Abstract / Summary
Abstract Background White-matter microstructural abnormalities are well documented in Attention-deficit/hyperactivity disorder (ADHD), but whether adult ADHD involves atypical hemispheric lateralization of white-matter organization remains unclear. Using neurite orientation dispersion and density imaging (NODDI), we examined lateralized white-matter microstructural alterations in adults with ADHD. Methods 54 adults with ADHD and 48 healthy controls (HCs) underwent clinical assessment and diffusion-weighted magnetic resonance imaging(MRI). NODDI was applied to quantify white-matter microstructural indices and calculate lateralization indices. Group differences were examined using independent-samples t-tests and multivariate analyses, followed by correlation and regression analyses with clinical symptoms. Results Compared with HCs, adults with ADHD exhibited significantly increased leftward lateralization of free-water fraction (FWF) in the sagittal stratum ( p = 0.002), and increased rightward lateralization of neurite density index (NDI) in the cingulum cingulate gyrus ( p = 0.004). Greater sagittal stratum FWF lateralization was positively associated with ADHD symptom severity, as measured by the Wender Utah Rating Scale and Adult ADHD Self-Report Scale, and remained significant after adjustment for age and sex. In contrast, greater rightward cingulum NDI lateralization was associated with lower PHQ-9 scores in both correlation and regression analyses. Conclusions Adult ADHD is associated with asymmetric white-matter microstructural alterations, particularly increased leftward FWF lateralization in the sagittal stratum. NODDI-derived lateralization indices may provide biologically interpretable measures of ADHD-related white-matter organization, although replication in larger and better-balanced cohorts is needed.