Subtypes of adolescent major depressive disorder characterized by divergent information dynamics in sensory-association cortices
Year: 2026
Type: article
Study design: Observational Study
Abstract: 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.
Source: Nature Communications
Institutions: Montreal Neurological Institute and Hospital, Fujian Medical University, Wuhan University of Science and Technology, McGill University, Forschungszentrum Jülich, University Hospital of Geneva, Max Planck Institute for Human Cognitive and Brain Sciences, Beijing Institute of Technology, Yale University, University of British Columbia, University of Electronic Science and Technology of China, Taiyuan University of Technology, Stanford Medicine, Stanford University
Language: English
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: Health Commission of Hubei Province, International Max Planck Research School for Environmental, Cellular and Molecular Microbiology, National Natural Science Foundation of China, China Three Gorges University, Mitacs, China Scholarship Council, Beijing Institute of Technology, Wuhan University, Peking University, Wuhan University of Science and Technology, International Max Planck Research School for Advanced Methods in Process and Systems Engineering, Renmin Hospital of Wuhan University, Graduiertenakademie, Technische Universität Dresden
OpenAlex ID: W7130962723