Brain imaging of the cortex in ADHD: A coordinated analysis of large-scale clinical and population-based samples

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Neuroimaging studies show structural alterations of various brain regions in children and adults with ADHD, although non-replications are frequent. Our aim is to identify cortical characteristics related to ADHD using large-scale studies. Methods: Cortical thickness and surface area (based on the Desikan–Killiany atlas) were compared between cases (n=2246) and controls (n=1934) for children, adolescents, and adults separately in ENIGMA-ADHD, a consortium of 36 centers. To assess familial effects on cortical measures, cases, unaffected siblings, and controls in the NeuroIMAGE study (n=506) were compared. Associations of the attention scale from the Child Behavior Checklist with cortical measures were determined in a pediatric population sample (Generation-R, n=2707). Results: In ENIGMA-ADHD, lower surface area values were found in children with ADHD, mainly in frontal, cingulate, and temporal regions; the largest effect was for total surface area (Cohen’s d=-0.21; pFDR=<0.001). Fusiform gyrus and temporal pole cortical thickness was also lower in children with ADHD. Neither surface area nor thickness differences were found in the adolescents/adult groups. Familial effects were seen for surface area in several regions. In an overlapping set of regions, surface area, but not thickness, was associated with attention problems in Generation-R. Conclusion: Subtle differences in cortical surface area are widespread in children, but not in adolescents and adults with ADHD, confirming involvement of frontal cortex and highlighting regions deserving further attention. Importantly, the alterations behave like endophenotypes in families and are linked to ADHD symptoms in the population, extending evidence that ADHD behaves as a continuous trait in the population. Future longitudinal studies should clarify individual lifespan trajectories that lead to non-significant findings in adolescent/adult groups despite presence of an ADHD diagnosis.
Original languageEnglish
Pages (from-to)531-542
Number of pages12
JournalThe American Journal of Psychiatry
Issue number7
Early online date19 Apr 2019
Publication statusPublished - 1 Jul 2019


  • Attention Deficit Hyperactivity Disorder
  • Cortical Surface Area
  • Cortical Thickness
  • Imaging
  • Meta-Analysis
  • Neuroanatomy


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