Association between baseline circulating FGF21 Levels and Depressive Symptoms at follow up in Older Adults: Evidence from the FRASNET Cohort

Rationale: to evaluate Fibroblast Growth Factor 21 (FGF21) as a possible biomarkers for depressive symtopms in elderly.
FGF21 is a stress-induced hepatokine involved in inflammation and neuroendocrine regulation, processes implicated in depression.
Methods: We investigated the association between FGF21 and depressive symptoms in community-dwelling older adults.
Data were obtained from 52 older individuals (median age 70; 61.5% women) within the FRASNET cohort who underwent longitudinal assessments (2017 for baseline –2024 for follow up). 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.