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The roles of melatonin and light in the pathophysiology and treatment of circadian rhythm sleep disorders

Nature Clinical Practice Neurology volume 4, pages 436–447 (2008)Cite this article

Abstract

Normal circadian rhythms are synchronized to a regular 24 h environmental light–dark cycle, and the suprachiasmatic nucleus and the hormone melatonin have important roles in this process. Desynchronization of circadian rhythms, as occurs in chronobiological disorders, can produce severe disturbances in sleep patterns. According to the International Classification of Sleep Disorders, circadian rhythm sleep disorders (CRSDs) include delayed sleep phase syndrome, advanced sleep phase syndrome, non-24 h sleep–wake disorder, jet lag and shift-work sleep disorder. Disturbances in the circadian phase position of plasma melatonin levels have been documented in all of these disorders. There is compelling evidence to implicate endogenous melatonin as an important mediator in CRSD pathophysiology, although further research involving large numbers of patients will be required to clarify whether the disruption of melatonin secretion is a causal factor in CRSDs. In this Review, we focus on the use of exogenous melatonin and light therapy to treat the disturbed sleep–wake rhythms seen in CRSDs.

Key Points

  • Circadian rhythm desynchronization is common among patients who present with sleep disorders

  • Circadian rhythm sleep disorders (CRSDs) include delayed sleep phase syndrome, advanced sleep phase syndrome, non-24 h sleep–wake rhythm disorder, shift-work sleep disorder and jet lag

  • The hormone melatonin is thought to have an important role in the synchronization of sleep–wake rhythm and rest–activity cycles with the light–dark cycle

  • Exogenous melatonin, sometimes in combination with light therapy, can be beneficial in resynchronizing sleep patterns in patients with CRSDs

  • Well-conducted, large clinical trials are warranted to further assess the efficacy and safety of chronotherapy as a treatment for CRSDs

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Authors and Affiliations

  1. SR Pandi-Perumal is the President and Chief Executive Officer of Somnogen Inc. and I Trakht is an Assistant Professor in the Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, College of Physicians and Surgeons at Columbia University, New York, NY, USA.,

    Seithikurippu R Pandi-Perumal & Ilya Trakht

  2. DW Spence is a PhD student at the University of Toronto, Toronto, ON, Canada.,

    D Warren Spence

  3. V Srinivasan is an Associate Professor in the Department of Physiology, School of Medical Sciences at University Sains Malaysia, Kota Bharu, Kelantan, Malaysia.,

    Venkataramanujan Srinivasan

  4. Y Dagan is a Senior Emergency Physician and Head of the Medical Education Department in the Faculty of Medicine at Tel Aviv University, Tel Aviv, Israel.,

    Yaron Dagan

  5. DP Cardinali is Professor of Physiology and Director of the Neuroscience Laboratory in the Faculty of Medicine at University of Buenos Aires, Buenos Aires, Argentina.,

    Daniel P Cardinali

Authors
  1. Seithikurippu R Pandi-Perumal
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  2. Ilya Trakht
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  3. D Warren Spence
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  4. Venkataramanujan Srinivasan
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  5. Yaron Dagan
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  6. Daniel P Cardinali
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Correspondence to Seithikurippu R Pandi-Perumal.

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Competing interests

SP Pandi-Perumal is a stockholder and the President and Chief Executive Officer of Somnogen, Inc.. The other authors declared no competing interests.

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Pandi-Perumal, S., Trakht, I., Spence, D. et al. The roles of melatonin and light in the pathophysiology and treatment of circadian rhythm sleep disorders. Nat Rev Neurol 4, 436–447 (2008). https://doi.org/10.1038/ncpneuro0847

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  • DOI: https://doi.org/10.1038/ncpneuro0847

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