Composite Inflammatory Burden and Suicide Risk: The Predictive Role of SII, SIRI, and PIV in Patients with Major Depressive Disorder

Abstract Background Major depressive disorder (MDD) is a leading cause of disability worldwide and strongly associated with suicidal behavior. Identifying accessible biological markers for suicide risk in MDD remains a critical clinical need. Recent studies suggest that systemic inflammatory indices may play a role in suicidal behavior. Objective This study aimed to investigate whether novel hematological inflammatory markers—Systemic Immune-Inflammation Index (SII), Systemic Inflammation Response Index (SIRI), and Pan-Immune-Inflammation Value (PIV)—may predict suicide attempts in patients with MDD. Methods A total of 204 patients with MDD were categorized into two groups: those with a history of suicide attempt (SA; n = 104) and those without (NSA; n = 100). Hematologic parameters and inflammatory indices (SII, SIRI, PIV) were compared between groups. Principal component analysis (PCA) was applied to these indices to create a Composite Inflammatory Index (CII). Multivariate logistic regression analysis was conducted to identify predictors of suicide attempt. Results SA patients had significantly higher levels of SII, SIRI ( p < .001 for both), and PIV ( p = .002) compared to NSA patients. PCA revealed strong positive loadings for SII, SIRI, and PIV on a single component (explaining 91.4% of variance). Logistic regression analysis demonstrated that younger age ( p = .03), lower platelet count ( p = .018), and higher CII ( p < .001) were independent predictors of suicide attempt (AUC = 0.748). Conclusion Elevated systemic inflammatory indices, particularly when combined into a composite factor, are strong predictors of suicide attempts in MDD patients. These easily accessible, low-cost biomarkers may enhance clinical risk assessment and guide early preventive strategies. Further prospective studies are warranted to validate these findings.