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The Separation of ADHD Inattention and Hyperactivity-Impulsivity Symptoms: Pathways from Genetic Effects to Cognitive Impairments and Symptoms
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Both shared and unique genetic risk factors underlie the two symptom domains of attention deficit hyperactivity disorder (ADHD): inattention and hyperactivity-impulsivity. The developmental course and relationship to co-occurring disorders differs across the two symptom domains, highlighting the importance of their partially distinct etiologies. Familial cognitive impairment factors have been identified in ADHD, but whether they show specificity in relation to the two ADHD symptom domains remains poorly understood. We aimed to investigate whether different cognitive impairments are genetically linked to the ADHD symptom domains of inattention versus hyperactivity-impulsivity. We conducted multivariate genetic model fitting analyses on ADHD symptom scores and cognitive data, from go/no-go and fast tasks, collected on a population twin sample of 1,312 children aged 7-10. Reaction time variability (RTV) showed substantial genetic overlap with inattention, as observed in an additive genetic correlation of 0.64, compared to an additive genetic correlation of 0.31 with hyperactivity-impulsivity. Commission errors (CE) showed low additive genetic correlations with both hyperactivity-impulsivity and inattention (genetic correlations of 0.17 and 0.11, respectively). The additive genetic correlation between RTV and CE was also low and non-significant at -0.10, consistent with the etiological separation between the two indices of cognitive impairments. Overall, two key cognitive impairments phenotypically associated with ADHD symptoms, captured by RTV and CE, showed different genetic relationships to the two ADHD symptom domains. The findings extend a previous model of two familial cognitive impairment factors in combined subtype ADHD by separating pathways underlying inattention and hyperactivity-impulsivity symptoms.
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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 [33]
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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 [33]
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“Family and twin studies have also demonstrated that genetic influences are shared between ADHD and a wide range of other neurodevelopmental and psycho pathological traits and disorders, including conduct disorder and problems 32 , cognitive performance 33 , autism s pectrum disorders 34 and mood disorders 35,36 .”
From Attention-deficit/hyperactivity disorder (2015) · cites this paper as [33]
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ADHD Working Group of the Psychiatric Genomics Consortium (PGC), Demontis, D., Early Lifecourse & Genetic Epidemiology (EAGLE) Consortium, 23andMe Research Team, Walters, R. K., Martin, J., Mattheisen, M., Als, T. D., Agerbo, E., Baldursson, G., et al. (2019) · Nature Genetics · doi:10.1038/s41588-018-0269-7 · Cited by 2,203
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“We examined inattention and hyperactivity/impulsivity separately based on evidence that these symptom clusters differentially impact other ADHDrelated impairments (Kuntsi et al., 2014), but we did not have specific hypotheses for these symptom clusters due to mixed findings in extant literature.”
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“…indicating that reaction time variability was genetically correlated with both inattention and hyperactivity ADHD symptoms in a twin sample from the general population whereas commission errors presented lower and non-significant genetic correlations with these symptoms [Kuntsi et al., 2014].”
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Gould, K. L., Coventry, W. L., Olson, R. K., & Byrne, B. (2017) · Research on Child and Adolescent Psychopathology · doi:10.1007/s10802-017-0268-7 · Cited by 88
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“Children with ADHD present symptoms of inattention, hyperactivity, and/or impulsivity (Kuntsi et al., 2014).”
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“The contemporary literature regards hyperactivity and attention deficit as two related but separate constructs (Kuntsi et al., 2014; Willcutt et al., 2012).”
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“Selection of Cognitive Variables for Analyses To limit the total number of variables and to enable a comparison to our previous analyses (Kuntsi et al. 2010, 2014) summed scores were obtained across two tasks or conditions as follows: unstandardized RTV across fast task baseline condition and go/…”
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“In twin analyses the genetic association of RTV was observed particularly strongly with inattention symptoms (28).”
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“Thirdly, inattention and hyperactivity-impulsivity are considered separately in view of their partly distinct genetic etiologies, cognitive substrates, comorbidities and dissociable developmental trajectories (Kuntsi et al., 2014; Larsson et al., 2011; Weiler et al., 2000; Willcutt et al., 2007; Wood et al., 2009).”
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“statistical power to detect unique genetic contributions after controlling for all covariates (Kuntsi et al., 2014).”
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“Another overlapping set of associations was observed for rs7984966 in HTR2A with RTV, RD and inattention, implicating it as a potential candidate marker, in line with our previous quantitative genetic finding that the association of RTV and RD with ADHD largely reflects genetic influences shared with inattention that…”
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“ADHD is a multifactorial disorder, and genetic factors might be associated with the risk of ADHD [17, 18].”
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“Our previous research indicates very high phenotypic and genetic/familial correlations (.8–.9) between RTV and MRT, suggesting they capture largely the same process on both the Fast task and the GNG task (Kuntsi et al., 2010, 2014).”
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“The findings from the sibling and twin studies (Kuntsi et al., 2010, 2014) suggested a potential separation, at the genetic level, between attention regulation and response inhibition processes in their association with ADHD.”
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“A prior study by Kuntsi and colleagues (Kuntsi et al., 2014) measured shared and independent genetic influences on ADHD symptom domains, reaction time, VRT, and commission errors among school-age twins.”
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The aetiological association between the dynamics of cortisol productivity and ADHD
Pinto, R., Rijsdijk, F. V., Ouellet‐Morin, I., Asherson, P. J., McLoughlin, G., & Kuntsi, J. (2016) · Journal of Neural Transmission · doi:10.1007/s00702-016-1534-5 · Cited by 10
“Moreover, a series of analyses have highlighted the comparability of our quantitative genetic findings across both diagnostic and dimensional approaches to the ADHD phenotype (Cheung et al. 2012, 2014; Kuntsi et al. 2010, 2014; Paloyelis et al. 2010; Wood et al. 2010a, 2011).”
BackgroundSelf-citationАлександрович, В. И., Ouellet‐Morin, I., Petitclerc, A., Morneau‐Vaillancourt, G., Brendgen, M. R., Dionne, G., Vitaro, F., & Boivin, M. (2024) · JCPP Advances · doi:10.1002/jcv2.12222 · Cited by 8
“…substantial genetic specificity that links inattention to cognitive deficit, learning disability and educational outcomes (DuPaul & Volpe, 2009; Greven, Harlaar, et al., 2011; Kuntsi et al., 2014), and hyperactivity to oppositional and substance use problems (Quinn et al., 2016; Wood et al., 2009).”
BackgroundAttention Deficit Hyperactivity Disorder: Insight from Quantitative Genetic Research
Wood, A. C., Rommel, A., & Kuntsi, J. (2014) · Springer eBooks · doi:10.1007/978-1-4614-9509-3_1 · Cited by 8
Self-citationSanchez, M. S., Bussu, G., Portugal, A. M., Ronald, A., & Falck‐Ytter, T. (2024) · Child Development · doi:10.1111/cdev.14185 · Cited by 7
Current Perspectives on Attention-deficit Hyperactivity Disorder
Shafiullah, S., & Dhaneshwar, S. S. (2023) · Current Molecular Medicine · doi:10.2174/1566524023666230522145950 · Cited by 9
Catelan, R. F., Zsila, Á., Pietkiewicz, I. J., & Nardi, A. E. (2023) · Psychiatria i Psychologia Kliniczna · doi:10.15557/pipk.2023.0018 · Cited by 7
The Age of Onset of Attention-Deficit Hyperactivity Disorder
Coghill, D., Asherson, P. J., Faraone, S. V., & Rohde, L. A. (2018) · Springer eBooks · doi:10.1007/978-3-319-72619-9_12 · Cited by 8
Self-citationDevelopment of graphomotor fluency in adults with ADHD: Evidence of attenuated procedural learning.
Duda, T. A., Casey, J., & McNevin, N. (2015) · Human Movement Science · doi:10.1016/j.humov.2015.08.006 · Cited by 7
“…in nature, with research implicating interactions between genetic and environmental factors and their neurological corollaries as primary causal agents (Cortese, 2012; Koziol, Budding, & Chidekel, 2013; Kuntsi et al., 2014; McLoughlin, Palmer, Rijsdijk, & Makeig, 2014; Merwood et al., 2014).”
BackgroundKoltermann, G., Becker, N., Paiva, G. M., Gomides, M. R. D. A., Haase, V. G., & de Salles, J. F. (2020) · Developmental Neuropsychology · doi:10.1080/87565641.2020.1828424 · Cited by 8
Tansey, R., Graff, K., Rohr, C. S., Dimond, D., Ip, A., Dewey, D., & Bray, S. (2022) · Cerebral Cortex Communications · doi:10.1093/texcom/tgac011 · Cited by 6
“Studies suggest that in the general population, inattention and hyperactivity have differential associations with cognitive measures (Kuntsi et al. 2014), symptom trajectories (Larsson et al.”
BackgroundSchermer, J. A., & Vernon, P. A. (2015) · Journal of Intelligence · doi:10.3390/jintelligence3040160 · Cited by 5
“Typically studies examining the relationship between reaction time and intelligence are conducted with adult participants (see [1]), although some have examined adolescents [2,3] and others have looked at young twins with clinical issues such as attention deficit hyperactivity disorder [4].”
Anning, K. L., Langley, K., Hobson, C. W., de Sonneville, L. M. J., & van Goozen, S. H. M. (2023) · Child Neuropsychology · doi:10.1080/09297049.2023.2190964 · Cited by 6
“Anxiety may inhibit impulsive responding by increasing behavioral control and monitoring, resulting in fewer commission errors (Kuntsi et al., 2014; Newcorn et al., 2001; White et al., 2011; Yurtbaşı et al., 2018).”
BackgroundMethodTamm, L., Dudley, J. A., Karalunas, S. L., Simon, J. O., Maloney, T. C., Atluri, G., & Epstein, J. N. (2025) · NeuroImage: Reports · doi:10.1016/j.ynirp.2025.100263 · Cited by 4
“Additionally, RTV is highly heritable (Kuntsi et al., 2014).”
Chen, X., Wang, S., Yang, X., Yu, C., Ni, F., Yang, J., Tian, Y., Ye, J., Liu, H., Chen, X., et al. (2026) · Psychology Research and Behavior Management · doi:10.2147/prbm.s550150 · Cited by 4
Bidirectional associations between video game playing and ADHD symptoms among school-aged children
Tiraboschi, G. A., Fitzpatrick, C., Kim, H. S. A., Superbia-Guimarães, L., Kosak, L.-A., & Garon‐Carrier, G. (2025) · Computers in Human Behavior Reports · doi:10.1016/j.chbr.2025.100740 · Cited by 4
Behavior, neuropsychology and fMRI
Bennett, M. R., Hatton, S. N., Hermens, D. F., & Lagopoulos, J. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.07.001 · Cited by 5
Dolan, C. V., de Zeeuw, E. L., Zayats, T., van Beijsterveldt, C. E. M., & Boomsma, D. I. (2020) · Behavior Genetics · doi:10.1007/s10519-020-10002-2 · Cited by 5
Micalizzi, L., Brick, L. A. D., Marraccini, M. E., Benca‐Bachman, C. E., Palmer, R. H. C., & Knopik, V. S. (2020) · Development and Psychopathology · doi:10.1017/s0954579419001573 · Cited by 4
“This finding is not consistent with a study of young twins that determined that the association among inattention and two aspects of neurocognitive functioning (reaction time variability and commission errors) was, in part, attributable to common additive genetic effects (Kuntsi et al., 2014).”
BackgroundResultClinical practice guidelines on cognitive impairment and ADHD-Assessment and Management
Malhotra, S., Kishore, M. T., & Sousa, A. D. (2025) · Indian Journal of Psychiatry · doi:10.4103/indianjpsychiatry.indianjpsychiatry_720_24 · Cited by 3
Genetic variance in conscientiousness relates to youth psychopathology beyond executive functions.
Shields, A. N., Malanchini, M., Vinnik, L., Tucker–Drob, E. M., Harden, K. P., & Tackett, J. L. (2022) · Journal of Psychopathology and Clinical Science · doi:10.1037/abn0000781 · Cited by 3
Bijnens, A., & Pistono, A. (2025) · Speech Communication · doi:10.1016/j.specom.2025.103244 · Cited by 5
Genetic factors and the brain in ADHD
Bralten, J. (2015) · Radboud Repository (Radboud University) · Cited by 3
Knyspel, J., Morneau‐Vaillancourt, G., & Eley, T. C. (2024) · Behavior Genetics · doi:10.1007/s10519-024-10204-y · Cited by 2
Adult ADHD: Future Directions for Practice and Research
Pallanti, S., & Salerno, L. (2020) · Springer eBooks · doi:10.1007/978-3-030-39051-8_20 · Cited by 2
Developmental perspectives on ADHD, treatment implications, and achieving good outcomes
Coghill, D., & Seth, S. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-819749-3.00009-9 · Cited by 1
Pollock, B. E. (2014) · Cited by 1
Attention-deficit/hyperactivity disorder
Klein, M. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-85654-6.00029-0 · Cited by 1
Gennatas, E. D., Wren-Jarvis, J., Powers, R., Lazerwitz, M. C., Bourla, I., Cai, L. T., Choi, H. L., Chu, R., Trimarchi, K. J., Garcia, R. D., et al. (2024) · Imaging Neuroscience · doi:10.1162/imag_a_00076 · Cited by 1
“…with ADHD show gray matter (GM) and white matter (WM) differences from typically developing children ( Hoogman et al., 2019); however, findings are largely divergent ( Pereira-Sanchez & Castellanos, 2021), in major part due to clinical heterogeneity of the ADHD phenotype ( Kuntsi et al., 2014).”
BackgroundAin, Y., Rai, S., Galbraith, A., Buerkner, J., Andrews‐Hanna, J. R., Callahan, B. L., & Kam, J. W. Y. (2025) · Journal of Attention Disorders · doi:10.1177/10870547251394173 · Cited by 1
“…between the genetic determinants and functional outcomes associated with both inattention and hyperactivity-impulsivity symptom dimensions of ADHD (Kuntsi et al., 2014), and researchers have highlighted the need for more studies contrasting the developmental, etiological, and psychological…”
Rodriguez, P. D., & Stauffacher, J. E. (2022) · Midwest Social Sciences Journal · doi:10.22543/2766-0796.1061
“Given the lack of consensus on diagnosing subtypes for ADHD (Kuntsi et al. 2014; Lee et al. 2016), the differential behavioral results in ADHD literature, and the need for further investigation of neural correlates underlying the disorder (Silk et al. 2016), it is crucial that the neural basis of…”
BackgroundGreen, B. C. (2018) · Minerva Access (University of Melbourne) · Cited by 1
Meeuwsen, M. (2015) · ORCA Online Research @Cardiff (Cardiff University)
Asherson, P. J., Buitelaar, J. K., Faraone, S. V., Jebsen, K. G., & Rohde, L. A. (2016)
Self-citationMarley, C. (2019) · The University of Queensland · doi:10.14264/uql.2019.176 · Cited by 1
Maheswary, K. U., & Priya, S. M. (2020) · Springer eBooks · doi:10.1007/978-3-030-41862-5_173
Maema, E. K. (2021) · Unisa Institutional Repository (University of South Africa)
(2019) · Emerald Group Publishing Limited eBooks · doi:10.1108/978-1-83867-895-120191002
(2022) · Midwest Social Sciences Journal · doi:10.22543/2766-0796.1103
Kawichai, T., Plaimas, K., & Suratanee, A. (2019) · doi:10.58837/chula.the.2020.1358
Metadata
- Authors
- Kuntsi, J., Pinto, R., Price, T. S., van der Meere, J. J., Frazier-Wood, A. C., & Asherson, P.
- Affiliations
- King's College London (GB)
- Corresponding author
- Kuntsi, Jonna
- Venue
- Journal of Abnormal Child Psychology
- Published
- 2013-07-10
- Volume
- 42
- Issue
- 1
- Pages
- 127-136
- ISSN
- 0091-0627 (ISSN-L)
- 1573-2835
- PMC
- PMC4520068
- OpenAlex
- W2012675790
- Cited by
- 106
- References
- 46
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 9 · 2023: 6 · 2022: 8 · 2021: 10 · 2020: 13 · 2019: 8 · 2018: 13 · 2017: 1 · 2016: 11 · 2015: 9 · 2014: 9
- FWCI
- 6.84
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Research on Child and Adolescent Psychopathology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Research Portal (King's College London) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- Wellcome Trust (GR070345MF, 070345)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- attention deficit hyperactivity disorder, inattention, hyperactivity/impulsivity, genetic correlation, reaction time variability, commission errors, cognitive impairment, twin studies, children, go/no-go task
- MeSH terms
- Attention, Attention Deficit Disorder with Hyperactivity, Child, Cognition Disorders, Female, Humans, Impulsive Behavior, Male, Psychiatric Status Rating Scales, Reaction Time, Risk Factors, Twins, Comorbidity, Multivariate Analysis, Genetic Predisposition to Disease
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