Separation of Cognitive Impairments in Attention-Deficit/Hyperactivity Disorder Into 2 Familial Factors

Jonna Kuntsi*, Alexis C. Wood, Fruehling Rijsdijk, Katherine A. Johnson, Penelope Andreou, Bjoern Albrecht, Alejandro Arias-Vasquez, Jan K. Buitelaar, Grainne 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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

120 Citations (Scopus)

Abstract

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
Volume67
Issue number11
DOIs
Publication statusPublished - Nov-2010

Keywords

  • DEFICIT HYPERACTIVITY DISORDER
  • GENOME-WIDE ASSOCIATION
  • INTRA-SUBJECT VARIABILITY
  • REACTION-TIME PERFORMANCE
  • RESPONSE VARIABILITY
  • SUSTAINED ATTENTION
  • DELAY AVERSION
  • GENETIC INFLUENCES
  • MOLECULAR-GENETICS
  • INHIBITORY CONTROL

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