Multimodal gray matter morphological alterations in cognitive subtypes of adolescent major depressive disorder

Abstract Objective This study compares brain structure between two cognitive subtypes of adolescent Major depressive disorder (MDD). It uses voxel-based morphometry (VBM) and surface-based morphometry (SBM)to examine group differences. It also tests how these structural changes relate to cognitive performance and clinical indicators. The goal is to understand why adolescents with MDD show different cognitive patterns. Methods The study recruited 85 adolescents with MDD and 30 healthy controls. All participants underwent magnetic resonance imaging (MRI) scans and neuropsychological testing. K-means clustering divided the MDD group into cognitive impairment (MDD-I) and cognitive preservation (MDD-II). VBM and SBM analyses assessed structural differences across groups. Correlation analyses tested associations between brain features and clinical indicators. Results MDD-I showed widespread gray matter reduction and cortical thinning, particularly in the prefrontal, insular, temporal, and postcentral regions. The MDD-II showed milder and more localized structural changes. The cortical thickness of the bilateral postcentral gyrus in MDD-I was negatively correlated with inhibitory control function; the gray matter volume of the left middle frontal gyrus in MDD-II was positively correlated with short-term memory function. Conclusion Our results show clear structural differences between cognitive subtypes of adolescent MDD. These data support a neuroanatomical basis for cognitive heterogeneity. Multimodal imaging adds complementary evidence and may provide a potential direction for future stratified diagnosis and treatment.