Altered white matter microstructure in children with attention-deficit/hyperactivity disorder
Open accessAbstract
Objective Identification of biomarkers is a priority for attention-deficit/hyperactivity disorder (ADHD). Studies have documented macrostructural brain alterations in ADHD, but few have examined white matter microstructure, particularly in preadolescent children. Given dramatic white matter maturation across childhood, microstructural differences seen in adolescents and adults with ADHD may reflect compensatory restructuring, rather than early neurophenotypic markers of the disorder.Method Using tract-based spatial statistics, mean fractional anisotropy (FA) maps were created using diffusion tensor imaging. FA, mean diffusivity (MD), and associated axial and radial diffusivities were compared between 16 children with ADHD and 20 healthy children (age 7-9 years).Results Youth with ADHD showed decreased FA in frontoparietal, frontolimbic, cerebellar, corona radiata, and temporo-occipital white matter compared with controls. In addition, ADHD was associated with lower MD in the posterior limb of the internal capsule and frontoparietal white matter and greater MD in frontolimbic white matter. Lower axial diffusion and/or higher radial diffusion were differentially observed for youth with ADHD in earlier versus later maturing areas of group FA/MD difference.Conclusions This study suggests that, even prior to adolescence, ADHD represents a disorder of altered structural connectivity of the brain, characterized by distributed atypical white matter microstructure. In addition, later maturing frontolimbic pathways were abnormal in children with ADHD, likely due to delayed or decreased myelination, a finding not previously demonstrated in the adolescent or adult stages of the disorder. These results suggest that disruptions in white matter microstructure may play a key role in the early pathophysiology of ADHD.
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In children and adolescents, severity of ADHD symptoms is linked to decreased frontal and temporal grey matter, caudate and cerebellar volumes, and decreased FA.
“In children and adolescents, severity of ADHD symptoms was linked to decreased frontal and temporal grey matter, caudate and cerebellar volumes, [7] and decreased FA [15, 21, 26].”
From The brain anatomy of attention-deficit/hyperactivity disorder in young adults—a magnetic resonance imaging study (2017) · cites this paper as [15]
These findings, in part, corroborate previous results of white matter differences associated with symptoms severity.
“These findings, in part, corroborate previous results of white matter differences associated with symptoms severity [15, 16, 21, 26, 55].”
From The brain anatomy of attention-deficit/hyperactivity disorder in young adults—a magnetic resonance imaging study (2017) · cites this paper as [15]
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- Authors
- Nagel, B. J., Bathula, D., Herting, M., Schmitt, C., Kroenke, C. D., Fair, D., & Nigg, J. T.
- Affiliations
- Oregon Health & Science University (US)
- Corresponding author
- Nagel, Bonnie J.
- Venue
- Journal of the American Academy of Child & Adolescent Psychiatry
- Publisher
- Elsevier BV
- Published
- 2011-03
- Volume
- 50
- Issue
- 3
- Pages
- 283-292
- ISSN
- 0890-8567 (ISSN-L)
- PMC
- PMC3150529
- OpenAlex
- W2086827281
- Cited by
- 178
- References
- 60
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 5 · 2023: 10 · 2022: 18 · 2021: 9 · 2020: 12 · 2019: 11 · 2018: 5 · 2017: 11 · 2016: 13 · 2015: 17 · 2014: 23 · 2013: 17 · 2012: 9
- FWCI
- 11.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of the American Academy of Child & Adolescent Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01 MH-59105, R01MH059105, R01MH086654)
- National Institute of Neurological Disorders and Stroke (K08 NS52147, K08NS052147)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- attention deficit hyperactivity disorder, white matter microstructure, fractional anisotropy, mean diffusivity, diffusion tensor imaging, tract-based spatial statistics, myelination, white matter maturation, structural connectivity, children, biomarkers, pathophysiology
- MeSH terms
- Adolescent, Adult, Attention Deficit Disorder with Hyperactivity, Brain, Child, Humans, Nerve Fibers, Myelinated, Neural Pathways, Neuropsychological Tests, Anisotropy, Diffusion Magnetic Resonance Imaging, Leukoencephalopathies
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