Separation of cognitive impairments in attention-deficit/hyperactivity disorder into 2 familial factors

Jonna Kuntsi, Alexis C. Wood, Frühling Rijsdijk, Katherine A. Johnson, Penelope Andreou, Björn Albrecht, Alejandro Arias-Vasquez, Jan K. Buitelaar, Gráinne McLoughlin, Nanda N.J. Rommelse, Joseph A. Sergeant, Edmund J. Sonuga-Barke, Henrik Uebel, Jaap J. Van Der Meere, Tobias Banaschewski, Michael Gill, Iris Manor, Ana Miranda, Fernando Mulas, Robert D. OadesHerbert Roeyers, Aribert Rothenberger, Hans Christoph Steinhausen, Stephen V. Faraone, Philip Asherson

Research output: Contribution to journalArticlepeer-review


Context: Attention-deficit/hyperactivity disorder (ADHD) is associated with widespread cognitive impairments, but it is not known whether the apparent multiple impairments share etiological roots or separate etiological pathways exist. A better understanding of the etiological pathways is important for the development of targeted interventions and for identification of suitable intermediate phenotypes for molecular genetic investigations. Objectives: To determine, by using a multivariate familial factor analysis approach, whether 1 or more familial factors underlie the slow and variable reaction times, impaired response inhibition, and choice impulsivity associated with ADHD. Design: An ADHD and control sibling-pair design. Setting: Belgium, Germany, Ireland, Israel, Spain, Switzerland, and the United Kingdom. Participants: A total of 1265 participants, aged 6 to 18 years: 464 probands with ADHD and 456 of their siblings (524 with combined-subtype ADHD), and 345 control participants. Main Outcome Measures: Performance on a 4-choice reaction time task, a go/no-go inhibition task, and a choice-delay task. Results: The final model consisted of 2 familial factors. The larger factor, reflecting 85% of the familial variance of ADHD, captured 98% to 100% of the familial influences on mean reaction time and reaction time variability. The second, smaller factor, reflecting 13% of the familial variance of ADHD, captured 62% to 82% of the familial influences on commission and omission errors on the go/no-go task. Choice impulsivity was excluded in the final model because of poor fit. Conclusions: The findings suggest the existence of 2 familial pathways to cognitive impairments in ADHD and indicate promising cognitive targets for future molecular genetic investigations. The familial distinction between the 2 cognitive impairments is consistent with recent theoretical models -a developmental model and an arousal-attention model - of 2 separable underlying processes in ADHD. Future research that tests the familial model within a developmental framework may inform developmentally sensitive interventions.

Original languageEnglish
Pages (from-to)1159-1167
Number of pages9
JournalArchives of General Psychiatry
Issue number11
StatePublished - Nov 2010
Externally publishedYes


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