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Separation of Cognitive Impairments in Attention-Deficit/Hyperactivity Disorder Into 2 Familial Factors
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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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“Neurocognitive, neuroimaging and genetic theories of ADHD have shifted from single-cause or singlepathway models to models that delineate causes that lead to ADHD through several molecular, neural and neurocognitive pathways 33,98-102 .”
From Attention-deficit/hyperactivity disorder (2015) · cites this paper as [102]
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“These approaches have received clear support from aetiological studies indicating that most cases of ADHD arise from a 'pool' of genetic and environmental risk factors.”
From Attention-deficit/hyperactivity disorder (2015) · cites this paper as [102]
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“The last domain is output speed, also of interest in ADHD.16”
From Working Memory and Vigilance as Multivariate Endophenotypes Related to Common Genetic Risk for Attention-Deficit/Hyperactivity Disorder (2018) · cites this paper as [16]
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Metadata
- Authors
- Kuntsi, J., Wood, A. C., Johnson, K. A., Andreou, P., Arias-Vasquez, A., Buitelaar, J. K., 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.
- Affiliations
- University of London (GB)
- Queen's University Belfast (GB)
- Radboud University Nijmegen (NL)
- Vrije Universiteit Amsterdam (NL)
- Ghent University (BE)
- University of Göttingen (DE)
- Heidelberg University (DE)
- Trinity College Dublin (IE)
- Herzog Hospital (IL)
- Universitat de València (ES)
- Hospital Universitari i Politècnic La Fe (ES)
- University of Duisburg-Essen (DE)
- University of Basel (CH)
- State University of New York (US)
- ORCID
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2010-11-01
- Volume
- 67
- Issue
- 11
- Pages
- 1159
- ISSN
- 0003-990X (ISSN-L)
- PMC
- PMC3770932
- OpenAlex
- W1965816907
- Cited by
- 162
- References
- 71
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 8 · 2022: 3 · 2021: 8 · 2020: 11 · 2019: 9 · 2018: 13 · 2017: 8 · 2016: 18 · 2015: 13 · 2014: 15 · 2013: 16 · 2012: 15
- FWCI
- 11.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- DuEPublico (University of Duisburg-Essen) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (R01 MH 62873, R01MH081803, R01MH062873)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Social Sciences › Psychology › Neuropsychology and Physiological Psychology › Developmental and Educational Neuropsychology
- Keywords
- attention deficit hyperactivity disorder, cognitive impairment, family factors, reaction time variability, response inhibition, go/no-go task, impulsivity, choice impulsivity, endophenotypes, developmental model
- MeSH terms
- Adolescent, Attention Deficit Disorder with Hyperactivity, Child, Choice Behavior, Cognition Disorders, Factor Analysis, Statistical, Family, Female, Humans, Impulsive Behavior, Male, Neuropsychological Tests, Pedigree, Phenotype, Reaction Time, Comorbidity, Siblings
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