Circadian disruptions and brain clock dysregulation in mood disorders

Jorge Mendoza
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Abstract

The circadian system, composed of a network of brain and peripheral 24-hour clocks and oscillators, allows organisms to anticipate and synchronize to natural daily events. The day–night cycle is the dominant timing signal to align circadian clocks to the external time. Thereby, exposure to aberrant light–dark cycles leads to disruptions of the circadian system, evoking different health issues, including mental or affective ones. Humans with circadian misalignments, such as those observed in jet-lag-exposed people or shift workers, and animal models of clock disturbances show mood alterations such as anxiety and depressive-like behaviors. The mechanisms underlying the physiopathology of mood disorders in circadian disruption may imply an altered functioning of the main clock in the suprachiasmatic nucleus, from other central oscillators, or a loss of internal synchrony between them. This Review outlines the current knowledge on the link between circadian perturbations and mood disorders in humans and animal models, and the possible neurobiological mechanisms involved. This Review explores the link between mood disorders and circadian disruptions, including social jet lag and shift work, and offers new perspectives for therapeutic development in future chronobiology research.

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情绪障碍中的昼夜节律紊乱和大脑时钟失调
昼夜节律系统由大脑和外周 24 小时时钟和振荡器网络组成,使生物能够预测和同步自然界的日常事件。昼夜周期是使昼夜节律钟与外界时间保持一致的主要时间信号。因此,暴露于异常的光暗周期会导致昼夜节律系统紊乱,引发不同的健康问题,包括精神或情感问题。昼夜节律失调的人类,如时差暴露者或轮班工人,以及时钟紊乱的动物模型都会出现情绪改变,如焦虑和类似抑郁的行为。昼夜节律紊乱导致情绪失调的生理病理机制可能意味着嗜铬细胞上核的主时钟、其他中枢振荡器的功能发生了改变,或者它们之间失去了内部同步性。本综述概述了目前关于人类和动物模型中昼夜节律紊乱与情绪失调之间联系的知识,以及可能涉及的神经生物学机制。本综述探讨了情绪失调与昼夜节律紊乱(包括社会时差和轮班工作)之间的联系,并为未来时间生物学研究中的治疗发展提供了新的视角。
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