Association between baseline circulating FGF21 levels and depressive symptoms at follow up in older adults: evidence from the FRASNET cohort

Objectives Fibroblast Growth Factor 21 (FGF21) is a stress-induced hepatokine involved in inflammation and neuroendocrine regulation, processes implicated in depression. We investigated the association between FGF21 and depressive symptoms in community-dwelling older adults.Methods Data were obtained from 52 older individuals (median age 70; 61.5% women) within the FRASNET cohort who underwent longitudinal assessments (2017-2024). Depressive symptoms were evaluated using the 15-item Geriatric Depression Scale (GDS). Regression models adjusted for age, sex, and body mass index were used to assess associations between FGF21 and depressive symptoms.Results Circulating FGF21 levels declined significantly over time (p = 0.03) but remained higher in individuals with depressive symptoms at both baseline and follow-up. Elevated baseline FGF21 predicted higher GDS scores at follow-up (adjusted B = 0.003, 95% CI 0.000-0.006, p = 0.049). Discriminatory performance for elevated depressive symptoms was modest (AUC = 0.66).Conclusions Higher baseline FGF21 levels were associated with greater depressive symptom burden at follow-up. These findings should be considered preliminary and hypothesis-generating. Further studies using diagnostic outcomes and larger samples are warranted.