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Neurobiological and behavioral mechanisms of circadian rhythm disruption in bipolar disorder: A critical multi-disciplinary literature review and agenda for future research from the ISBD task force on chronobiology

Lookup NU author(s): Emeritus Professor Jan Scott



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


© 2021 The Authors. Bipolar Disorders published by John Wiley & Sons Ltd.Aim: Symptoms of bipolar disorder (BD) include changes in mood, activity, energy, sleep, and appetite. Since many of these processes are regulated by circadian function, circadian rhythm disturbance has been examined as a biological feature underlying BD. The International Society for Bipolar Disorders Chronobiology Task Force (CTF) was commissioned to review evidence for neurobiological and behavioral mechanisms pertinent to BD. Method: Drawing upon expertise in animal models, biomarkers, physiology, and behavior, CTF analyzed the relevant cross-disciplinary literature to precisely frame the discussion around circadian rhythm disruption in BD, highlight key findings, and for the first time integrate findings across levels of analysis to develop an internally consistent, coherent theoretical framework. Results: Evidence from multiple sources implicates the circadian system in mood regulation, with corresponding associations with BD diagnoses and mood-related traits reported across genetic, cellular, physiological, and behavioral domains. However, circadian disruption does not appear to be specific to BD and is present across a variety of high-risk, prodromal, and syndromic psychiatric disorders. Substantial variability and ambiguity among the definitions, concepts and assumptions underlying the research have limited replication and the emergence of consensus findings. Conclusions: Future research in circadian rhythms and its role in BD is warranted. Well-powered studies that carefully define associations between BD-related and chronobiologically-related constructs, and integrate across levels of analysis will be most illuminating.

Publication metadata

Author(s): McCarthy MJ, Gottlieb JF, Gonzalez R, McClung CA, Alloy LB, Cain S, Dulcis D, Etain B, Frey BN, Garbazza C, Ketchesin K, Landgraf D, Lee H-J, Marie-Claire C, Nusslock R, Porcu A, Porter R, Ritter P, Scott J, Smith D, Swartz HA, Murray G

Publication type: Review

Publication status: Published

Journal: Bipolar Disorders

Year: 2021

Volume: 24

Issue: 3

Pages: 232-263

Online publication date: 30/11/2021

Acceptance date: 02/04/2020

ISSN (print): 1398-5647

ISSN (electronic): 1399-5618

Publisher: John Wiley and Sons Inc


DOI: 10.1111/bdi.13165