Serum S100B and Suicidal Ideation in Major Depressive Disorder: Evidence for a Trauma-Mediated Neurobiological Pathway

Serum S100B has been proposed as a peripheral biomarker associated with neuroinflammatory and astroglial stress-related processes in major depressive disorder (MDD). This study aimed to evaluate serum S100B levels in patients with MDD and suicidal ideation and to investigate whether childhood trauma mediates the relationship between suicide probability and S100B levels. This study included patients with MDD and suicidal ideation (n = 29), patients with MDD without suicidal ideation (n = 30), and healthy controls (n = 29). Serum S100B levels were measured before and after treatment in patients with suicidal ideation. Suicide Probability Scale (SPS), Childhood Trauma Questionnaire (CTQ), and Rosenberg Self-Esteem Scale (RSES) scores were assessed. Group comparisons were performed using Mann–Whitney U and Kruskal–Wallis tests with Dunn–Bonferroni post hoc analysis. Logistic regression and mediation analyses were conducted to examine the relationships among suicide probability, childhood trauma, and S100B levels. Pre-treatment serum S100B levels were significantly higher in patients with MDD and suicidal ideation compared with healthy controls (median 10.95 vs. 8.97 pg/mL, p = 0.001), whereas post-treatment levels did not differ between groups (median 7.84 vs. 8.97 pg/mL, p = 0.323). Within-group analysis demonstrated a significant reduction in S100B levels after treatment (Z = −3.359, p < 0.001). Additional three-group comparison revealed a significant overall difference in S100B levels among the study groups (H = 8.17, p = 0.017). Logistic regression analysis showed that serum S100B levels were independently associated with suicidal ideation (OR = 1.14, 95% CI 1.02–1.27, p = 0.021). Mediation analyses demonstrated a significant indirect effect of suicide probability on S100B levels through childhood trauma (Sobel Z = −2.45, p = 0.014). Serum S100B levels were elevated during the acute phase of MDD with suicidal ideation and decreased following treatment; however, the specificity of this longitudinal change to suicidality could not be determined within the present study design. The relationship between suicide probability and S100B levels appears to be mediated by childhood trauma, suggesting that S100B may reflect trauma-related neurobiological vulnerability rather than a disease-specific biomarker of suicidality. These findings support a potential association between peripheral glial-related biomarkers and stress-responsive neurobiological processes underlying suicidality.