Longitudinal Trajectories of White Matter Development in Attention-Deficit/Hyperactivity Disorder

Few longitudinal studies have investigated whether white matter development reflects differential outcomes for children with and without attention-deficit/hyperactivity disorder (ADHD). To examine whether deviations from typical trajectories of white matter development were associated with the persistence or remission of ADHD symptoms, this study examined microstructural and morphological properties of 71 white matter tracts from 390 high angular diffusion scans acquired prospectively for 62 children with persistent ADHD, 37 children remitted from ADHD, and 85 children without ADHD. Participants (mean age at wave 1 = 10.39 years, scan interval = 18 months) underwent up to 3 magnetic resonance imaging assessments. White matter tracts were reconstructed using TractSeg, a semiautomated method. For each tract, we derived measures of fiber density (microstructure) and fiber bundle cross-section (morphology) using fixel-based analysis. Linear mixed models were used to compare trajectories of fiber development between the persistent ADHD, remitted ADHD, and non-ADHD groups. Compared with the non-ADHD group, the remitted and persistent ADHD groups showed accelerated fiber development in thalamic pathways, striatal pathways, and the superior longitudinal fasciculus. In the remitted ADHD group, accelerated fiber development in corticospinal, frontopontine, striatal-premotor, and thalamo-premotor pathways was associated with greater reductions in ADHD symptom severity. The persistent ADHD group showed ongoing white matter alterations along sensorimotor pathways. These results suggest that variations in white matter development are associated with different clinical trajectories in ADHD. The findings advance our understanding of the neurobiological mechanisms underpinning ADHD symptom progression and provide novel evidence in support of developmental models of ADHD.