Disrupted Structural Brain Networks and Structural-Functional Decoupling in First-Episode Drug-Naïve Adolescent Major Depressive Disorder.

PURPOSE: Major depressive disorder (MDD) tends to emerge during adolescence, but the neurobiology of adolescent MDD is still poorly understood. This study aimed to explore the topological organization of white matter structural networks and the relationship between structural and functional connectivity in adolescent MDD.

METHODS: Structural and functional magnetic resonance imaging data were acquired from 94 first-episode drug-naïve adolescent MDD patients and 78 healthy adolescents. Whole brain structural and functional brain networks were constructed for each subject. Then, the topological organization of structural brain networks and the coupling strength between structural and functional connectivity were analyzed.

RESULTS: Compared with controls, adolescent MDD patients showed disrupted small-world, rich-club, and modular organizations. Nodal centralities in the medial part of bilateral superior frontal gyrus, bilateral hippocampus, right superior occipital gyrus, right angular gyrus, bilateral precuneus, left caudate nucleus, bilateral putamen, right superior temporal gyrus, and right temporal pole part of superior temporal gyrus were significantly lower in adolescent MDD patients compared with controls. The coupling strength between structural and functional connectivity was significantly lower in adolescent MDD patients compared with controls.

DISCUSSION: Our findings suggest widespread disruption of structural brain networks and structural-functional decoupling in adolescent MDD, potentially leading to reduced network communication capacity.