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Circadian Clock and Stress Interactions in the Molecular Biology of Psychiatric Disorders

  • Sleep Disorders (P Gehrman, Section Editor)
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Abstract

Many psychiatric disorders are characterized by circadian rhythm abnormalities, including disturbed sleep/wake cycles, changes in locomotor activity, and abnormal endocrine function. Animal models with mutations in circadian “clock genes” commonly show disturbances in reward processing, locomotor activity and novelty seeking behaviors, further supporting the idea of a connection between the circadian clock and psychiatric disorders. However, if circadian clock dysfunction is a common risk factor for multiple psychiatric disorders, it is unknown if and how these putative clock abnormalities could be expressed differently, and contribute to multiple, distinct phenotypes. One possible explanation is that the circadian clock modulates the biological responses to stressful environmental factors that vary with an individual’s experience. It is known that the circadian clock and the stress response systems are closely related: Circadian clock genes regulate the physiological sensitivity to and rhythmic release of glucocorticoids (GC). In turn, GCs have reciprocal effects on the clock. Since stressful life events or increased vulnerability to stress are risk factors for multiple psychiatric disorders, including post-traumatic stress disorder (PTSD), attention deficit hyperactivity disorder (ADHD), bipolar disorder (BD), major depressive disorder (MDD), alcohol use disorder (AUD) and schizophrenia (SCZ), we propose that modulation of the stress response is a common mechanism by which circadian clock genes affect these illnesses. Presently, we review how molecular components of the circadian clock may contribute to these six psychiatric disorders, and present the hypothesis that modulation of the stress response may constitute a common mechanism by which the circadian clock affects multiple psychiatric disorders.

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Acknowledgments

This work was supported by a Veterans Affairs Merit Award (1I01BX001146) to DKW, and a VA Career Development Award (1IK2BX001275) to MJM. The funders had no role in the analysis, decision to publish, or preparation of the manuscript.

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Conflict of Interest

Dominic Landgraf and Michael J. McCarthy have received a grant from the U.S. Department of Veterans Affairs for research on circadian rhythms and bipolar disorder.

David K. Welsh has received a grant from the U.S. Department of Veterans Affairs and consultancy fees from Orphagen Pharmaceuticals.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Veterans Affairs San Diego Healthcare System, San Diego, CA, USA

    Dominic Landgraf, Michael J. McCarthy & David K. Welsh

  2. Department of Psychiatry, and Center for Circadian Biology, University of California, San Diego, 9500 Gilman Drive, MC-0603, La Jolla, CA, USA

    Dominic Landgraf, Michael J. McCarthy & David K. Welsh

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  1. Dominic Landgraf
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  2. Michael J. McCarthy
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  3. David K. Welsh
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Correspondence to David K. Welsh.

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Dominic Landgraf and Michael J. McCarthy contributed equally to this work.

This article is part of the Topical Collection on Sleep Disorders

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Landgraf, D., McCarthy, M.J. & Welsh, D.K. Circadian Clock and Stress Interactions in the Molecular Biology of Psychiatric Disorders. Curr Psychiatry Rep 16, 483 (2014). https://doi.org/10.1007/s11920-014-0483-7

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