Alterations in neurovascular coupling are present in adolescent patients with major depressive disorder: An...

Alterations in neuronal activity and cerebral hemodynamics have been reported in adolescent patients with major depressive disorder (MDD), possibly resulting in neurovascular decoupling; however, no neuroimaging evidence has confirmed this disruption. The aim of this study was to investigate the possible presence of neurovascular decoupling and its clinical implications in adolescent MDD patients via resting-state functional magnetic resonance imaging (fMRI) and arterial spin labeling (ASL) imaging.

In this prospective single-center study, we recruited adolescent patients with MDD and age-matched healthy controls (HC) between December 2023 and October 2024 for a comprehensive multimodal MRI investigation. Adolescent MDD patients and HCs underwent resting-state fMRI and ASL imaging to calculate low-frequency fluctuation amplitude (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), degree centrality (DC) and cerebral blood flow (CBF). Across-voxel CBF-ALFF, CBF-fALFF, CBF-DC, and CBF-ReHo correlations were analyzed to evaluate global gray matter neurovascular coupling (NVC), and the regional NVC of the brain region was assessed with the CBF/ALFF, CBF/fALFF, CBF/DC, and CBF/ReHo ratios. Subsequently, Pearson's correlation analyses were conducted to explore the relationship between brain regions exhibiting significant differences in local NVC and clinical Hamilton Depression Scale (HAMD).

This study included 45 adolescent MDD patients (mean age: 16.88 ± 3.02years, male: 32) and 50 sex- and age-matched HCs (mean age: 16.90 ± 2.55years, male: 34). Compared with the HCs, the MDD patients presented lower across-voxel CBF-ALFF, CBF-fALFF, CBF-DC and CBF-ReHo correlations and a lower CBF/ALFF ratio in the right middle temporal gyrus (MTG) and angular gyrus (AG). The brain regions with reduced a CBF/ReHo ratio included the bilateral superior parietal lobule (SPL), the left superior frontal gyrus (SFG), and the left medial superior frontal gyrus (MSFG). The right AG and right MTG, with significant differences in the CBF/ALFF ratio in adolescent MDD patients, were negatively correlated with the clinical HAMD score. The CBF/ReHo ratios in the left MSFG and bilateral SPL were negatively correlated with HAMD scores in adolescent patients with MDD, whereas CBF/ReHo ratios in the left SFG were positively correlated with HAMD scores.

Adolescent patients with MDD presented alterations in NVC mainly in higher-order brain regions in key areas such as emotion regulation, executive function, and cognitive control. These findings provide new insights into the pathophysiology of adolescent MDD and potential imaging biomarkers for assessing cognitive performance in adolescent patients with MDD.