Childhood trauma, inflammatory signatures, and fluoxetine response in adolescent depression: A cross-sectional and...

To elucidate the contribution of inflammatory mediators to the link between childhood trauma (CT) and adolescent major depressive disorder (MDD), and to compare inflammatory profiles and fluoxetine treatment responses between trauma-exposed and non-exposed depressed adolescents.

Ninety-five participants were categorized into healthy control (HC, n = 47), MDD without CT (MDD-nCT, n = 24), and MDD with CT (MDD-CT, n = 24), using the Childhood Trauma Questionnaire (CTQ) and the Children's Depression Rating Scale-Revised (CDRS-R). Levels of 12 plasma cytokines were quantified by flow fluorescent luminescence. MDD patients received 8-week fluoxetine treatment, with cytokine levels and depressive symptoms assessed pre- and post-intervention. Analyses included bootstrap-mediated effect tests, longitudinal comparisons, and high-risk quartile (HRQ) analysis to evaluate multi-cytokine dysregulation.

At baseline, the MDD-CT group exhibited elevated levels of multiple pro-inflammatory cytokines compared to both MDD-nCT and HC. Both MDD groups had increased IL-4 and TNF-α relative to HC. CDRS-R scores positively correlated with pro-inflammatory cytokines and inversely with anti-inflammatory IL-10. Mediation analyses confirmed that specific cytokines and a HRQ score partially mediated the path from childhood trauma to depression severity. After fluoxetine treatment, the MDD-CT group showed significant reductions in multiple cytokines and the HRQ score, while only IL-10 changed in MDD-nCT. Although depressive symptoms improved in both, post-treatment scores remained significantly higher in MDD-CT.

CT defines a distinct inflammatory signature in adolescent MDD, which partially mediates depressive severity. Fluoxetine reduces inflammation more prominently in MDD-CT. Inflammatory markers may serve as potential biomarkers for stratification and targeted treatment in this clinical group.