Brain Myelin in Children With Attention-Deficit/Hyperactivity Disorder: A Longitudinal T1-Weighted/T2-Weighted Ratio...

Research has demonstrated a broad network of dysfunction across the brain in attention-deficit/hyperactivity disorder (ADHD), suggesting the potential role of white matter (WM) organization. In this study, we sought to estimate the developmental trajectories of brain WM myelination in children with ADHD.

Neuroimaging and clinical data were collected as part of a longitudinal community-based pediatric cohort (N_scans = 400; 195 with ADHD; age range = 9-14 years). Brain WM myelin was examined for 71 WM tracts across 3 time points using the T1-weighted (T1w)/T2-weighted (T2w) ratio. Tracts were defined via a deep learning-based automated tractography method, performed on participant diffusion-weighted images. Linear and nonlinear regression analyses were conducted to examine group differences in T1w/T2w ratio values. In addition to this, voxelwise analysis was undertaken at each time point.

Brainwide, children with ADHD were found to exhibit the same developmental profile as children without ADHD for WM myelin. No group effects were seen at a cross-sectional or longitudinal level. Consistent with previous work, modeling suggests nonlinear developmental increases with age across most tracts. This nonlinear relationship was characterized by a positive parabolic or U-shaped developmental trajectory.

These findings indicate that there may not be distinct differences in the development of brain WM myelination between children with and without ADHD. However, this suggests that previously reported differences in ADHD brain WM development may be attributable to properties other than myelin, such as fiber architecture and axon diameter. This further informs the understanding of brain development and highlights the need for more multimodal longitudinal work.