Are endophenotypes based on measures of executive functions useful for molecular genetic studies of ADHD?

Alysa E. Doyle, Stephen V. Faraone, Larry J. Seidman, Erik G. Willcutt, Joel T. Nigg, Irwin D. Waldman, Bruce F. Pennington, Joanne Peart, Joseph Biederman

Research output: Contribution to journalReview articlepeer-review

142 Scopus citations


Background: Behavioral genetic studies provide strong evidence that attention-deficit/hyperactivity disorder (ADHD) has a substantial genetic component. Yet, due to the complexity of the ADHD phenotype, questions remain as to the specific genes that contribute to this condition as well as the pathways from genes to behavior. Endophenotypes, or phenotypes that are more closely linked to the neurobiological substrate of a disorder, offer the potential to address these two issues simultaneously (Freedman, Adler, & Leonard, 1999). Thus far, potential endophenotypes for ADHD have not been systematically studied. Method: The current paper reviews evidence supporting the use of deficits on neurocognitive measures of executive functions for this purpose. Results: Such deficits are a correlate of ADHD and show preliminary evidence of heritability and association with relevant candidate genes. Nonetheless studies that have assessed the familial and genetic overlap of neurocognitive impairments with ADHD have yielded inconsistent results. Conclusions: In order for executive function deficits to be used as an endophenotype for ADHD, we recommend greater attention to the neurocognitive heterogeneity of this disorder and to the precision of measurement of the neuropsychological tests employed. We also discuss empirical strategies that may be necessary to allow such research to progress prior to full resolution of the pathophysiological basis of ADHD.

Original languageEnglish (US)
Pages (from-to)774-803
Number of pages30
JournalJournal of Child Psychology and Psychiatry and Allied Disciplines
Issue number7
StatePublished - Jul 2005
Externally publishedYes


  • ADHD
  • Endophenotype
  • Executive functions
  • Genetics
  • Neuropsychology

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Developmental and Educational Psychology
  • Psychiatry and Mental health


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