treat. 2018 Oct 16;14:2739-2748. doi: 10.2147/NDT.S172089. eCollection 2018.
This study examined the links between 24-hour activity patterns (specifically, amplitude and timing of wrist activity) and the persisting qualities of clinical antidepressant response to the glutamatergic modulator ketamine.
Twenty-four-hour activity patterns were compared across 5 days of 24-hour activity rhythms in patients with major depressive disorder who displayed either a brief antidepressant response (24-48 hours), a continued antidepressant response (>72 hours), or no antidepressant response to ketamine. These postinfusion-response profiles were then used retrospectively to examine cohort-specific fitted parameters at baseline, postinfusion day 1 (D1), and postinfusion D3.
Relative to the nonresponders, the cohort experiencing a brief antidepressant response had blunted 24-hour amplitude that extended from baseline through D3 and postketamine phase advance of activity on D1 that reverted to baseline on D3. Relative to the nonresponders, the cohort experiencing a continued antidepressant response to ketamine had phase-advanced activity at both baseline and D1, as well as increased amplitude on D1 and D3.
Taken together, the results suggest that the time course of antidepressant response to ketamine is influenced by underlying biological differences in motor activity timekeeping. These differences may provide clues that link durable mood response with the molecular machinery of the circadian system, thus leading to more effective interventions. In addition, biomarkers of preinfusion motor activity (eg, amplitude, timing) may be useful for recommending future individualized treatment interventions, to the extent that they help identify patients who may relapse quickly after treatment.
本研究探讨了24小时活动模式（具体而言，手腕活动的幅度和时间）与谷氨酸能调节剂氯胺酮临床抗抑郁反应持续特性之间的联系。
对重度抑郁症患者在5天24小时活动节律中的24小时活动模式进行比较，这些患者对氯胺酮表现出短暂抗抑郁反应（24 - 48小时）、持续抗抑郁反应（>72小时）或无抗抑郁反应。然后回顾性地使用这些输注后反应概况来检查基线、输注后第1天（D1）和输注后第3天特定队列的拟合参数。
相对于无反应者，经历短暂抗抑郁反应的队列从基线到D3的24小时幅度减弱，且在D1时活动的氯胺酮后相位提前，在D3时恢复到基线。相对于无反应者，对氯胺酮有持续抗抑郁反应的队列在基线和D1时活动均有相位提前，且在D1和D3时幅度增加。
综合来看，结果表明氯胺酮抗抑郁反应的时间进程受运动活动计时潜在生物学差异的影响。这些差异可能提供线索，将持久的情绪反应与昼夜节律系统的分子机制联系起来，从而带来更有效的干预措施。此外，输注前运动活动的生物标志物（如幅度、时间）可能有助于推荐未来的个体化治疗干预措施，前提是它们有助于识别治疗后可能迅速复发的患者。
