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Arch Gen Psychiatry. 2010 Nov;67(11):1159-67. doi: 10.1001/archgenpsychiatry.2010.139.

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

Author information

  • 1MRC Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London SE5 8AF, United Kingdom. jonna.kuntsi@kcl.ac.uk

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.

PMID:
21041617
[PubMed - indexed for MEDLINE]
PMCID:
PMC3770932
Free PMC Article

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