Circadian disruption and human health
Open accessAbstract
Biomarkers of circadian rhythm and circadian disruptionAlthough the SCN rhythm cannot be directly measured in humans, the timing of melatonin onset and amplitude measured in plasma or saliva, or the melatonin metabolite 6-sulfatoxymelatonin in urine, are gold standard biomarkers of circadian rhythms.The collection of 24-hour urine samples is particularly useful to assess circadian amplitude of melatonin in special populations, such as pediatric patients in whom blood or salivary samples might be difficult to obtain (8), and has been shown to be a useful treatment-responsive biomarker of circadian disruption in neurologic diseases, such as Alzheimer's disease (AD) (9) and pediatric epilepsy (10).Although less direct, other commonly used measures include rest/ activity cycles derived from actigraphy, and other hormonal, metabolic, and cardiovascular rhythms (7).Circadian disruption is pervasive and can occur at multiple organizational levels, contributing to poor health outcomes at individual and population levels.Evidence points to a bidirectional relationship, in that circadian disruption increases disease severity and many diseases can disrupt circadian rhythms.Importantly, circadian disruption can increase the risk for the expression and development of neurologic, psychiatric, cardiometabolic, and immune disorders.Thus, harnessing the rich findings from preclinical and translational research in circadian biology to enhance health via circadian-based approaches represents a unique opportunity for personalized/precision medicine and overall societal well-being.In this Review, we discuss the implications of circadian disruption for human health using a bench-to-bedside approach.Evidence from preclinical and translational science is applied to a clinical and population-based approach.Given the broad implications of circadian regulation for human health, this Review focuses its discussion on selected examples in neurologic, psychiatric, metabolic, cardiovascular, allergic, and immunologic disorders that highlight the interrelatedness between circadian disruption and human disease and the potential of circadian-based interventions, such as bright light therapy and exogenous melatonin, as well as chronotherapy to improve and/or modify disease outcomes.
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These changes can lead to perturbations in sleep quantity and quality, rest-activity cycles, mood, and cognitive function, increasing susceptibility to death and morbidity.
“These changes can lead to perturbations in sleep quantity and quality, rest‐activity cycles, mood, and cognitive function, increasing susceptibility to death and morbidity [16].”
The most significant associations represent common chronic disease phenotypes that have been associated with circadian disruption.
“Here, the most significant associations represent common chronic disease phenotypes that have been associated with circadian disruption6,27.”
From Diurnal rhythms of wrist temperature are associated with future disease risk in the UK Biobank (2023) · cites this paper as [27]
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- Authors
- Fishbein, A. B., Knutson, K. L., & Zee, P. C.
- Affiliations
- Lurie Children's Hospital (US)
- Northwestern University (US)
- Venue
- Journal of Clinical Investigation
- Published
- 2021-10-01
- Volume
- 131
- Issue
- 19
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC8483747
- OpenAlex
- W3203847771
- Cited by
- 468
- References
- 241
- Citations by year
- 2026: 134 · 2025: 138 · 2024: 95 · 2023: 76 · 2022: 25
- FWCI
- 6.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (P01AG011412, R01AG059291)
- National Heart, Lung, and Blood Institute (R01HL140580, R01HL141881, T32HL007909)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (K23AR075108)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Keywords
- circadian rhythm disruption, circadian rhythm, melatonin, 6-sulfatoxymelatonin, biomarkers, suprachiasmatic nucleus, actigraphy, neurological disorders, mental illness, cardiometabolic disease, immune disorders, allergic diseases, chronotherapy, bright light therapy, exogenous melatonin, personalized medicine
- MeSH terms
- Mental Disorders, Cardiovascular Diseases, Circadian Rhythm, Humans, Metabolic Diseases, Public Health, Biomarkers, Neurodegenerative Diseases, Neurodevelopmental Disorders
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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