White Matter Alterations at 33-Year Follow-Up in Adults with Childhood Attention-Deficit/Hyperactivity Disorder

Background: Attention-deficit/hyperactivity disorder (ADHD) is increasingly conceived as reflecting altered functional and structural brain connectivity. The latter can be addressed with diffusion tensor imaging (DTI). We examined fractional anisotropy (FA), a DTI index related to white matter structural properties, in adult male subjects diagnosed with ADHD in childhood (probands) and matched control subjects without childhood ADHD. Additionally, we contrasted FA among probands with and without current ADHD in adulthood and control subjects. Methods: Participants were from an original cohort of 207 boys and 178 male control subjects. At 33-year follow-up, analyzable DTI scans were obtained in 51 probands (41.3 +/- 2.8 yrs) and 66 control subjects (41.2 +/- 3.1 yrs). Voxel-based FA was computed with tract-based spatial statistics, controlling for multiple comparisons. Results: Probands with childhood ADHD exhibited significantly lower FA than control subjects without childhood ADHD in the right superior and posterior corona radiata, right superior longitudinal fasciculus, and in a left cluster including the posterior thalamic radiation, the retrolenticular part of the internal capsule, and the sagittal stratum (p < .05, corrected). Fractional anisotropy was significantly decreased relative to control subjects in several tracts in both probands with current and remitted ADHD, who did not differ significantly from each other. Fractional anisotropy was not significantly increased in probands in any region. Conclusions: Decreased FA in adults with childhood ADHD regardless of current ADHD might be an enduring trait of ADHD. White matter tracts with decreased FA connect regions involved in high-level as well as sensorimotor functions, suggesting that both types of processes are involved in the pathophysiology of ADHD.