Unraveling the altered trajectories of cerebellar gray matter volume in attention-deficit/hyperactivity disorder.

Increasing evidence implicates atypical cerebellar development in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). However, the trajectories of cerebellar subregions from childhood into adulthood-and the impact of ADHD on those trajectories-remain unclear. We analyzed the publicly available ADHD-200 dataset, comprising 871 participants aged 7.09-20.90 years (325 with ADHD, 546 typically developing [TD] controls). High-resolution T1-weighted images were processed with the automated CERES segmentation pipeline to obtain absolute gray matter volumes for the whole cerebellum and 12 lobular subdivisions (lobules I-VI, VIIB, VIIIA, VIIIB, IX-X, and crus I-II). Relative volume is also employed in this study, which refers to the relative proportion of absolute volume to intracranial volume. Age-related change was modeled with linear regression models that included diagnosis-by-age interactions. For absolute volume, a significant age-by-diagnosis interaction was observed in the right lobule I-II and bilateral lobule X. Follow-up analyses revealed that, compared with TD individuals, those with ADHD exhibited a steeper age-related increase in gray matter volume in these regions, indicating smaller volumes at younger ages and a more pronounced age-associated rise across the observed age range. For relative volume, significant age-by-diagnosis interaction effects were found in the bilateral lobule IV and bilateral crus II. Follow-up analyses indicated that both ADHD and TD individuals showed age-related decreases in gray matter volume; however, this decline was more pronounced in the ADHD group. Taken together, the divergent age-related patterns of absolute and relative gray matter volume suggest that overall intracranial volume expansion may lag behind cerebellar growth in ADHD, such that the relative cerebellar differences are proportionally less marked than the global brain differences. These findings unravel normative and ADHD developmental trajectories of cerebellar gray matter volume from childhood through adulthood and provide a neuroanatomical framework for optimizing the cerebellum-focused prevention and intervention strategies in ADHD.