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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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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