Developing Biomarker Arrays Predicting Sleep and Circadian-Coupled Risks to Health
Open accessAbstract
This is not an industry supported study. Dr. Dijk has received research support from GW Pharma, Lilly, and Janssen and has consulted for Servier and Shire. Dr. Gehrman has received research support from Merck and has consulted for Johnson & Johnson. The other authors have indicated no financial conflicts of interest. The impact of advances in sleep and circadian sciences over the last 20 years on medicine, health, and public safety has been limited in part by the lack of availability of objective tools capable of quantifying sleep and circadian function in point-of-care (p-o-c) settings. This whitepaper is a product of a workshop that was designed to bring together thought-leaders in biomarker development, experts in sleep-circadian biology and sleep disorders to identify barriers and opportunities informing the future development of p-o-c diagnostic tools. The workshop entitled, “Developing Biomarker Arrays Predicting Sleep and Circadian-Coupled Risks to Health,” was held in Bethesda April 27–28 2015, and was jointly sponsored by the National Heart Lung and Blood Institute, National Institute on Aging and the Sleep Research Society (hereafter referred to as the biomarker workshop, (http://www.nhlbi.nih.gov/research/reports). The Sleep Research Society supported a number of early career investigators to attend the workshop. They contributed to the writing of this whitepaper. A biomarker is a “biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, condition or disease.”1,2 For the purpose of this whitepaper, “biomarkers” include quantifiable molecules and chemical properties of easily accessible biological samples (e.g., blood, urine, saliva). An ultimate goal is the development of robust and practical approaches for p-o-c or contact implementation in population-based research and most importantly, for clinical applications to enhance sleep and circadian health. Biomarkers to assess current alertness status, sleep health and circadian function are needed for: research to further understanding of sleep and circadian health science, p-o-c diagnosis of sleep and circadian disorders, for prognosis and to evaluate the risk of associated heart, lung, blood, and aging diseases and disorders, and to assess the adequacy of therapy. The ideal biomarker would show high sensitivity (correctly identify the state and degree of acute sleep loss, and possibly even duration that such a status has been ongoing), specificity (correctly identify the presence/absence of a chronic sleep deficiency, such as would be useful in an annual primary care medical visit). However, the field is currently without any viable biomarkers measurable in easily accessible bio-specimens. The availability of objective platforms capable of quantifying sleep and circadian function will ultimately determine whether advances in understanding sleep and circadian biology can be applied to improve health and disease management and reduce risks to health and public safety. In parallel with the development of p-o-c biomarkers, which take years to develop, there is urgent need to enhance and validate biosensors, mobile and wearable technologies that can be used in population phenotyping to accurately track sleep and circadian physiology and behavior. Such wearable technologies may facilitate the phenotyping needed to validate biomarkers, but in addition, will provide valuable information that will be useful for improving discovery, clinical diagnostics and intervention, as well as self-management of sleep for wellness. Together these efforts to develop biomarkers and biosensors will position the field for participation in the Million Vet Program (http://www.research.va.gov/MVP/) and the Precision Medicine Initiatives (http://www.nih.gov/precision-medicine-initiative-cohort-program). With diagnostic tools for p-o-c measurement of sleep and circadian function, medical care and physician practices addressing sleep and circadian disorders and risk for metabolic and other diseases, will be vastly improved, translating into lower health care costs and a healthier population. A marker of acute sleep loss that tracks alertness and predicts impaired behavioral function and performance relevant to fitness for duty might be used for roadside screening to assess sleep loss as a risk to performance and safe operation of a vehicle. Biomarker detection, sensitive enough to detect a single night of sleep loss would need to be developed with consideration of individual differences, including age and sex. Further, baseline data would likely be required to establish a reliable comparison for subsequent detection of change. Individuals vary in vulnerability to sleep loss and research is needed to elucidate benchmarks of normality. A marker of chronic sleep loss that predicts risks to health reflecting long term deficiency in duration, timing, or quality of sleep might be used in conjunction with the annual physical exam
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In humans, NREM sleep enhancing or intensifying effects are restricted to times of very mild host response activation, whereas stronger responses characterized by large cytokine increases and fever caused sleep disruption.
“in humans, NREM sleep enhancing or intensifying effects are restricted to times of very mild host response activation, whereas stronger responses characterized by large cytokine increases and fever caused sleep disruption (224, 396, 442).”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [396]
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Elevated oxidative stress biomarkers in adults with segmented sleep patterns
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Sleep, Circadian Rhythms, and Fatigue Management in Space Flight Operations
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Self-citationPlease forgive our appearance while under biomarker construction
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Self-citationTsimakouridze, E. V. (2017) · The Atrium (University of Guelph)
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- Authors
- Mullington, J. M., Abbott, S. M., Carroll, J. E., Davis, C. J., Dijk, D.-J., Dinges, D. F., Gehrman, P. R., Ginsburg, G. S., Gozal, D., Haack, M., Lim, D. C., Macrea, M., Pack, A. I., Plante, D. T., Teske, J. A., & Zee, P. C.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Northwestern University (US)
- University of California, Los Angeles (US)
- Washington State University Spokane (US)
- University of Surrey (GB)
- University of Pennsylvania (US)
- Duke University (US)
- University of Chicago (US)
- Salem VA Medical Center (US)
- University of Arizona (US)
- Corresponding author
- Mullington, Janet M.
- ORCID
- Venue
- Sleep
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-04
- Volume
- 39
- Issue
- 4
- Pages
- 727-736
- ISSN
- 0161-8105 (ISSN-L)
- 1550-9109
- PMC
- PMC4791606
- OpenAlex
- W2295625872
- Cited by
- 105
- References
- 88
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 8 · 2023: 10 · 2022: 14 · 2021: 11 · 2020: 12 · 2019: 13 · 2018: 13 · 2017: 7 · 2016: 6
- FWCI
- 8.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- SLEEP (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Surrey Research Insight Open Access (The University of Surrey) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Keywords
- biomarkers, circadian biomarkers, sleep biomarkers, point-of-care testing, sleep disorders, circadian rhythm disorders, sleep deprivation, clinical translation, sleep health, circadian health, prognosis, salivary biomarkers, blood biomarkers, urinary biomarkers, primary care
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