Immune-Metabolic Dysregulation and Suicide Risk in Adolescents with Major Depressive Disorder: A Cross- Sectional Study

Background: Biomarkers distinguishing suicidal from non-suicidal adolescents with major depressive disorder (MDD) remain elusive. This study investigated immune-metabolic dysregulation and its predictive utility for suicide attempt (SA) risk in medication-naïve adolescents. Methods: A case-control study compared 168 non-suicidal MDD adolescents with 96 MDD+SA adolescents (recent SA). Peripheral biomarkers included immune cell ratios (neutrophil/HDL [NHR], monocyte/HDL [MHR], lymphocyte/HDL [LHR]), metabolic markers (triglycerides, HDL-C, total protein (TP)), and hematological indices. Analyses employed group comparisons (t-tests/Mann-Whitney U), Spearman correlations, binary logistic regression, and ROC analysis. Results: The groups were well-matched demographically and for clinical severity. After adjusting for covariates, the MDD+SA group exhibited significant immune-metabolic dysregulation, including granulocyte hyperactivity, elevated inflammatory ratios, profound HDL-C depletion, hypertriglyceridemia, and reduced total protein (all key findings with adjusted p < 0.05). A post-hoc False Discovery Rate analysis confirmed the robustness of the core lipid findings. Binary logistic regression, adjusted for age, sex, and BMI, identified triglycerides (adjusted OR=2.17 per mmol/L) and total protein (adjusted OR=0.93 per g/L decrease) as independent predictors of SA. A model combining triglycerides and total protein significantly outperformed individual biomarkers in ROC analysis (AUC=0.74, 95% CI: 0.68-0.80). Conclusions: Convergent lipid-protein dysregulation represents a novel pathway for adolescent SA risk, identifiable as a significant shift within the normal laboratory range. A simple two-biomarker panel shows promise for risk stratification but requires future validation. These findings highlight metabolic dysfunction as a potential target for preventive strategies, though they do not yet constitute evidence for specific clinical interventions.