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<p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2024-03-05T00:00:00-05:00" class="date-display-single">March 5, 2024</span></p><div class='syndicate'><h1>Insight into mechanisms of ME/CFS</h1><div class="callout callout-with-border"><h3>At a Glance</h3>
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<li>Researchers compared people with post-infectious ME/CFS to those without and found important differences in their brains and other body systems.</li>
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<li>The findings suggest potential mechanisms for ME/CFS, as well as possible therapeutic targets.</li>
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</ul></div><div class="media-float-right"><div class="ds-1col file file-image file-image-jpeg view-mode-floated_media clearfix">
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<picture title="A medical technician watches the monitor of a woman with IVs in a hospital bed.">
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-large/public/news-events/research-matters/2024/20240305-mecfs-patient.jpeg?itok=Xw-Ar_to&timestamp=1709661095 1x" media="screen and (min-width: 960px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2024/20240305-mecfs-patient.jpeg?itok=Q8Md09LT&timestamp=1709661095 1x" media="screen and (min-width: 800px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium-small/public/news-events/research-matters/2024/20240305-mecfs-patient.jpeg?itok=sdN3p7SB&timestamp=1709661095 1x" media="screen and (min-width: 600px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-small/public/news-events/research-matters/2024/20240305-mecfs-patient.jpeg?itok=g3uiHU5e&timestamp=1709661095 1x" media="screen and (min-width: 480px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-tiny/public/news-events/research-matters/2024/20240305-mecfs-patient.jpeg?itok=20q3FrJg&timestamp=1709661095 1x" media="screen and (min-width: 0)" />
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<!--[if IE 9]></video><![endif]-->
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<img src="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2024/20240305-mecfs-patient.jpeg?itok=Q8Md09LT&timestamp=1709661095" alt="A medical technician watches the monitor of a woman with IVs in a hospital bed." title="A medical technician watches the monitor of a woman with IVs in a hospital bed." />
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</picture><span class="caption">A participant in the ME/CFS study at NIH’s Clinical Center. </span><span class="credit">Alison Sbrana</span></div>
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</div><p>Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) involves debilitating fatigue, intolerance to exercise, and cognitive problems. Symptoms tend to get worse after even mild exertion. The cause remains unknown, hampering development of treatments. ME/CFS often develops after an infection—a condition known as post-infectious-ME/CFS (PI-ME/CFS).</p>
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||
|
||
<p>A research team led by NIH’s Dr. Avindra Nath conducted an in-depth study of 17 people with PI-ME/CFS and 21 healthy volunteers. Their aim was to uncover key features that might be driving PI-ME/CFS. Results appeared in <em>Nature Communications </em>on February 21, 2024.</p>
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||
|
||
<p>People with PI-ME/CFS had higher heart rates throughout the day and a smaller drop in their nighttime heart rate than healthy volunteers. This suggests that the autonomic nervous system, which controls unconscious bodily functions, is disrupted in PI-ME/CFS. Heart and lung function were also less able to respond to exercise in people with PI-ME/CFS.</p>
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||
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||
<p>In one test, participants were repeatedly given the choice of performing either an easy task for a low reward or a hard task for a higher reward. Those with PI-ME/CFS were less likely to choose the hard task than the healthy volunteers, suggesting less ability to exert effort. The healthy volunteers had reduced muscle function and brain motor cortex activity after repeated tasks. But people with PI-ME/CFS did not. Brain scans during one task found that those with PI-ME/CFS had lower activity in a brain region called the temporoparietal junction. These findings suggest that the fatigue of those with PI-ME/CFS might be caused by dysfunction in the way the brain decides how to exert effort.</p>
|
||
|
||
<p>When the team analyzed cerebrospinal fluid, they found that participants with PI-ME/CFS had reduced levels of chemicals called catechols. Catechols help regulate the nervous system. Catechol levels correlated with effort preference and motor function in people with PI-ME/CFS, but not in healthy volunteers. This suggests that altered catechol signaling in the brains of people with PI-ME/CFS may give rise to their altered effort.</p>
|
||
|
||
<p>The team examined immune function as well. They found differences in B cells, which make antibodies to help fight pathogens. People with PI-ME/CFS had more naïve B cells, which can be activated by any foreign substance. But they had fewer switched memory B cells, which respond to a specific pathogen that the body has encountered before. B cell dysfunction was more prominent in women. These findings suggests that the immune system continues to be activated in the absence of infection.</p>
|
||
|
||
<p>Taken together, the results suggest that PI-ME/CFS may be caused by immune system dysfunction that is triggered by infections. This may lead to chemical changes in the central nervous system that affect certain brain functions to cause ME/CFS symptoms.</p>
|
||
|
||
<p>“Rather than physical exhaustion or a lack of motivation,” says first author Dr. Brian Walitt, “fatigue may arise from a mismatch between what someone thinks they can achieve and what their bodies perform.”</p>
|
||
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||
<p>“Men and women were quite divergent in their data,” Nath notes, “and that tells you that ME/CFS is not one-size-fits-all. Considering male and female immune differences in ME/CFS, the results may open up new avenues of research that could provide insight into other infection-associated chronic diseases.”</p>
|
||
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<p>The findings also suggest ways in which PI-ME/CFS might be treated, either by targeting the immune system or specific circuits in the brain.</p>
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<p>—by Brian Doctrow, Ph.D.</p></div><h2 class="label-above">Related Links</h2><ul class="spaced print-urls"><li><a href="https://www.nih.gov/news-events/nih-research-matters/protein-may-be-linked-exercise-intolerance-me-cfs" target="_top">Protein May Be Linked to Exercise Intolerance In ME/CFS</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/immune-cell-metabolism-altered-me-cfs" target="_top">Immune Cell Metabolism Altered in ME/CFS</a></li><li><a href="https://directorsblog.nih.gov/2023/02/14/more-clues-into-me-cfs-discovered-in-gut-microbiome/" target="_top">More Clues into ME/CFS Discovered in Gut Microbiome</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/blood-test-may-detect-myalgic-encephalomyelitis/chronic-fatigue-syndrome" target="_top">Blood Test May Detect Myalgic Encephalomyelitis/Chronic Fatigue Syndrome</a></li><li><a href="https://newsinhealth.nih.gov/2022/11/feeling-fatigued" target="_top">Feeling Fatigued?</a></li><li><a href="https://www.nih.gov/mecfs" target="_top">Advancing ME/CFS Research</a></li><li><a href="https://www.cdc.gov/me-cfs/index.html" target="_top">Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (CDC)</a></li></ul><p class="footnote"><strong class="label-inline">References: </strong><a href="https://pubmed.ncbi.nlm.nih.gov/38383456/">Deep phenotyping of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome.</a> Walitt B, Singh K, LaMunion SR, Hallett M, Jacobson S, Chen K, Enose-Akahata Y, Apps R, Barb JJ, Bedard P, Brychta RJ, Buckley AW, Burbelo PD, Calco B, Cathay B, Chen L, Chigurupati S, Chen J, Cheung F, Chin LMK, Coleman BW, Courville AB, Deming MS, Drinkard B, Feng LR, Ferrucci L, Gabel SA, Gavin A, Goldstein DS, Hassanzadeh S, Horan SC, Horovitz SG, Johnson KR, Govan AJ, Knutson KM, Kreskow JD, Levin M, Lyons JJ, Madian N, Malik N, Mammen AL, McCulloch JA, McGurrin PM, Milner JD, Moaddel R, Mueller GA, Mukherjee A, Muñoz-Braceras S, Norato G, Pak K, Pinal-Fernandez I, Popa T, Reoma LB, Sack MN, Safavi F, Saligan LN, Sellers BA, Sinclair S, Smith B, Snow J, Solin S, Stussman BJ, Trinchieri G, Turner SA, Vetter CS, Vial F, Vizioli C, Williams A, Yang SB; Center for Human Immunology, Autoimmunity, and Inflammation (CHI) Consortium; Nath A. <em>Nat Commun.</em> 2024 Feb 21;15(1):907. DOI: 10.1038/s41467-024-45107-3. PMID: 38383456</p><p class="footnote"><strong class="label-inline">Funding: </strong>NIH’s National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Mental Health (NIMH), National Heart, Lung, and Blood Institute (NHLBI), National Institute of Diabetes and Digestive and Kidney Disease (NIDDK), National Institute of Environmental Health Sciences (NIEHS), National Institute of Allergy and Infectious Diseases (NIAID), Clinical Center (CC), National Institute of Dental and Craniofacial Research (NIDCR), National Institute on Drug Abuse (NIDA), National Institute on Aging (NIA), National Institute of Nursing Research (NINR), National Center for Complementary and Integrative Health (NCCIH), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and National Cancer Institute (NCI).</p>
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