{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T09:35:48Z","timestamp":1768296948226,"version":"3.49.0"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T00:00:00Z","timestamp":1747785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Johann Wolfgang Goethe-Universit\u00e4t, Frankfurt am Main"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>In clinical routine, it might be difficult to distinguish between fatigue and depression in Multiple sclerosis (MS). We investigated in two independent observational cohort studies which clinical and paraclinical features distinguish patients reporting fatigue but no depressive symptoms from those suffering from depressive symptoms but having no relevant fatigue. In Study 1, <jats:italic>n<\/jats:italic>\u2009=\u2009156 MS patients underwent fatigue, depression, cognitive screening and flow cytometry measurements. In Study 2, <jats:italic>n<\/jats:italic>\u2009=\u200954 MS patients performed a comprehensive neuropsychological evaluation. Patients reporting predominantly fatigue symptoms were older, had a lower information processing speed and higher EDSS compared to those scoring high on depression. CD3\u2009+\u2009CD4\u2009+\u2009T-helper cells count distinguished patients with depressive symptoms from those with neither depression nor fatigue. Study 2 demonstrated similar results. Additionally, progressive MS was associated with fatigue. From the whole neuropsychological test battery only SDMT distinguished fatigue from depressive phenotypes with the latter performing better. In both studies the groups did not differ regarding any other baseline variable including disease activity. Older age, slow information processing, worse physical disability and progressive disease course are distinguishing features of patients reporting more fatigue than depressive symptoms. Higher peripheral inflammatory cell counts seem to characterize depression.<\/jats:p>","DOI":"10.1038\/s41598-025-03079-4","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T21:06:12Z","timestamp":1747861572000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Clinical and paraclinical features distinguish fatigue from depression-predominant phenotypes in multiple sclerosis"],"prefix":"10.1038","volume":"15","author":[{"given":"Yavor","family":"Yalachkov","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberly","family":"Koerbel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Gehrig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marion","family":"Hug","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iris-Katharina","family":"Penner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Maiworm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,5,21]]},"reference":[{"key":"3079_CR1","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1186\/s12883-021-02396-1","volume":"21","author":"A Oliva Ramirez","year":"2021","unstructured":"Oliva Ramirez, A. et al. Prevalence and burden of multiple sclerosis-related fatigue: A systematic literature review. BMC Neurol. 21, 468. https:\/\/doi.org\/10.1186\/s12883-021-02396-1 (2021).","journal-title":"BMC Neurol."},{"key":"3079_CR2","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1177\/1352458511417835","volume":"17","author":"A Feinstein","year":"2011","unstructured":"Feinstein, A. Multiple sclerosis and depression. Mult Scler. 17, 1276\u20131281. https:\/\/doi.org\/10.1177\/1352458511417835 (2011).","journal-title":"Mult Scler."},{"key":"3079_CR3","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.msard.2019.01.049","volume":"30","author":"Y Yalachkov","year":"2019","unstructured":"Yalachkov, Y. et al. Determinants of quality of life in relapsing\u2013remitting and progressive multiple sclerosis. Mult. Scler. Relat. Disord. 30, 33\u201337. https:\/\/doi.org\/10.1016\/j.msard.2019.01.049 (2019).","journal-title":"Mult. Scler. Relat. 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No association between disease modifying treatment and fatigue in multiple sclerosis. Mult. Scler. Relat. Disord. 79, 104993. https:\/\/doi.org\/10.1016\/j.msard.2023.104993 (2023).","journal-title":"Mult. Scler. Relat. Disord."},{"key":"3079_CR9","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-023-12021-5","author":"D Ontaneda","year":"2023","unstructured":"Ontaneda, D. et al. Identification and management of subclinical disease activity in early multiple sclerosis: A review. J. Neurol. https:\/\/doi.org\/10.1007\/s00415-023-12021-5 (2023).","journal-title":"J. Neurol."},{"key":"3079_CR10","doi-asserted-by":"publisher","first-page":"817256","DOI":"10.3389\/fneur.2021.817256","volume":"12","author":"J Tarasiuk","year":"2021","unstructured":"Tarasiuk, J. et al. Co-occurrence of fatigue and depression in people with multiple sclerosis: A Mini-Review. Front. Neurol. 12, 817256. https:\/\/doi.org\/10.3389\/fneur.2021.817256 (2021).","journal-title":"Front. 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Kimberly Koerbel is a participantat the Junior Clinician Scientist Program funded by Goethe University Frankfurt and receivedspeaker honoraria by Novartis. Johannes Gehrig has been supported by a travel grant fromSanofi. Marion Hug reports no conflicts of interest. Iris\u2010Katharina Penner has receivedhonoraria for speaking at scientific meetings, serving at scientific advisory boards andconsulting activities from Adamas Pharma, Almirall, Bayer Pharma, Biogen, BMS, Celgene, Sanofi\u2010Genzyme, Janssen, Merck Serono GmbH (an affiliate of Merck KGaA), Novartis, Roche and Teva; she has received research support from the German MS Society, Celgene, Roche, Teva and Novartis. Michelle Maiworm received speaking honoraria from Roche, Synlab and Novartis; her research was funded by the Faculty of Medicine at the GoetheUniversity Frankfurt and the Goethe Research Academy for Early Career Researchers (GRADE) of the Goethe University Frankfurt, the Heinrich und Erna Schaufler-Foundation aswell as the MS Foundation of the State of Hesse.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"17718"}}