White matter microstructure and the variable adult outcome of childhood attention deficit hyperactivity disorder
Open accessAbstract
Changes in cerebral cortical anatomy have been tied to the clinical course of attention deficit hyperactivity disorder (ADHD). We now ask if alterations in white matter tract microstructure are likewise linked with the adult outcome of childhood ADHD. Seventy-five young adults, 32 with ADHD persisting from childhood and 43 with symptom remission were contrasted against 74 never-affected comparison subjects. Using diffusion tensor imaging, we defined fractional anisotropy, a metric related to white matter microstructure, along with measures of diffusion perpendicular (radial) and parallel (axial) to the axon. Analyses were adjusted for head motion, age and sex, and controlled for multiple comparisons and medication history. Tract-based analyses showed that greater adult inattention, but not hyperactivity-impulsivity, was associated with significantly lower fractional anisotropy in the left uncinate (standardized β=-0.37, t=3.28, p=0.002) and inferior fronto-occipital fasciculi (standardized β=-0.37, t=3.29, p=0.002). The ADHD group with symptoms persisting into adulthood had significantly lower fractional anisotropy than the never-affected controls in these tracts, differences associated with medium to large effect sizes. By contrast, the ADHD group that remitted by adulthood did not differ significantly from controls. The anomalies were found in tracts that connect components of neural systems pertinent to ADHD, such as attention control (inferior fronto-occipital fasciculus) and emotion regulation and the processing of reward (the uncinate fasciculus). Change in radial rather than axial diffusivity was the primary driver of this effect, suggesting pathophysiological processes including altered myelination as future targets for pharmacological and behavioral interventions.
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A number of existing cross-sectional and longitudinal studies in patients with cADHD support the role of subcortical structures in the emergence of ADHD by showing that reduction of GM volume in thalamus and striatum, and disruption of WM integrity in the major association and projection tracts, contribute to the etiology of ADHD.
“A number of existing cross-sectional and longitudinal studies in patients with cADHD support the role of subcortical structures in the emergence of ADHD by showing that reduction of GM volume in thalamus and striatum, and disruption of WM integrity in the major association and projection tracts, contribute to the etiology of ADHD (Xia et al., 2012; Cortese et al., 2013; Shaw et al., 2015).”
From A Review of Heterogeneity in Attention Deficit/Hyperactivity Disorder (ADHD) (2019) · cites this paper as Shaw et al., 2015
Decreased connectivity and myelination in these areas may be a stable correlate for ADHD throughout the lifespan.
“Decreased connectivity and myelination in these areas may be a stable correlate for ADHD throughout the lifespan [55].”
From The brain anatomy of attention-deficit/hyperactivity disorder in young adults—a magnetic resonance imaging study (2017) · cites this paper as [55]
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 [55]
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- Authors
- Shaw, P., Sudre, G., Wharton, A., Weingart, D., Sharp, W., & Sarlls, J.
- Affiliations
- National Human Genome Research Institute (US)
- National Institutes of Health (US)
- Corresponding author
- Shaw, Philip
- Venue
- Neuropsychopharmacology
- Published
- 2014-09-22
- Volume
- 40
- Issue
- 3
- Pages
- 746-754
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC4289964
- OpenAlex
- W2083583425
- Semantic Scholar
- d65a444160063937a4b209d6e2a4e3a916ee8dfd
- Cited by
- 77
- References
- 57
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 4 · 2023: 6 · 2022: 11 · 2021: 6 · 2020: 10 · 2019: 7 · 2018: 8 · 2017: 6 · 2016: 7 · 2015: 5
- FWCI
- 4.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health
- National Human Genome Research Institute
- 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, uncinate fasciculus, inferior fronto-occipital fasciculus, radial diffusivity, symptom remission, inattention, hyperactivity/impulsivity, myelination, emotion regulation, reward processing, attentional control
- MeSH terms
- Attention, Attention Deficit Disorder with Hyperactivity, Female, Humans, Impulsive Behavior, Male, Case-Control Studies, Anisotropy, Young Adult, Diffusion Tensor Imaging, White Matter
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