Characterizing neuroanatomic heterogeneity in people with and without ADHD based on subcortical brain volumes

The ENIGMA-ADHD Working Group

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Background: Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder. Neuroanatomic heterogeneity limits our understanding of ADHD’s etiology. This study aimed to parse heterogeneity of ADHD and to determine whether patient subgroups could be discerned based on subcortical brain volumes. Methods: Using the large ENIGMA-ADHD Working Group dataset, four subsamples of 993 boys with and without ADHD and to subsamples of 653 adult men, 400 girls, and 447 women were included in analyses. We applied exploratory factor analysis (EFA) to seven subcortical volumes in order to constrain the complexity of the input variables and ensure more stable clustering results. Factor scores derived from the EFA were used to build networks. A community detection (CD) algorithm clustered participants into subgroups based on the networks. Results: Exploratory factor analysis revealed three factors (basal ganglia, limbic system, and thalamus) in boys and men with and without ADHD. Factor structures for girls and women differed from those in males. Given sample size considerations, we concentrated subsequent analyses on males. Male participants could be separated into four communities, of which one was absent in healthy men. Significant case–control differences of subcortical volumes were observed within communities in boys, often with stronger effect sizes compared to the entire sample. As in the entire sample, none were observed in men. Affected men in two of the communities presented comorbidities more frequently than those in other communities. There were no significant differences in ADHD symptom severity, IQ, and medication use between communities in either boys or men. Conclusions: Our results indicate that neuroanatomic heterogeneity in subcortical volumes exists, irrespective of ADHD diagnosis. Effect sizes of case–control differences appear more pronounced at least in some of the subgroups.

Original languageEnglish (US)
Pages (from-to)1140-1149
Number of pages10
JournalJournal of Child Psychology and Psychiatry and Allied Disciplines
Issue number9
Early online dateMar 30 2021
StatePublished - Sep 2021

Bibliographical note

Publisher Copyright:
© 2021 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.


  • ADHD
  • community detection
  • effect sizes
  • neuroanatomic heterogeneity
  • subcortical volume


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