Neural effect of childhood maltreatment on neurovascular coupling in adolescent depression

Childhood maltreatment (CM) is a pivotal risk factor for depression, yet its potential contribution to major depressive disorder (MDD) in adolescents requires further investigation. This study aims to scrutinize the specific impact of CM on neurovascular coupling (NVC) in adolescents with MDD. A cohort of 189 adolescents, comprising 54 MDD with CM, 45 MDD without CM, 33 healthy controls (HC) with CM, and 57 HC without CM, underwent multimodal MRI scans. Cerebral blood flow (CBF) was computed to evaluate vascular responses, while functional connectivity strength (FCS) and amplitude of low-frequency fluctuation (ALFF) were measured to assess neuronal activity. NVC was calculated using whole gray matter CBF-neuronal activity correlation coefficients and regional CBF/neuronal activity ratios. MDD×CM interactions on NVC, CBF, and neuronal activity were analyzed, with further exploration of the associations between these abnormal NVC ratios and CM experience. Support vector machine classifiers were employed to differentiate MDD adolescents. Results revealed a significant MDD×CM interactive effect on CBF-FCS coefficients at whole gray matter level. Regionally, these interactions on NVC ratios primarily occurred in the reward systems, including bilateral anterior cingulate/orbitofrontal cortex, thalamus/mesial temporal lobe, and left occipitotemporal lobe, correlating with CM measurements. Notably, the integration of NVC ratio, CBF, and neuronal activity yielded robust classification performance in distinguishing MDD adolescents. These findings reinforce the importance of reward system for MDD adolescents related to CM, proposing a novel neuroimaging biomarker for early recognition of adolescent depression.