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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-44178

Kuntsi, J; Wood, A C; Rijsdijk, F; Johnson, K A; Andreou, P; Albrecht, B; Arias-Vásquez, A; Buitelaar, J K; McLoughlin, G; Rommelse, N N J; Sergeant, J A; Sonuga-Barke, E J; Uebel, H; van der Meere, J J; Banaschewski, T; Gill, M; Manor, I; Miranda, A; Mulas, F; Oades, R D; Roeyers, H; Rothenberger, A; Steinhausen, H C; Faraone, S V; Asherson, P (2010). Separation of cognitive impairments in attention-deficit/hyperactivity disorder into 2 familial factors. Archives of General Psychiatry, 67(11):1159-1167.

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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.


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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Child and Adolescent Psychiatry
Dewey Decimal Classification:610 Medicine & health
Date:November 2010
Deposited On:01 Feb 2011 17:33
Last Modified:05 Apr 2016 14:41
Publisher:American Medical Association
Publisher DOI:10.1001/archgenpsychiatry.2010.139
PubMed ID:21041617

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