Nat Biomed Eng. 2026 Aug 31. doi: 10.1038/s41551-026-01779-4. Online ahead of print.
ABSTRACT
Attention deficit hyperactivity disorder (ADHD) lacks validated biomarkers for tracking symptom trajectories or guiding treatment selection in youth. Here we quantify individual deviations from normative age-related trajectories of white-matter structural connectivity across two independent datasets: 6,687 typically developing and 1,114 ADHD scans from a longitudinal developmental cohort, and 355 typically developing and 477 ADHD participants from an independent cohort. Youths with ADHD showed pronounced structural connectivity deviations enriched towards the association end of the sensorimotor-association connectional axis. A subset of higher-order association connections showed ADHD-specific developmental reductions in deviations beyond typical developmental patterns, and these changes mediated age-related declines in ADHD symptoms. Within-individual decreases in deviation over 2 years tracked symptom improvement. Baseline deviations predicted 12-week treatment response to atomoxetine but not methylphenidate, and follow-up imaging revealed treatment-related reductions in deviation. Together, these findings identify structural connectivity deviation as a developmental biomarker with prognostic relevance for ADHD, supporting precision care through symptom monitoring and treatment stratification.
PMID:42675180 | DOI:10.1038/s41551-026-01779-4
