Subtypes of adolescent major depressive disorder characterized by divergent information dynamics in sensory-association cortices

Adolescent major depressive disorder (MDD) involves complex and heterogeneous alterations in brain functional organization. A possible explanation is the disruption of individualized brain maturation during adolescence, which typically transitions from lower-order sensory to higher-order association regions. To test this hypothesis, we analyzed resting-state functional MRI data using advanced matrix decomposition techniques to extract organizational gradients, temporal dynamics, and information flow. Clustering sensory–association gradient features in our main sample (NMDD = 302 and NControls = 207; ages 11-17) revealed two subtypes. Subtype 1 showed bottom‑up (sensory‑to‑association) flow, reduced synergy but heightened redundancy in sensory cortices, and a highly modular yet globally inefficient network—patterns consistent with aberrant sensory processing and impaired integration. Subtype 2 instead displayed a top‑down (association‑to‑sensory) flow, reduced synergy in association areas, elevated redundancy in sensory regions, and network efficiency between subtype 1 and healthy controls, suggesting compensatory higher‑order engagement. Subtypes also differed in age-related changes, clinical profiles, and neurobiological processing. These patterns were largely replicated in an independent sample (NMDD = 73 and NControls = 28). Overall, the sensory-association axis distinguishes MDD subtypes, integrating functional heterogeneity, cortical dynamics, developmental trajectories, and genetic influences, offering new insights for pathophysiology and precision psychiatry. In this study, the authors identify two biologically distinct subtypes of adolescent major depressive disorder by analyzing interactions between sensory and higher-order association brain regions, offering new insights for the development of targeted diagnostic and therapeutic approaches.