Circulating Growth Differentiation Factor-15 (GDF-15) levels in depressive disorders - A systematic review and meta-analysis of the association between GDF-15 and depression in adult populations.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of observational studies
PubMed 42049068 · doi:10.1016/j.jad.2026.121837
What was done
A systematic review and meta-analysis evaluated the association between blood Growth Differentiation Factor-15 (GDF-15) levels and depression in adults. Observational studies using standardized depression criteria and laboratory blood measurements were identified, and quality was appraised using the Newcastle-Ottawa Scale. Thirteen studies comprising 55,985 total participants (4,997 with depression) across general, late-life, post-stroke, and male-only cohorts were reviewed, with a subset quantitatively pooled.
What was found
Twelve of the 13 included studies reported elevated GDF-15 levels in depressed individuals. Meta-analysis of six studies (n = 5,657) revealed significantly higher circulating GDF-15 in individuals with depression compared to controls (standardized mean difference [SMD] = 0.39, 95% CI: 0.19 to 0.58; p = 0.0039). Heterogeneity was moderate to high (I² = 68.7%), but dropped substantially after excluding one study. Correlations between GDF-15 levels and depression severity were inconsistent across studies.
Why it matters
This review supports GDF-15 as a potential circulating biomarker of inflammation and cellular stress in depressive disorders.
Limits
All included studies were observational, preventing causal inference. Only 6 of 13 studies had data suitable for meta-analysis. Substantial clinical and methodological heterogeneity existed across patient populations (e.g., stroke vs. general adult), GDF-15 assay methods, and depression diagnostic tools.
Cited by
- supports Lactate and GDF15 levels tend to be elevated in individuals with mental illness.