Shared and specific structural covariance network disruptions in adolescent and adult drug-naïve first-episode major depressive disorder

Major depressive disorder (MDD) exhibits substantial neurodevelopmental heterogeneity in both clinical presentation and neuroimaging features. This study aimed to identify shared and age-specific patterns of structural covariance connectivity and topology in adolescent and adult MDD. In this cross-sectional study, structural MRI data from 1,057 participants (504 first-episode, drug-naïve MDD patients: 174 adolescents and 330 adults; 553 matched controls: 82 adolescents and 471 adults) were analyzed. Individualized structural covariance networks (iSCNs) were constructed based on interregional gray matter probability distributions. Group differences in iSCN connectivity and nodal topological properties were assessed, followed by pooled analyses of diagnosis and age effects and their interaction. Altered iSCN subnetworks underwent functional annotation and clinical correlation analyses. Compared with controls, both adolescent and adult MDD patients showed increased iSCN connectivity primarily among frontal, insular, and subcortical regions, indicating shared patterns of connectivity alteration. Adolescent MDD patients additionally exhibited decreased connectivity among temporoparietal, limbic, and subcortical regions, with concurrent alterations in nodal topological properties. Significant main and interaction effects of MDD diagnosis and age group were found on these network measures, with stage-specific differences in iSCN organization relative to age-matched controls. Reduced insula-cuneus and frontal-accumbens connectivity in adolescent MDD was associated with greater depressive severity. Enhanced subnetwork connectivity was related to emotional face processing and social cognition in adolescent MDD but linked to action observation in adult MDD. Both shared and age-specific alterations in structural covariance networks are evident in adolescent and adult MDD, highlighting age-related differences in network organization consistent with neurodevelopmental models of MDD.