C-reactive protein predicts aggression in adolescent depression: Non-suicidal self-injury moderation and immunomodulatory shift.

Major depressive disorder (MDD) in adolescents is frequently accompanied by aggression and non-suicidal self-injury (NSSI), yet reliable biomarkers for predicting these behavioral risks remain limited. This study employed a combined cross-sectional and longitudinal design to investigate the role of peripheral inflammatory markers in aggression among 214 adolescent inpatients with MDD and 60 healthy controls. We found that C-reactive protein (CRP) emerged as notable independent predictor of aggressive behavior, showing a high area under the curve (AUC=0.91) in this sample, suggesting its potential discriminatory performance that warrants further validation. Notably, NSSI significantly moderated the CRP-aggression link, with a stronger association observed in patients without NSSI. Furthermore, sex-specific IL-6 elevations were identified in female NSSI⁺ patients. Longitudinal analyses revealed a dynamic "immunomodulatory shift," where systemic immune-inflammation index (SII) and lymphocyte-to-monocyte ratio (LMR) transitioned from positive to negative predictors of aggression over time. These preliminary findings highlight the potential of CRP as a clinically accessible indicator for aggression risk and underscore the temporal complexity of immune-behavior interactions in adolescent depression. These preliminary findings remain to be verified through independent cohorts in future studies.