{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:16:10Z","timestamp":1787008570362,"version":"build-2736575974"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"3","funder":[{"DOI":"10.13039\/100030692","name":"Intramural Research Program of the National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100030692","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Intramural Research Projects","award":["NS003157"],"award-info":[{"award-number":["NS003157"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Fatigue, brain fog and post-exertional malaise are major features of post-infectious myalgic encephalomyelitis\/chronic fatigue syndrome and post-acute sequelae of severe acute respiratory syndrome coronavirus 2. To date, no specific neurotransmitter abnormalities have been found in either condition. We examined the possibility of central catecholaminergic involvement and clinical correlates in post-infectious myalgic encephalomyelitis\/chronic fatigue syndrome and post-acute sequelae of severe acute respiratory syndrome coronavirus 2 groups compared to healthy volunteers and, as positive controls, Parkinson\u2019s disease patients. In an observational, cross-sectional cohort study conducted at the National Institutes of Health Clinical Center we measured CSF levels of catecholamines and metabolites in the four groups and assessed correlations with neurobehavioral measures. CSF indices of the central Norepinephrine Pathway (norepinephrine + 3,4-dihydroxyphenylglycol + 3-methoxy-4-hydroxyphenylglycol) and Dopamine Pathway (dopamine + 3,4-dihydroxyphenylacetic acid + homovanillic acid) were measured and related to patient-recorded outcomes and physiological assessments. Mean values for Norepinephrine Pathway activity (in pmol\/mL) were lower in the post-infectious myalgic encephalomyelitis\/chronic fatigue syndrome, post-acute sequelae of severe acute respiratory syndrome coronavirus 2, and Parkinson\u2019s disease groups compared to the healthy volunteer cohort (post-infectious myalgic encephalomyelitis\/chronic fatigue syndrome (\u221215.9, 95% confidence interval [\u221226.1, \u22125.7], P = 0.0006); post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (\u22129.62, [\u221217.9, \u22121.4], P = 0.015); Parkinson\u2019s disease (\u221219.4, [\u221227.5, \u221211.3], P &amp;lt; 0.0001)). Post-acute sequelae of severe acute respiratory syndrome coronavirus 2 participants with post-exertional malaise had evidence of central noradrenergic deficiency compared to healthy volunteers (\u221218.3 [\u221231.3, \u22125.3], P = 0.0018). The post-infectious myalgic encephalomyelitis\/chronic fatigue syndrome and post-acute sequelae of severe acute respiratory syndrome coronavirus 2 groups did not differ from the healthy group in values for the Dopamine Pathway index. Across all participants, Norepinephrine Pathway activity correlated positively with handgrip duration and general health and negatively with fatigue. We conclude that post-infectious myalgic encephalomyelitis\/chronic fatigue syndrome and post-acute sequelae of severe acute respiratory syndrome coronavirus 2 feature a specific central neurotransmitter pattern involving noradrenergic but not dopaminergic deficiency. The noradrenergic abnormality is associated with major symptoms such as post-exertional malaise.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag173","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T12:08:14Z","timestamp":1778674094000},"source":"Crossref","is-referenced-by-count":1,"title":["Central noradrenergic deficiency in post-infectious chronic fatigue: neurobehavioral correlates"],"prefix":"10.1093","volume":"8","author":[{"given":"Lillian","family":"Aregawi","sequence":"first","affiliation":[{"name":"Office of the Clinical Director, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Walitt","sequence":"additional","affiliation":[{"name":"Office of the Clinical Director, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patti","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina","family":"Norato","sequence":"additional","affiliation":[{"name":"Clinical Trials Unit, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohit Ninan","family":"Benjamin","sequence":"additional","affiliation":[{"name":"Office of the Clinical Director, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5709-9940","authenticated-orcid":false,"given":"David S","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, MD 20892 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"2026052605135222300_fcag173-B1","doi-asserted-by":"crossref","DOI":"10.1186\/1476-5918-7-6","article-title":"The economic impact of ME\/CFS: Individual and societal costs","volume":"7","author":"Jason","year":"2008","journal-title":"Dyn 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