Transdiagnostic determinants of Growth Differentiation Factor-15 (GDF-15) in psychiatric in-patients: age, renal indices, interleukin-6 (IL-6) and soluble urokinase plasminogen activator receptor (suPAR).

Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine implicated in systemic inflammatory and renal stress biology. It remains unclear whether GDF-15 reflects diagnosis-specific biology or transdiagnostic physiological burden at acute psychiatric admission. In this cross-sectional study, 190 acutely admitted in-patients with schizophrenia spectrum disorders (SSD, n = 126) or mood disorders (MD, n = 64) underwent blood sampling within 12 h of emergency presentation. Serum GDF-15, interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), and soluble urokinase plasminogen activator receptor (suPAR) were assayed, alongside creatinine, urea, and estimated glomerular filtration rate (eGFR). Group comparisons were conducted using independent-samples t-tests or Mann-Whitney U tests for continuous variables and χ2 or Fisher's exact tests for categorical variables. Following Bonferroni correction across 31 comparisons (p < 1.6 × 10-3), antidepressant burden and previous hospitalizations were the only significant between-group differences. GDF-15 showed a non-significant trend towards higher values in MD than SSD patients. In the primary complete-case multivariable model, diagnostic category was not independently associated with ln (GDF-15) after adjustment for age, urea, ln (IL-6), and ln (suPAR) (MD vs SSD: B = -0.012, β = -0.010, p = 0.900). Instead, ln (GDF-15) was associated with older age (B = 0.013, p = 3.0 × 10-4), higher urea (B = 0.010, p = 0.027), higher ln (IL-6) (B = 0.167, p = 2.4 × 10-4), and higher ln (suPAR) (B = 0.297, p = 0.001), explaining 40.2% of variance. Sensitivity analyses adjusting for smoking, cardiovascular disease, thyroid disorder, sex, and alternative diagnostic classification did not materially alter the absence of a diagnostic-group effect. In conclusion, GDF-15 variation was better explained by transdiagnostic renal-immune a stress phenotype than by categorical diagnosis, supporting its evaluation as a marker of systemic physiological burden rather than a diagnosis-specific biomarker.