Atypical development in white matter microstructures in ADHD: A longitudinal diffusion imaging study

BACKGROUND: In cross-sectional studies, alterations in white matter microstructure are evident in children with attention-deficit/hyperactivity disorder (ADHD) but not so prominent in adults with ADHD compared to typically-developing controls (TDC). Moreover, the developmental trajectories of white matter microstructures in ADHD are unclear, given the limited longitudinal imaging studies that characterize developmental changes in ADHD vs. TDC. METHODS: This longitudinal study acquired diffusion spectrum imaging (DSI) at two time points. The sample included 55 participants with ADHD and 61 TDC. The enrollment/first DSI age ranged from 7 to 18 years, with a five-year mean follow-up time. We examined time-by-diagnosis interaction on the generalized fractional anisotropy (GFA) of 45 white matter tracts, adjusting for confounding factors and correcting for multiple comparisons. We also tested whether the longitudinal changes of microstructures were associated with ADHD symptoms and attention performance in a computerized continuous performance test. RESULTS: Participants with ADHD showed more rapid development of GFA in the arcuate fasciculus, superior longitudinal fasciculus, frontal aslant tract, cingulum, inferior fronto-occipital fasciculus (IFOF), frontostriatal tract connecting the prefrontal cortex (FS-PFC), thalamic radiation, corticospinal tract, and corpus callosum. Within participants with ADHD, more rapid GFA increases in cingulum and FS-PFC were associated with slower decreases in inattention symptoms. In addition, in all participants, more rapid GFA increases in cingulum and IFOF were associated with greater improvement in attention performance. CONCLUSION: Our findings suggest atypical developmental trajectories of white matter tracts in ADHD, characterized by normalization and possible compensatory neuroplastic processes with age from childhood to early adulthood.