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Modeling the Influence of Chronic Sleep Restriction on Cortisol Circadian Rhythms, with Implications for Metabolic Disorders

1
Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02139, USA
2
Department of Systems and Computational Biology, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India
3
Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, USA
4
Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA
5
Department of Psychiatry, New York Langone Medical School, New York, NY 10016, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Victor Gault
Metabolites 2021, 11(8), 483; https://doi.org/10.3390/metabo11080483
Received: 13 June 2021 / Revised: 19 July 2021 / Accepted: 20 July 2021 / Published: 27 July 2021
(This article belongs to the Special Issue Circadian Disruption and Metabolic Disorder)
Chronic sleep deficiency is prevalent in modern society and is associated with increased risk of metabolic and other diseases. While the mechanisms by which chronic sleep deficiency induces pathophysiological changes are yet to be elucidated, the hypothalamic–pituitary–adrenal (HPA) axis may be an important mediator of these effects. Cortisol, the primary hormone of the HPA axis, exhibits robust circadian rhythmicity and is moderately influenced by sleep and wake states and other physiology. Several studies have explored the effects of acute or chronic sleep deficiency (i.e., usually from self-selected chronic sleep restriction, CSR) on the HPA axis. Quantifying long-term changes in the circadian rhythm of cortisol under CSR in controlled conditions is inadequately studied due to practical limitations. We use a semi-mechanistic mathematical model of the HPA axis and the sleep/wake cycle to explore the influence of CSR on cortisol circadian rhythmicity. In qualitative agreement with experimental findings, model simulations predict that CSR results in physiologically relevant disruptions in the phase and amplitude of the cortisol rhythm. The mathematical model presented in this work provides a mechanistic framework to further explore how CSR might lead to HPA axis disruption and subsequent development of chronic metabolic complications. View Full-Text
Keywords: mathematical modeling; HPA axis; cortisol; sleep/wake cycle; sleep restriction; circadian rhythms mathematical modeling; HPA axis; cortisol; sleep/wake cycle; sleep restriction; circadian rhythms
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MDPI and ACS Style

Rao, R.; Somvanshi, P.; Klerman, E.B.; Marmar, C.; Doyle, F.J., III. Modeling the Influence of Chronic Sleep Restriction on Cortisol Circadian Rhythms, with Implications for Metabolic Disorders. Metabolites 2021, 11, 483. https://doi.org/10.3390/metabo11080483

AMA Style

Rao R, Somvanshi P, Klerman EB, Marmar C, Doyle FJ III. Modeling the Influence of Chronic Sleep Restriction on Cortisol Circadian Rhythms, with Implications for Metabolic Disorders. Metabolites. 2021; 11(8):483. https://doi.org/10.3390/metabo11080483

Chicago/Turabian Style

Rao, Rohit, Pramod Somvanshi, Elizabeth B. Klerman, Charles Marmar, and Francis J. Doyle III. 2021. "Modeling the Influence of Chronic Sleep Restriction on Cortisol Circadian Rhythms, with Implications for Metabolic Disorders" Metabolites 11, no. 8: 483. https://doi.org/10.3390/metabo11080483

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