{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T14:50:35Z","timestamp":1787755835107,"version":"build-2784847793"},"reference-count":46,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,18]],"date-time":"2021-09-18T00:00:00Z","timestamp":1631923200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Mitochondrial processes may play a role in the pathophysiology of migraine. Serum levels of two biomarkers, Fibroblast-growth-factor 21 (FGF-21) and Growth-differentiation-factor 15 (GDF-15), are typically elevated in patients with mitochondrial disorders. The study investigated whether the presence of migraine may influence FGF-21 and GDF-15 serum levels considering vascular and metabolic disorders as possible confounders. A cross-sectional study in two headache centers was conducted analyzing GDF-15 and FGF-21 serum concentration in 230 patients with episodic and chronic migraine compared to a control group. Key clinical features of headache were evaluated, as well as health-related life quality, anxiety and depression using SF-12 and HADS-questionnaires. Elevated GDF-15 values were detected in the migraine group compared to the control group (506.65 \u00b1 275.87 pg\/mL vs. 403.34 \u00b1 173.29 pg\/mL, p &lt; 0.001, Mann\u2013Whitney U test). A strong correlation between increasing age and higher GDF-15 levels was identified (p &lt; 0.001, 95%-CI elevation of GDF-15 per year 5.246\u201310.850 pg\/mL, multiple linear regression). Mean age was different between the groups, and this represents a confounding factor of the measurements. FGF-21 levels did not differ between migraine patients and controls (p = 0.635, Mann\u2013Whitney U test) but were significantly influenced by increasing BMI (p = 0.030, multiple linear regression). Neither biomarker showed correlation with headache frequency. Higher FGF-21 levels were associated with a higher mean intensity of headache attacks, reduced health-related life quality and anxiety. When confounding factors were considered, increased serum levels of FGF-21 and GDF-15 were not detected in migraine patients. However, the results show an age-dependence of GDF-15 in migraine patients, and this should be considered in future studies. Similar findings apply to the relationship between FGF-21 and BMI. Previous studies that did not adjust for these factors should be interpreted with caution.<\/jats:p>","DOI":"10.3390\/cells10092471","type":"journal-article","created":{"date-parts":[[2021,9,20]],"date-time":"2021-09-20T07:52:14Z","timestamp":1632124334000},"page":"2471","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The Mitochondrial Biomarkers FGF-21 and GDF-15 in Patients with Episodic and Chronic Migraine"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5730-0731","authenticated-orcid":false,"given":"Philipp","family":"Burow","sequence":"first","affiliation":[{"name":"Department of Neurology, University Hospital Halle-Saale, Ernst-Grube-Stra\u00dfe 40, 06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8845-9235","authenticated-orcid":false,"given":"Marc","family":"Haselier","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital Halle-Saale, Ernst-Grube-Stra\u00dfe 40, 06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1727-9362","authenticated-orcid":false,"given":"Steffen","family":"Naegel","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital Halle-Saale, Ernst-Grube-Stra\u00dfe 40, 06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leila Motlagh","family":"Scholle","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital Halle-Saale, Ernst-Grube-Stra\u00dfe 40, 06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charly","family":"Gaul","sequence":"additional","affiliation":[{"name":"Headache Center Frankfurt, Dalbergstra\u00dfe 2A, 65929 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten","family":"Kraya","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital Halle-Saale, Ernst-Grube-Stra\u00dfe 40, 06120 Halle (Saale), Germany"},{"name":"Department of Neurology, Hospital Sankt Georg, Delitzscher Stra\u00dfe 141, 04129 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1152\/physrev.00034.2015","article-title":"Pathophysiology of Migraine: A Disorder of Sensory Processing","volume":"97","author":"Goadsby","year":"2017","journal-title":"Physiol. 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