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Research highlights autonomic dysfunction compared to healthy individuals, particularly involving the sympathetic branch. While past reviews focused on neurophysiological assessments, this systematic review summarises biological adrenergic markers, offering deeper insights into the observed sympathetic dysfunction in ME\/CFS and FM aiming to identify targetable pathophysiological mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A systematic search was performed on PubMed, Web of Science, Embase and Scopus. Studies investigating peripheral biological markers of adrenergic function in patients with ME\/CFS or FM compared to healthy controls at baseline were included. Meta\u2010analyses were performed using R statistical software.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>This meta\u2010analysis of 37 studies, encompassing 543 ME\/CFS patients and 651 FM patients, compared with 747 and 447 healthy controls, respectively, revealed elevated adrenaline (SMD\u2009=\u2009.49 [.31\u2013.67]; <jats:italic>Z<\/jats:italic>\u2009=\u20095.29, <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.01) and \u03b21 adrenergic receptor expression (SMD\u2009=\u2009.79 [.06\u20131.52]; <jats:italic>Z<\/jats:italic>\u2009=\u20092.13; <jats:italic>p<\/jats:italic>\u2009=\u2009.03) in blood of ME\/CFS patients at rest. Additionally, patients with ME\/CFS had a greater increase in the expression of \u03b12A adrenergic receptor (AR, SMD\u2009=\u2009.57 [.18\u2013.97]; <jats:italic>Z<\/jats:italic>\u2009=\u20092.85, <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.01), \u03b22 AR (SMD\u2009=\u2009.41 [.02\u2013.81]; <jats:italic>Z<\/jats:italic>\u2009=\u20092.04; <jats:italic>p<\/jats:italic>\u2009=\u2009.04) and COMT (SMD\u2009=\u2009.42 [.03\u2013.81]; <jats:italic>Z<\/jats:italic>\u2009=\u20092.11; <jats:italic>p<\/jats:italic>\u2009=\u2009.03) after exercise and an increased response of noradrenaline to an orthostatic test (SMD\u2009=\u2009.11 [\u2212.47 to \u2212.70]; <jats:italic>Z<\/jats:italic>\u2009=\u20092.10; <jats:italic>p<\/jats:italic>\u2009=\u2009.04), both found in blood. FM patients showed no significant differences at baseline but exhibited a diminished adrenaline response to exercise (SMD\u2009=\u2009\u2212.79 [\u22121.27 to \u2212.30]; <jats:italic>Z<\/jats:italic>\u2009=\u2009\u22123.14; <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.01).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This systematic review and meta\u2010analysis revealed adrenergic dysfunction mainly in patients with ME\/CFS. Higher baseline adrenaline levels and atypical responses to exercise in ME\/CFS indicate that sympathetic dysfunction, underscored by adrenergic abnormalities, is more involved in the pathophysiology of ME\/CFS rather than FM.<\/jats:p><\/jats:sec>","DOI":"10.1111\/eci.14318","type":"journal-article","created":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T15:44:33Z","timestamp":1727279073000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Adrenergic dysfunction in patients with myalgic encephalomyelitis\/chronic fatigue syndrome and fibromyalgia: A systematic review and meta\u2010analysis"],"prefix":"10.1111","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6375-5636","authenticated-orcid":false,"given":"Jolien","family":"Hendrix","sequence":"first","affiliation":[{"name":"Pain in Motion (PiM) international research group, Department of Physiotherapy, Human Physiology and Anatomy, Faculty of 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