Abstract
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 ± 275.87 pg/mL vs. 403.34 ± 173.29 pg/mL, p < 0.001, Mann–Whitney U test). A strong correlation between increasing age and higher GDF-15 levels was identified (p < 0.001, 95%-CI elevation of GDF-15 per year 5.246–10.850 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–Whitney 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.
Highlights
This study investigated whether serum concentrations of both Fibroblast-growth-factor 21 (FGF-21) and Growth-differentiation-factor 15 (GDF-15) are altered in patients suffering migraine considering disease severity, attack morphology and concomitant disorders
The GDF-15 values of four participants of the control group and two patients from the migraine group were excluded from the statistical analysis as they could not be determined precisely due to technical problems
This study investigated the association between serum concentrations of the biomarkers FGF-21 and GDF-15, which have been investigated for mitochondrial diseases, and the presence of migraine
Summary
As migraine prevalence is approximately three times higher in women than in man, a possible mitochondrial involvement in the pathophysiology of migraine has been discussed for many years In this context, biochemical analyses in patients with migraine showed significantly elevated lactate levels in serum and liquor pointing towards a disturbance in the oxidative metabolism [2,3]. The consequent hypoxia/ischemia, altered glutamate metabolism, and ionic homeostasis may trigger cortical spreading depolarization (CSD), which may activate the trigemino-vascular system leading to headache [10] It is unclear which signaling molecules are exactly involved in these processes. This study investigated whether serum concentrations of both FGF-21 and GDF-15 are altered in patients suffering migraine considering disease severity, attack morphology and concomitant disorders
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