Personalized Estimates of Brain Cortical Structural Similarity in Major Depressive Disorder: Evidence from a Multi-Site Neuroimaging Dataset

Background: Major depressive disorder (MDD) is increasingly recognized as a highly heterogeneous disorder. Although the person-based similarity index (PBSI) provides a useful framework for characterizing individualized brain structural similarity, existing studies in MDD remain limited by either small samples or a lack of integration across different morphological features. Methods: We used structural MRI data from 1442 patients with MDD and 1277 healthy controls to calculate PBSI scores of cortical morphology measures based on cortical thickness (CT), cortical volume (CV), cortical surface area (SA), and sulcal depth (SD). Group comparisons of whole-brain PBSI and regional contributions to PBSI scores were then performed, and a subgroup analysis in 243 first-episode, drug-naive (FEDN) patients with MDD was further conducted. Results: Patients with MDD showed significant alterations in PBSI. Specifically, PBSI scores were significantly reduced for CT, CV, and SD, whereas no significant group difference was observed for SA in the main analysis. Analyses of regional contributions to PBSI further revealed significant between-group differences across multiple cortical regions. These alterations were mainly distributed in the default mode, ventral attention, and visual networks for CT; in the default mode, ventral attention, sensorimotor, and visual networks for CV; and in the default mode, dorsal attention, frontoparietal, and sensorimotor networks for SD. Similar patterns were also observed in the FEDN MDD subgroup. Conclusions: These findings provide neurobiological evidence for the marked structural heterogeneity of MDD and highlight the potential of PBSI as an individualized neuroimaging marker for more precise diagnosis and personalized intervention.