Age-dependent associations between growth differentiation factor 15 (GDF-15) and depressive symptoms: Evidence from a population-based cohort

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Growth differentiation factor 15 (GDF-15) is a protein that is upregulated with aging, inflammation, and various somatic diseases. Emerging evidence suggests that GDF-15 may also be associated with depression and anxiety. The study examined cross-sectional and longitudinal associations between GDF-15 and symptoms of depression and anxiety in a population-based sample. Severity of depressive ( n = 624; 55.8% male; 56.8 ± 15.8 years, 20.1–79.6 years) and anxiety ( n = 261; 55.2% male; 56.4 ± 16.7 years, 20.5–78.6 years) symptoms were measured using the CES-D and GAD-7 at baseline and follow-up (mean interval 6.3 years ±5.7 months). GDF-15 levels were measured once at baseline from fasting blood samples using an electrochemiluminescence immunoassay. Multiple regression models revealed a significant negative association between GDF-15 levels and depressive symptoms at both baseline ( p = .032, Adjusted R 2 = 0.279) and follow-up ( p = .040, Adjusted R 2 = 0.293). At both time points, this relationship was moderated by age, as indicated by a significant GDF-15 x age interaction ( p = .019 at baseline; p = .030 at follow-up). Older participants showed a significant positive association between GDF-15 and depressive symptoms at both baseline (≥ 71.66 years, p = .050) and follow-up (≥ 73.51 years, p = .050), whereas no association was identified in younger adults. No significant association emerged between GDF-15 levels and anxiety symptoms. These findings suggest age-dependent associations between GDF-15 and depressive symptomatology and highlight the importance of considering age as a moderator in biomarker research on mental health.

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