Significance of arterial spin labeling in relation to sertraline treatment response in adolescents with major depressive disorder

BACKGROUND Major depressive disorder (MDD) in adolescents is a serious global mental health issue, often accompanied by significant functional impairment and limited treatment response. A deeper understanding of neurobiological predictors of antidepressant efficacy may therefore enable more targeted and effective interventions. Altered cerebral blood flow (CBF) has been implicated in the pathophysiology of depression. However, the relationship between regional perfusion changes and subsequent treatment outcomes in adolescents remains underexplored. AIM To investigate changes in CBF after eight weeks of sertraline treatment in adolescents with MDD and to determine whether baseline CBF is associated with subsequent clinical response. METHODS Thirty-three adolescents with MDD underwent magnetic resonance imaging scans as well as clinical evaluations at baseline and after eight weeks of sertraline treatment. Specifically, CBF was quantified using arterial spin labeling, while severity of depressive symptoms was assessed with the 17-item Hamilton Depression Rating Scale (HAMD-17). Additionally, voxel-wise analyses compared pre-treatment and post-treatment CBF, with correlation analyses subsequently conducted to examine associations between regional CBF and changes in depressive symptom severity (ΔHAMD scores). RESULTS Sertraline treatment led to a significant reduction in HAMD-17 scores, with 51.5% of participants classified as treatment responders. Voxel-wise analysis further revealed a significant decrease in CBF in the right insular cortex after treatment (t = 4.751, P < 0.001). Notably, higher baseline CBF in the right insula was positively correlated with greater reductions in depressive symptoms (R 2 = 0.183, P = 0.013), whereas post-treatment CBF showed no such association. CONCLUSION Baseline perfusion in the right insular cortex showed an association with subsequent antidepressant response in adolescents with MDD. These exploratory findings do not establish causality or predictive utility; confirmation in randomized, placebo or psychotherapy-controlled trials is required before informing clinical decision making, although they may contribute to understanding neurovascular features related to clinical recovery in youth depression.