Whole Brain White Matter Tract Deviation and Idiosyncrasy From Normative Development in Autism and ADHD and Unaffected Siblings Link With Dimensions of Psychopathology and Cognition

Objective: The heterogeneity of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) preclude definitive identification of neurobiomarkers and biological risks. High clinical overlap suggests multifaceted circuit-level alterations across diagnoses, which remains elusive. This study investigated whether individuals with ADHD or ASD and their unaffected siblings constitute a spectrum of neurodevelopmental conditions in terms of white matter etiology. Methods: Sex-specific white matter tract normative development was modeled from diffusion MRI of 626 typically developing control subjects (ages 5–40 years; 376 of them male). Individualized metrics estimating white matter tract deviation from the age norm were derived for 279 probands with ADHD, 175 probands with ASD, and their unaffected siblings (ADHD, N=121; ASD, N=72). Results: ASD and ADHD shared diffuse white matter tract deviations in the commissure and association tracts (rho=0.54; p