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
Abstract
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 Conclusions When conceptualizing neurodevelopmental disorders as white matter tract deviations from normative patterns, ASD and ADHD are more alike than different. The modest white matter tract alterations in siblings suggest potential endophenotypes in these at-risk populations. This study further delineates brain-driven dimensions of psychopathology/cognition, which may help clarify within-diagnosis heterogeneity and high between-diagnosis co-occurrence.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Previous large scale studies and meta-analyses of neuroimaging, neurophysiological and neuropsychological impairments have highlighted areas of overlap, particularly between ADHD and ASD.
“Similarly, previous large scale studies and meta-analyses of neuroimaging, neurophysiological and neuropsychological impairments have highlighted areas of overlap, particularly between ADHD and ASD 53-56 .”
From Candidate diagnostic biomarkers for neurodevelopmental disorders in children and adolescents: a systematic review (2023) · cites this paper as [56]
No citation lists for this paper
No citation lists for this paper yet — checked again daily.
References 60 · Cited by 79
- Authors
- Tung, Y.-H., Lin, H.-Y., Chen, C.-L., Shang, C.-Y., Yang, L.-Y., Hsu, Y.-C., Tseng, W.-Y. I., & Gau, S. S.-F.
- Affiliations
- Centre for Addiction and Mental Health (CA)
- School of Medicine, National Taiwan University College of Medicine, and Department of Medical Education, National Taiwan University Hospital, Taipei (Tung); Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei (Tung, Lin, Shang, Gau); Azrieli Adult Neurodevelopmental Centre and Adult Neurodevelopmental and Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto (Lin); Department of Psychiatry, University of Toronto, Toronto (Lin); Institute...
- ORCID
- Venue
- American Journal of Psychiatry
- Published
- 2021-08-01
- Volume
- 178
- Issue
- 8
- Pages
- 730-743
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- OpenAlex
- W3136016100
- Cited by
- 79
- References
- 60
- Citations by year
- 2026: 15 · 2025: 15 · 2024: 15 · 2023: 14 · 2022: 15 · 2021: 5
- FWCI
- 6.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Keywords
- autism spectrum disorder, attention deficit hyperactivity disorder, unaffected siblings, endophenotypes, corpus callosum, psychopathology dimensions, cognitive dimension, diffusion MRI, neurodevelopmental disorders
- MeSH terms
- Adolescent, Adult, Attention Deficit Disorder with Hyperactivity, Autistic Disorder, Brain, Child, Child, Preschool, Cognition, Female, Humans, Male, Neural Pathways, Psychopathology, Sex Factors, Case-Control Studies, Siblings, Young Adult, Neuroimaging, White Matter
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
