Smaller total brain volume but not subcortical structure volume related to common genetic risk for ADHD
Open accessAbstract
Background: Mechanistic endophenotypes can inform process models of psychopathology and aid interpretation of genetic risk factors. Smaller total brain and subcortical volumes are associated with attention-deficit hyperactivity disorder (ADHD) and provide clues to its development. This study evaluates whether common genetic risk for ADHD is associated with total brain volume (TBV) and hypothesized subcortical structures in children. Methods: Children 7–15 years old were recruited for a case–control study (N = 312, N = 199 ADHD). Children were assessed with a multi-informant, best-estimate diagnostic procedure and motion-corrected MRI measured brain volumes. Polygenic scores were computed based on discovery data from the Psychiatric Genomics Consortium (N = 19 099 ADHD, N = 34 194 controls) and the ENIGMA + CHARGE consortium (N = 26 577). Results: ADHD was associated with smaller TBV, and altered volumes of caudate, cerebellum, putamen, and thalamus after adjustment for TBV; however, effects were larger and statistically reliable only in boys. TBV was associated with an ADHD polygenic score [β = −0.147 (−0.27 to −0.03)], and mediated a small proportion of the effect of polygenic risk on ADHD diagnosis (average ACME = 0.0087, p = 0.012). This finding was stronger in boys (average ACME = 0.019, p = 0.008). In addition, we confirm genetic variation associated with whole brain volume, via an intracranial volume polygenic score. Conclusion: Common genetic risk for ADHD is not expressed primarily as developmental alterations in subcortical brain volumes, but appears to alter brain development in other ways, as evidenced by TBV differences. This is among the first demonstrations of this effect using molecular genetic data. Potential sex differences in these effects warrant further examination.
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In children, reduced total brain volume is associated with both ADHD and higher polygenic scores for ADHD, and both effects are stronger in males than females.
“In children, reduced total brain volume has been associated with both ADHD and higher polygenic scores for ADHD, with both these effects stronger in males than in females202.”
From Sex and gender in neurodevelopmental conditions (2023) · cites this paper as [202]
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Sex and gender in neurodevelopmental conditions
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- Authors
- Mooney, M. A., Bhatt, P., Hermosillo, R. J. M., Ryabinin, P., Nikolas, M., Faraone, S. V., Fair, D. A., Wilmot, B., & Nigg, J. T.
- Affiliations
- Oregon Health & Science University (US)
- University of Iowa (US)
- SUNY Upstate Medical University (US)
- ORCID
- Venue
- Psychological Medicine
- Publisher
- Cambridge University Press (CUP)
- Published
- 2020-01-24
- Volume
- 51
- Issue
- 8
- Pages
- 1279-1288
- ISSN
- 0033-2917 (ISSN-L)
- 1469-8978
- PMC
- PMC7461955
- OpenAlex
- W3001359011
- Cited by
- 33
- References
- 43
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 5 · 2023: 8 · 2022: 4 · 2021: 4 · 2020: 2
- FWCI
- 3.28
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychological Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5r01mh099064-05)
- National Institute of Mental Health (R01-MH099064, R01MH115357, U01MH109536, R01MH101519, R01MH096773, R01MH086654)
- National Institute on Drug Abuse (U01DA041148)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- attention deficit hyperactivity disorder, total brain volume, subcortical structures, caudate nucleus, cerebellum, putamen, thalamus, polygenic risk, endophenotypes, brain development, sex differences, children, intracranial volume
- MeSH terms
- Adolescent, Attention Deficit Disorder with Hyperactivity, Brain, Child, Female, Humans, Magnetic Resonance Imaging, Male, Risk Factors, Case-Control Studies
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