Working Paper Review Version 2 This version is not peer-reviewed

Chronobiology Revisited in Psychiatric Disorders: From a Translational Perspective

Version 1 : Received: 24 November 2019 / Approved: 24 November 2019 / Online: 24 November 2019 (16:44:37 CET)
Version 2 : Received: 15 May 2020 / Approved: 16 May 2020 / Online: 16 May 2020 (17:18:55 CEST)

A peer-reviewed article of this Preprint also exists.


Objective: Several lines of evidence support a relationship between circadian rhythms disruption in the onset, course, and maintenance of mental disorders. Despite the study of circadian phenotypes promising a decent understanding of the pathophysiologic or etiologic mechanisms of psychiatric entities, several questions still need to be addressed. In this review, we aimed to synthesize the literature investigating chronobiologic theories and their associations with psychiatric entities. Methods: The Medline, Embase, PsycInfo, and Scopus databases were comprehensively and systematically searched and articles published between January 1990 and October 2019 were reviewed. Different combinations of the relevant keywords were polled. We first introduced molecular elements and mechanisms of the circadian system to promote a better understanding of the chronobiologic implications of mental disorders. Then, we comprehensively and systematically reviewed circadian system studies in mood disorders, schizophrenia, and anxiety disorders. Results: Although subject characteristics and study designs vary across studies, current research has demonstrated that circadian pathologies, including genetic and neurohumoral alterations, represent the neural substrates of the pathophysiology of many psychiatric disorders. Impaired HPA-axis function-related glucocorticoid rhythm and disrupted melatonin homeostasis have been prominently demonstrated in schizophrenia and other psychotic disorders, while alterations of molecular expressions of circadian rhythm genes including CLOCK, PER, and CRY have been reported to be involved in the pathogenesis of mood disorders. Discussion: Further translational work is needed to identify the causal relationship between circadian physiology abnormalities and mental disorders and related psychopathology, and to develop sound pharmacologic interventions.


biological clocks; circadian rhythm disorders; mental disorders; melatonin; HPA-axis


Social Sciences, Behavior Sciences

Comments (1)

Comment 1
Received: 16 May 2020
Commenter: Yasin Hasan Balcioglu
Commenter's Conflict of Interests: Author
Comment: Abstract has been improved and definitions of circadian rhythms disruption have been clarified in relevant sections on the manuscript, according to reviewer feedback and comments.
The article has been accepted for publication in Psychiatry Investigation.
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