Serum HMGB1 as a Diagnostic Biomarker and Mediator of Childhood Trauma in Adolescent Depression

Jingyue Xiang^1,2Yiqun Qin³Ruhong Jiang^2,4Xiaolan Wang^2,4Yang Zhou^2,4Jia Liu^2,4Li Kuang^2*

• ¹Department of Psychiatry, First Affiliated Hospital of Chongqing Medical University, Chongqing, China
• ²Psychiatric Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
• ³First Clinical Medical College, Chongqing Medical University, Chongqing, Chongqing, China
• ⁴Mental Health Center, University-Town Hospital of Chongqing Medical University, Chongqing, China

Background: Adolescent depression is a global health challenge with increasing rates and long-term impacts on development. Current diagnostics lack objective biomarkers, relying on subjective assessments. Neuroinflammation, particularly High mobility group box 1 (HMGB1), a systemic inflammation mediator, is implicated in adult depression but not well-studied in adolescents. Childhood trauma, a risk factor for neuroinflammatory dysregulation, has been linked to increased inflammatory markers but not specifically to HMGB1. This study explores serum HMGB1 as a diagnostic biomarker for adolescent depression and its role in exacerbating symptoms through childhood trauma. Methods: 160 participants, including 80 depressive adolescents and 80 healthy controls, were enrolled. The depressive symptoms of depressive adolescents were evaluated with clinical scale. Serum HMGB1 levels were measured by enzyme-linked immunosorbent assay (ELISA). Correlation analysis, multiple linear regression, and mediation effect analysis were utilized to examine the relationship between serum HMGB1 levels and depressive symptoms severity.Results: Compared with the control group, serum HMGB1 levels (t = -18.48, P <0.001) was increased in depressive adolescents. Correlation analysis showed that serum HMGB1 levels in depressive adolescents were positively correlated with 17-item Hamilton Depression Rating Scale (HAMD-17) scores and Childhood Trauma Questionnaire (CTQ) scores. Multiple linear regression analysis showed that serum HMGB1 levels can independently predict HAMD-17 scores for depressive adolescents. HMGB1 demonstrated high diagnostic accuracy (AUC = 0.984) and significantly mediated depressive symptoms through childhood trauma (indirect effect = 0.0028, 95% CI: 0.0008-0.0058).Conclusion: Serum HMGB1 levels are potential markers of depression, and childhood trauma partially mediates the relationship between HMGB1 and depressive symptoms severity.