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CNS Drugs

, Volume 33, Issue 10, pp 981–999 | Cite as

Pharmacological Manipulation of the Circadian Clock: A Possible Approach to the Management of Bipolar Disorder

  • Alessandra Porcu
  • Robert Gonzalez
  • Michael J. McCarthyEmail author
Review Article

Abstract

Bipolar disorder (BD) is a mood disorder with genetic and neurobiological underpinnings, characterized primarily by recurrent episodes of mania and depression, with notable disruptions in rhythmic behaviors such as sleep, energy, appetite and attention. The chronobiological links to BD are further supported by the effectiveness of various treatment modalities such as bright light, circadian phase advance, and mood-stabilizing drugs such as lithium that have effects on the circadian clock. Over the past 30 years, the neurobiology of the circadian clock has been exquisitely described and there now exists a detailed knowledge of key signaling pathways, neurotransmitters and signaling mechanisms that regulate various dimensions of circadian clock function. With this new wealth of information, it is becoming increasingly plausible that new drugs for BD could be made by targeting molecular elements of the circadian clock. However, circadian rhythms are multidimensional and complex, involving unique, time-dependent factors that are not typically considered in drug development. We review the organization of the circadian clock in the central nervous system and briefly summarize data implicating the circadian clock in BD. We then consider some of the unique aspects of the circadian clock as a drug target in BD, discuss key methodological considerations and evaluate some of the candidate clock pathways and systems that could serve as potential targets for novel mood stabilizers. We expect this work will serve as a roadmap to facilitate the development of compounds acting on the circadian clock for the treatment of BD.

Notes

Compliance with Ethical Standards

This work was conducted in accordance with all pertinent standards for ethical research.

Funding

MJM is supported by a VA Merit Award (U.S. Department of Veterans Affairs; BX003431) and a research award from the Prentiss Foundation. The funders had no role in the preparation of the manuscript or decision to publish.

Conflict of interest

MJM has received consulting fees from Janssen Pharmaceuticals in the past 12 months. AP and RG have no conflicts to report.

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Copyright information

© This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2019

Authors and Affiliations

  1. 1.Department of Psychiatry and Center for Circadian BiologyUniversity of California San DiegoLa JollaUSA
  2. 2.Psychiatry ServiceVA San Diego Healthcare SystemSan DiegoUSA
  3. 3.Department of PsychiatryPenn State Health Milton S. Hershey Medical CenterHersheyUSA

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