Department of Psychiatry and Center For Circadian Biology, University of California San Diego, La Jolla, CA, USA.
Department of Psychiatry and Center For Circadian Biology, University of California San Diego, La Jolla, CA, USA; Mental Health Service, VA San Diego Healthcare System, La Jolla, CA, USA.
Neurosci Lett. 2022 Aug 24;786:136772. doi: 10.1016/j.neulet.2022.136772. Epub 2022 Jul 4.
Bipolar disorder (BD) is characterized by disrupted circadian rhythms affecting sleep, arousal, and mood. Lithium is among the most effective mood stabilizer treatments for BD, and in addition to improving mood symptoms, stabilizes sleep and activity rhythms in treatment responsive patients. Across a variety of experimental models, lithium has effects on circadian rhythms. However, uncertainty exists as to whether these actions directly pertain to lithium's therapeutic effects. Here, we consider evidence from mechanistic studies in animals and cells and clinical trials in BD patients that identify associations between circadian rhythms and the therapeutic effects of lithium. Most evidence indicates that lithium has effects on cellular circadian rhythms and increases morningness behaviors in BD patients, changes that may contribute to the therapeutic effects of lithium. However, much of this evidence is limited by cross-sectional analyses and/or imprecise proxy markers of clinical outcomes and circadian rhythms in BD patients, while mechanistic studies rely on inference from animals or small numbers of patients . Further study may clarify the essential mechanisms underlying lithium responsive BD, better characterize the longitudinal changes in circadian rhythms in BD patients, and inform the development of therapeutic interventions targeting circadian rhythms.
双相情感障碍（BD）的特征是昼夜节律紊乱，影响睡眠、觉醒和情绪。锂是治疗 BD 最有效的情绪稳定剂之一，除了改善情绪症状外，还能稳定治疗反应患者的睡眠和活动节律。在各种实验模型中，锂对昼夜节律都有影响。然而，尚不确定这些作用是否直接与锂的治疗效果有关。在这里，我们考虑了来自动物和细胞的机制研究以及 BD 患者的临床试验的证据，这些证据确定了昼夜节律与锂治疗效果之间的关联。大多数证据表明锂对细胞昼夜节律有影响，并增加 BD 患者的早晨倾向行为，这些变化可能有助于锂的治疗效果。然而，由于横断面分析以及/或 BD 患者临床结果和昼夜节律的不精确替代标志物的限制，其中大部分证据有限，而机制研究则依赖于动物或少数患者的推断。进一步的研究可能会阐明锂反应性 BD 的基本机制，更好地描述 BD 患者昼夜节律的纵向变化，并为针对昼夜节律的治疗干预措施的发展提供信息。
