Journal article
Smaller total brain volume but not subcortical structure volume related to common genetic risk for ADHD
Psychological medicine, Vol.51(8), pp.1-1288
01/24/2020
DOI: 10.1017/S0033291719004148
PMCID: PMC7461955
PMID: 31973781
Abstract
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.
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).
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.
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.
Details
- Title: Subtitle
- Smaller total brain volume but not subcortical structure volume related to common genetic risk for ADHD
- Creators
- Michael A Mooney - OHSU Knight Cancer Institute, Portland, Oregon, USAPriya Bhatt - Department of Psychiatry, Oregon Health & Science University, Portland, Oregon, USARobert J M Hermosillo - Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USAPeter Ryabinin - Oregon Clinical and Translational Research Institute, Portland, Oregon, USAMolly Nikolas - Department of Psychological and Brain Sciences, The University of Iowa, Iowa City, Iowa, USAStephen V Faraone - Departments of Psychiatry and Neuroscience & Physiology, State University of New York Upstate Medical University, Syracuse, New York, USADamien A Fair - Advanced Imaging Research Center, OHSU, Portland, Oregon, USABeth Wilmot - Oregon Clinical and Translational Research Institute, Portland, Oregon, USAJoel T Nigg - Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USA
- Resource Type
- Journal article
- Publication Details
- Psychological medicine, Vol.51(8), pp.1-1288
- DOI
- 10.1017/S0033291719004148
- PMID
- 31973781
- PMCID
- PMC7461955
- NLM abbreviation
- Psychol Med
- ISSN
- 0033-2917
- eISSN
- 1469-8978
- Language
- English
- Date published
- 01/24/2020
- Academic Unit
- Psychological and Brain Sciences; Injury Prevention Research Center
- Record Identifier
- 9984213399802771
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