Current Issue

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

Received: 　　Accepted:

Corresponding author: 王晗　　E-mail:

DOI: 10.13294/j.aps.2025.0067

Citing This Article：

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