Beyond the symptom: the biology of fatigue

David M Raizen¹, Janet Mullington², Christelle Anaclet³, Gerard Clarke⁴, Hugo Critchley⁵, Robert Dantzer⁶, Ronald Davis⁷, Kelly L Drew⁸, Josh Fessel⁹, Patrick M Fuller³, Erin M Gibson¹⁰, Mary Harrington¹¹, W Ian Lipkin¹², Elizabeth B Klerman^{13

14}, Nancy Klimas¹⁵, Anthony L Komaroff¹⁴, Walter Koroshetz¹⁶, Lauren Krupp¹⁷, Anna Kuppuswamy¹⁸, Julie Lasselin¹⁹, Laura D Lewis²⁰, Pierre J Magistretti²¹, Heidi Y Matos¹⁶, Christine Miaskowski²², Andrew H Miller²³, Avindra Nath¹⁶, Maiken Nedergaard²⁴, Mark R Opp²⁵, Marylyn D Ritchie²⁶, Dragana Rogulja²⁷, Asya Rolls²⁸, John D Salamone²⁹, Clifford Saper², Vicky Whittemore¹⁶, Glenn Wylie³⁰, Jarred Younger³¹, Phyllis C Zee³², H Craig Heller³³

Affiliations

¹ Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
² Department of Neurology, Harvard Medical School, Boston, MA, USA.
³ Department of Neurological Surgery, University of California, Davis School of Medicine, Sacramento, CA, USA.
⁴ Department of Psychiatry and Neurobehavioural Science, and APC Microbiome Ireland, University College Cork, Cork, Ireland.
⁵ Brighton and Sussex Medical School Department of Neuroscience, University of Sussex, Brighton, UK.
⁶ Department of Symptom Research, Division of Internal Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁷ Department of Biochemistry and Genetics, Stanford University, Palo Alto, CA, USA.
⁸ Department of Chemistry and Biochemistry, Institute of Arctic Biology, Center for Transformative Research in Metabolism, University of Alaska Fairbanks, Fairbanks, AK, USA.
⁹ Division of Clinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA.
¹⁰ Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, CA, USA.
¹¹ Department of Psychology, Neuroscience Program, Smith College, Northampton, MA, USA.
¹² Center for Infection and Immunity, and Departments of Neurology and Pathology, Columbia University, New York City, NY, USA.
¹³ Division of Sleep Medicine, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
¹⁴ Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
¹⁵ Department of Clinical Immunology, College of Osteopathic Medicine, Nova Southeastern University, Ft. Lauderdale, FL, USA.
¹⁶ National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
¹⁷ Department of Neurology, NYU Grossman School of Medicine, NYC, NY, USA.
¹⁸ University College London, Queen Square Institute of Neurology, London, England.
¹⁹ Department of Psychology, Stockholm University, Stockholm, Sweden.
²⁰ Center for Systems Neuroscience, Department of Biomedical Engineering, Boston University, Boston, MA, USA.
²¹ Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology, Thuwal, Kingdom of Saudi Arabia.
²² Department of Physiological Nursing, School of Nursing, University of California, San Francisco, CA, USA.
²³ Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
²⁴ Departments of Neurology and Neurosurgery, University of Rochester Medical Center, Rochester, NY, USA.
²⁵ Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA.
²⁶ Department of Genetics, Institute for Biomedical Informatics, Penn Center for Precision Medicine, University of Pennsylvania, Philadelphia, PA, USA.
²⁷ Department of Neurobiology, Harvard University, Boston, MA, USA.
²⁸ Rappaport Institute for Medical Research, Technion, Israel Institute of Technology, Haifa, Israel.
²⁹ Department of Psychological Sciences, University of Connecticut, Storrs, CT, USA.
³⁰ Rocco Ortenzio Neuroimaging Center at Kessler Foundation, East Hanover, NJ, USA.
³¹ Department of Psychology, University of Alabama, Birmingham, Birmingham, AL, USA.
³² Center for Circadian and Sleep Medicine, Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
³³ Department of Biology, Stanford University and Sleep Research Society, Stanford, CA, USA.

PMID: 37224457
PMCID: PMC10485572
DOI: 10.1093/sleep/zsad069

Review

Beyond the symptom: the biology of fatigue

David M Raizen et al. Sleep. 2023.

. 2023 Sep 8;46(9):zsad069.

doi: 10.1093/sleep/zsad069.

Authors

Affiliations

¹ Department of Neurology, University of Pennsylvania, Philadelphia, PA, USA.
² Department of Neurology, Harvard Medical School, Boston, MA, USA.
³ Department of Neurological Surgery, University of California, Davis School of Medicine, Sacramento, CA, USA.
⁴ Department of Psychiatry and Neurobehavioural Science, and APC Microbiome Ireland, University College Cork, Cork, Ireland.
⁵ Brighton and Sussex Medical School Department of Neuroscience, University of Sussex, Brighton, UK.
⁶ Department of Symptom Research, Division of Internal Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁷ Department of Biochemistry and Genetics, Stanford University, Palo Alto, CA, USA.
⁸ Department of Chemistry and Biochemistry, Institute of Arctic Biology, Center for Transformative Research in Metabolism, University of Alaska Fairbanks, Fairbanks, AK, USA.
⁹ Division of Clinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA.
¹⁰ Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, CA, USA.
¹¹ Department of Psychology, Neuroscience Program, Smith College, Northampton, MA, USA.
¹² Center for Infection and Immunity, and Departments of Neurology and Pathology, Columbia University, New York City, NY, USA.
¹³ Division of Sleep Medicine, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
¹⁴ Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
¹⁵ Department of Clinical Immunology, College of Osteopathic Medicine, Nova Southeastern University, Ft. Lauderdale, FL, USA.
¹⁶ National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
¹⁷ Department of Neurology, NYU Grossman School of Medicine, NYC, NY, USA.
¹⁸ University College London, Queen Square Institute of Neurology, London, England.
¹⁹ Department of Psychology, Stockholm University, Stockholm, Sweden.
²⁰ Center for Systems Neuroscience, Department of Biomedical Engineering, Boston University, Boston, MA, USA.
²¹ Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology, Thuwal, Kingdom of Saudi Arabia.
²² Department of Physiological Nursing, School of Nursing, University of California, San Francisco, CA, USA.
²³ Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
²⁴ Departments of Neurology and Neurosurgery, University of Rochester Medical Center, Rochester, NY, USA.
²⁵ Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA.
²⁶ Department of Genetics, Institute for Biomedical Informatics, Penn Center for Precision Medicine, University of Pennsylvania, Philadelphia, PA, USA.
²⁷ Department of Neurobiology, Harvard University, Boston, MA, USA.
²⁸ Rappaport Institute for Medical Research, Technion, Israel Institute of Technology, Haifa, Israel.
²⁹ Department of Psychological Sciences, University of Connecticut, Storrs, CT, USA.
³⁰ Rocco Ortenzio Neuroimaging Center at Kessler Foundation, East Hanover, NJ, USA.
³¹ Department of Psychology, University of Alabama, Birmingham, Birmingham, AL, USA.
³² Center for Circadian and Sleep Medicine, Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
³³ Department of Biology, Stanford University and Sleep Research Society, Stanford, CA, USA.

PMID: 37224457
PMCID: PMC10485572
DOI: 10.1093/sleep/zsad069

Abstract

A workshop titled "Beyond the Symptom: The Biology of Fatigue" was held virtually September 27-28, 2021. It was jointly organized by the Sleep Research Society and the Neurobiology of Fatigue Working Group of the NIH Blueprint Neuroscience Research Program. For access to the presentations and video recordings, see: https://neuroscienceblueprint.nih.gov/about/event/beyond-symptom-biology-fatigue. The goals of this workshop were to bring together clinicians and scientists who use a variety of research approaches to understand fatigue in multiple conditions and to identify key gaps in our understanding of the biology of fatigue. This workshop summary distills key issues discussed in this workshop and provides a list of promising directions for future research on this topic. We do not attempt to provide a comprehensive review of the state of our understanding of fatigue, nor to provide a comprehensive reprise of the many excellent presentations. Rather, our goal is to highlight key advances and to focus on questions and future approaches to answering them.

Published by Oxford University Press on behalf of Sleep Research Society (SRS) 2023.

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References

1. Kuppuswamy A. The fatigue conundrum. Brain. 2017;140:2240–2245. doi:10.1093/brain/awx153. - DOI - PMC - PubMed
1. Krupp LB, et al. . The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol. 1989;46:1121–1123. doi:10.1001/archneur.1989.00520460115022. - DOI - PubMed
1. Kluger BM, et al. . Fatigue and fatigability in neurologic illnesses: proposal for a unified taxonomy. Neurology. 2013;80:409–416. doi:10.1212/WNL.0b013e31827f07be. - DOI - PMC - PubMed
1. Latourelle JC, et al. . Large-scale identification of clinical and genetic predictors of motor progression in patients with newly diagnosed Parkinson’s disease: a longitudinal cohort study and validation. Lancet Neurol. 2017;16(11):908–916. doi:10.1016/S1474-4422(17)30328-9. - DOI - PMC - PubMed
1. Kirby JC, et al. . PheKB: a catalog and workflow for creating electronic phenotype algorithms for transportability. J Am Med Infor Assoc. 2016;23(6):1046–1052. - PMC - PubMed

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Beyond the symptom: the biology of fatigue

Affiliations

Beyond the symptom: the biology of fatigue

Authors

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Abstract

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Medical