Distinct developmental changes in regional gray matter volume and covariance in individuals with attention-deficit hyperactivity disorder: A longitudinal voxel-based morphometry study

Background: Very few studies have investigated longitudinal clinical cohorts of attention-deficit/hyperactivity disorder (ADHD). Moreover, how baseline brain changes could affect the development of ADHD symptoms later in life remains elusive. Therefore, we aimed to fill this gap by exploring brain and clinical changes in youth with ADHD using a longitudinal design. Methods: This prospective study consisted of 74 children and adolescents with ADHD and 50 age-, sex-, intelligence-matched typically developing controls (TDC), evaluated at baseline (aged 7-19 years) and reevaluated 5.3 years later (a mean follow-up latency). We applied voxel-based morphometry to characterize brain structures, followed by both mass-univariate and multivariate structural covariance statistics to identify brain regions with significant diagnosis-by-time interactions from late childhood/adolescence to early adulthood. We used the cross-lagged panel model to investigate the longitudinal association between structural brain metrics and core ADHD symptoms. Results: The mass-univariate statistic revealed significant diagnosis-by-time interactions in the right striatum and the sixth lobule of the cerebellum. This was expressed by increased striatal and decreased cerebellar volume in ADHD, while TDC showed inverse volume changes over time. The multivariate method showed significant diagnosis-by-time interactions in a structural covariance network consisting of the regions involved in the functional sensory-motor and default-mode networks. Higher baseline right striatal and cerebellar volumes were associated with elevated ADHD symptoms at follow-up. Conclusions: Our findings suggest a temporal association between the divergent development of striatal and cerebellar regions and dynamical ADHD phenotypic expression through young adulthood. These results highlight a potential brain marker of future outcomes.