当期文章

生物节律及其在抑郁症发病机制和治疗中的作用

SMITH William Kojo^1,2, 仲兆民^1,2, 王璨紫³, HASSAN Najm Ul^1,2, KHAN Moheb^1,2, 王晗^1,*

¹苏州大学生物钟研究中心，苏州 215123；²苏州大学基础医学院，江苏省重大脑疾病创新药物研发及转化重点实验室，苏州 215123；³苏州德威国际学校，苏州 215000

摘要

重度抑郁症(major depressive disorder, MDD)影响着世界各地的人群，然而其病因复杂，至今仍未完全阐明。本综述旨在评估抑郁症及其调控机制，以及其与生物节律相互作用的最新进展。生物节律是每日周期性光暗循环的内在表征。越来越多的证据表明，抑郁症及其相关精神障碍与生物节律紊乱有关。尤其是，因为生物节律系统失调会增加罹患抑郁症的可能性，抑郁症常与生物节律异常相关。抑郁症患者体内多种节律紊乱的事实表明这些紊乱并非局限于单一的节律，而是涉及分子生物节律的核心机制。睡眠-觉醒周期是抑郁症患者常被扰乱的节律之一，而且其往往会导致其他节律紊乱。抑郁症患者表现出的生物节律紊乱以及基于时间生物学的治疗的快速有效性，凸显了生物节律系统是抑郁症治疗的关键靶点。本综述评估了抑郁症发病率上升的证据，并探讨了包括生物节律失调在内的促成因素。我们还讨论了抑郁症发病机制的关键假说、潜在病因和相关动物模型，并强调了导致抑郁症负担加重的潜在机制，以及了解这些因素对于改善预防和治疗策略的重要性。

关键词： 生物节律; 睡眠-觉醒周期; 抑郁症; 治疗学; 动物模型

Circadian rhythms and their roles in the pathogenesis and treatment of depression

SMITH William Kojo^1,2, ZHONG Zhao-Min^1,2, WANG Willow Tsanzi³, HASSAN Najm Ul^1,2, KHAN Moheb^1,2, WANG Han^1,*

¹Center for Circadian Clocks, Soochow University, Suzhou 215123, China；²Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, School of Basic Medical Sciences, Soochow University, Suzhou 215123, China；³Dulwich College Suzhou, Suzhou 215000, China

Abstract

Major depressive disorder (MDD) affects people all over the world, and yet, its etiology is complex and remains incompletely understood. In this review, we aim to assess recent advances in understanding depression and its regulation, as well as its interaction with circadian rhythms. Circadian rhythms are internalized representations of the periodic daily light and dark cycles. Accumulating evidence has shown that MDD and the related mental disorders are associated with disrupted circadian rhythms. In particular, depression has often been linked to abnormalities in circadian rhythms because dysregulation of the circadian system increases susceptibility to MDD. The fact that several rhythms are disrupted in depressed patients suggests that these disruptions are not restricted to any one rhythm but rather involve the molecular circadian clock core machinery. The sleep-wake cycle is one rhythm that is often disrupted in depression, which often leads to disturbances in other rhythms. The circadian disruptions manifested in depressed patients and the effectiveness and fast action of chronobiologically based treatments highlight the circadian system as a key therapeutic target in the treatment of depression. This review assesses the evidence on rising depression rates and examines their contributing factors, including circadian misalignment. We discuss key hypotheses underlying depression pathogenesis, potential etiology, and relevant animal models, and underscore potential mechanisms driving depression's growing burden and how understanding these factors is critical for improving prevention and treatment strategies.

Key words: circadian rhythms; sleep-wake cycle; depression; therapeutics; animal models

收稿日期：　　录用日期：

通讯作者：王晗　　E-mail:

DOI: 10.13294/j.aps.2025.0067

引用本文：

SMITH William Kojo, 仲兆民, 王璨紫, HASSAN Najm Ul, KHAN Moheb, 王晗. 生物节律及其在抑郁症发病机制和治疗中的作用[J]. 生理学报 2025; 77 (4): 689-711.

SMITH William Kojo, ZHONG Zhao-Min, WANG Willow Tsanzi, HASSAN Najm Ul, KHAN Moheb, WANG Han. Circadian rhythms and their roles in the pathogenesis and treatment of depression. Acta Physiol Sin 2025; 77 (4): 689-711