Sex-Based Dissociation of White Matter Microstructure in Children With Attention-Deficit/Hyperactivity Disorder
Open accessAbstract
Objective Sexual dimorphism is evident in attention-deficit/hyperactivity disorder (ADHD), including subtype prevalence, adverse outcomes, and neural phenotype. Neurobiological studies of ADHD suggest that boys show more abnormalities in motor and premotor structure and function, whereas girls differ from typically developing (TD) peers in prefrontal circuitry. We applied diffusion tensor imaging (DTI) to identify ADHD-related sex-specific differences in motor/premotor and prefrontal white matter (WM) microstructure in children.Method DTI estimated differences in WM microstructure among 120 children 8 to 12 years of age, 60 with ADHD (30 boys and 30 girls) and 60 controls (30 boys and 30 girls), matched on age, IQ, and handedness. Effects of diagnosis and sex on fractional anisotropy (FA) were assessed in motor/premotor and prefrontal regions. Group differences in FA and associations with response control (e.g., reaction time variability [CVRT] and commission error rate) were examined separately within sex.Results Sex-by-diagnosis interactions were observed for FA in primary motor (M1) and medial orbitofrontal (MOFC) cortex. Post hoc tests revealed that boys with ADHD showed bilateral reductions in FA within M1, compared with TD peers; in contrast, girls with ADHD showed higher FA bilaterally within MOFC. Decreased M1 FA was associated with higher CVRT in boys and higher commission error rates in girls. For MOFC, lower FA was associated with greater CVRT and commission error rates across all participants with ADHD.Conclusion ADHD affects the white matter of boys and girls differently; boys appear to be more affected in regions responsible for control of basic actions, whereas girls show more abnormalities in regions responsible for higher-level, top-down control.
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A study in school-aged children found sex/gender-by-diagnosis interaction effects on white matter microstructure measures, which also correlated with inhibitory control performance.
“A study in school-aged children identified sex/gender-by-diagnosis interaction effects on measures of white matter microstructure, which also correlated with inhibitory control performance205.”
From Sex and gender in neurodevelopmental conditions (2023) · cites this paper as [205]
Compared with neurotypical participants, males with ADHD had fractional anisotropy alterations in primary motor regions, whereas females with ADHD had alterations in medial orbitofrontal regions.
“More specifically, compared with neurotypical participants, males diagnosed with ADHD had alterations in fractional anisotropy in primary motor regions, whereas ADHD females had alterations in medial orbitofrontal regions.”
From Sex and gender in neurodevelopmental conditions (2023) · cites this paper as [205]
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- Authors
- Jacobson, L. A., Peterson, D. J., Rosch, K. S., Crocetti, D., Mori, S., & Mostofsky, S. H.
- Affiliations
- Kennedy Krieger Institute (US)
- Corresponding author
- Jacobson, Lisa A.
- ORCID
- Venue
- Journal of the American Academy of Child & Adolescent Psychiatry
- Publisher
- Elsevier BV
- Published
- 2015-11
- Volume
- 54
- Issue
- 11
- Pages
- 938-946
- ISSN
- 0890-8567 (ISSN-L)
- PMC
- PMC4624101
- OpenAlex
- W1921706227
- Cited by
- 44
- References
- 49
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 9 · 2022: 6 · 2021: 6 · 2020: 1 · 2019: 3 · 2018: 3 · 2017: 6 · 2016: 1
- FWCI
- 2.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of the American Academy of Child & Adolescent Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Johns Hopkins University (UL1 TR 000424-06)
- National Institutes of Health (UL1TR000424, EB015909, MH101322)
- National Institute of Mental Health (R01MH085328, R01MH078160, K23MH101322)
- National Institute of Neurological Disorders and Stroke (R01NS084957)
- National Institute of Biomedical Imaging and Bioengineering (P41EB015909)
- National Center for Research Resources
- National Center for Advancing Translational Sciences
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD079123)
- 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, sex differences, white matter microstructure, fractional anisotropy, primary motor cortex, medial orbitofrontal cortex, response control, reaction time variability, commission errors, children, diffusion tensor imaging
- MeSH terms
- Behavior Rating Scale, Attention Deficit Disorder with Hyperactivity, Child, Female, Frontal Lobe, Humans, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Psychiatric Status Rating Scales, Reaction Time, Sex Characteristics, Case-Control Studies, Anisotropy, Diagnostic and Statistical Manual of Mental Disorders, Diffusion Tensor Imaging, White Matter
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