Distinct patterns of structural brain alterations in adolescent with Major Depressive Disorder relative to controls:...

Major Depressive Disorder (MDD) is a leading cause of disability. While neuroanatomical abnormalities in adults with MDD have been widely investigated, atypical brain development in early adolescents with MDD remains largely unexplored. This study utilized the Adolescent Brain Cognitive Development (ABCD) dataset, including baseline and two-year follow-up data. Participants were divided into MDD (n = 126) and healthy control (HC, n = 7543) groups. To address baseline group imbalances, propensity score matching (PSM) was applied. Linear mixed-effects models were used to examine the group × time interaction effects on cortical volume, adjusting for intracranial volume (ICV), age, and sex. Post-hoc analyses further explored the cortical structural development patterns in both groups. Three distinct patterns of cortical volume changes were observed in MDD participants aged 10-11 years. The first pattern showed decreased cortical volume across widespread regions, including frontal, temporal, and occipital lobes in MDD, while the HC group remained stable. The second pattern indicated increases in the orbitofrontal, precentral, and anterior cingulate cortices in HC, while the MDD group remained stable. The third pattern revealed significant cortical reductions in MDD participants in the inferior and middle temporal regions and posterior cingulate cortex, contrasting with increases in the HC group. These atypical developmental trajectories suggest distinct genetic and and biological processes underlying early adolescent MDD, underscoring the importance of early identification of neurodevelopmental deviations to guide targeted prevention and intervention strategies.