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The Separation of ADHD Inattention and Hyperactivity-Impulsivity Symptoms: Pathways from Genetic Effects to Cognitive Impairments and Symptoms
Open accessAbstract
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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MethodHalperin, J. M., Trampush, J. W., Miller, C. J., Marks, D. J., & Newcorn, J. H. (2008) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2008.01926.x · Cited by 252 · cited 5×
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Reaction time performance in ADHD: improvement under fast-incentive condition and familial effects
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“sensitive improvement in RTV (for example under rewarded conditions (Andreou et al. 2007; Kuntsi et al. 2009; Uebel et al. 2010)), measure largely the same etiological process as RTVunder baseline condition (Kuntsi et al.”
InfluentialSelf-citationChen, W., Zhou, K., Sham, P., Franke, B., Kuntsi, J., Campbell, D., Fleischman, K., Knight, J., Andreou, P., Arnold, R., et al. (2008) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30672 · Cited by 173 · cited 1×
“The similarity between the findings presented here and the previous study using clinical cases of ADHD provides further evidence that ADHD reflects the extreme and impairing tail of quantitative traits for inattention and hyperactivity-impulsivity (Chen et al. 2008).”
ResultSelf-citationTodd, R. D., Rasmussen, E. R., Neuman, R. J., Reich, W., Hudziak, J. J., Bucholz, K. K., Madden, P. A. F., & Heath, A. C. (2001) · American Journal of Psychiatry · doi:10.1176/appi.ajp.158.11.1891 · Cited by 165 · cited 1×
“Empirical approaches to ADHD subtypes indicate that many inattentive subtype cases reflect sub-threshold combined type ADHD and should not be treated as a separate category (Todd et al. 2001).”
BackgroundKuntsi, 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., et al. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2010.139 · Cited by 162 · cited 20×
“Secondly, we examine whether the etiological separation between impaired RT performance and CE (Kuntsi et al. 2010) is confirmed in a population twin sample.”
InfluentialSelf-citationUebel, H., Albrecht, B., Asherson, P., Börger, N. A., Butler, L., Chen, W., Christiansen, H., Heise, A., Kuntsi, J., Schäfer, U., et al. (2010) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2009.02139.x · Cited by 161 · cited 4×
“2010a) were similar to those observed in a large clinical sample of ADHD combined subtype cases (Andreou et al. 2007; Kuntsi et al. 2010; Uebel et al. 2010; Wood et al. 2010b).”
InfluentialSelf-citationMultivariate Genetic Analysis of Sex Limitation and G × E Interaction
Neale, M. C., Røysamb, E., & Jacobson, K. C. (2006) · Twin Research and Human Genetics · doi:10.1375/183242706778024937 · Cited by 144 · cited 3×
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“…found that a general combined factor with separable inattention and hyperactivity-impulsivity dimensions best explained the symptom data (Toplak et al. 2009); a pattern of findings that is reflected in the shared and unique genetic effects that influence inattention and…”
McLoughlin, G., Ronald, A., Kuntsi, J., Asherson, P. J., & Plomin, R. J. (2007) · Research on Child and Adolescent Psychopathology · doi:10.1007/s10802-007-9149-9 · Cited by 130 · cited 2×
“…analyses on ADHD symptom scores indicate that 55–80 % of the genetic influences on inattention also influence hyperactive-impulsivity, with the remaining genetic influences reflecting those that are unique to each symptom domain (Greven et al. 2011; McLoughlin et al. 2007, 2011;Wood et al. 2009).”
Self-citationKUNTSI, J., ROGERS, H., SWINARD, G., BÖRGER, N., MEERE, J. V. D., RIJSDIJK, F., & ASHERSON, P. (2006) · Psychological Medicine · doi:10.1017/s0033291706008580 · Cited by 126 · cited 3×
“To limit the total number of variables, to create psychometrically robust variables (Kuntsi et al. 2006) and to enable a comparison to our previous findings using the same tasks in a clinically diagnosed sample (Kuntsi et al. 2010), summed scores were obtained across two tasks or conditions as…”
Self-citationSelf-Alert Training: Volitional modulation of autonomic arousal improves sustained attention
O’Connell, R. G., Bellgrove, M. A., Dockree, P. M., Lau, A., Fitzgerald, M., & Robertson, I. H. (2008) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2007.12.018 · Cited by 124
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MethodKuntsi, J., Andreou, P., Ma, J., Börger, N. A., & van der Meere, J. J. (2005) · BMC Psychiatry · doi:10.1186/1471-244x-5-40 · Cited by 107 · cited 2×
“The go/no-go task (Borger and van der Meere 2000; Kuntsi et al. 2005; van der Meere et al. 1995) On each trial, one of two possible stimuli appeared for 300 ms in the middle of the computer screen.”
Self-citationGreven, C. U., Rijsdijk, F. V., & Plomin, R. J. (2010) · Research on Child and Adolescent Psychopathology · doi:10.1007/s10802-010-9451-9 · Cited by 97 · cited 4×
“This degree of separation is notable, given the strong genetic correlation between inattention and hyperactivity symptoms, as reported previously (Greven et al. 2011; McLoughlin et al. 2007, 2011; Paloyelis et al. 2010; Wood et al. 2009) and further confirmed here (ra=0.”
InfluentialTODD, R. D., HUANG, H., TODOROV, A. A., NEUMAN, R. J., REIERSEN, A. M., HENDERSON, C. A., & REICH, W. C. (2008) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/chi.0b013e31815a6aca · Cited by 96 · cited 4×
“Furthermore, hyperactivityimpulsivity decreases relative to inattention throughout development in both clinical (Biederman et al. 2000; Todd et al. 2008) and population (Larsson et al. 2006) samples.”
InfluentialPaloyelis, Y., Rijsdijk, F. V., Wood, A. C., Asherson, P. J., & Kuntsi, J. (2010) · Research on Child and Adolescent Psychopathology · doi:10.1007/s10802-010-9429-7 · Cited by 91 · cited 2×
“For example, reading difficulties are linked predominantly to inattention (Paloyelis et al. 2010; Willcutt et al. 2007), and oppositional behaviours to hyperactivity-impulsivity (Newcorn et al. 2001; Wood et al. 2009).”
Self-citationKUNTSI, J., WOOD, A. C., VAN DER MEERE, J., & ASHERSON, P. (2009) · Journal of the International Neuropsychological Society · doi:10.1017/s135561770909081x · Cited by 80 · cited 5×
“…we previously found that associations between ADHD symptoms and the cognitive impairments of slow and variable RTs and commission errors (CE) (Kuntsi et al. 2009; Wood et al. 2010a) were similar to those observed in a large clinical sample of ADHD combined subtype cases (Andreou et al. 2007;…”
InfluentialSelf-citationAdams, Z. W., Derefinko, K. J., Milich, R. S., & Fillmore, M. T. (2008) · Developmental Disabilities Research Reviews · doi:10.1002/ddrr.37 · Cited by 76 · cited 1×
“A more strictly defined pure inattentive subtype was, however, linked to early attentional problems and inconsistent performance, whereas inhibition difficulties were observed across ADHD subgroups (Adams et al. 2008; Carr et al. 2010).”
BackgroundWood, A. C., Rijsdijk, F. V., Johnson, K. A., Andreou, P., Albrecht, B., Vásquez, A. A., Buitelaar, J. K., McLoughlin, G., Rommelse, N. N. J., Sergeant, J. A., et al. (2010) · Psychological Medicine · doi:10.1017/s003329171000108x · Cited by 74 · cited 4×
“Our findings also confirm the previous observation (Wood et al. 2010a) that MRT indexes largely the same genetic liability as RTV, observed in the high additive genetic correlation of 0.87.”
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“The go/no-go task (Borger and van der Meere 2000; Kuntsi et al. 2005; van der Meere et al. 1995) On each trial, one of two possible stimuli appeared for 300 ms in the middle of the computer screen.”
Wood, A. C., Asherson, P. J., van der Meere, J. J., & Kuntsi, J. (2009) · Psychological Medicine · doi:10.1017/s003329170999119x · Cited by 67 · cited 4×
“Our findings also confirm the previous observation (Wood et al. 2010a) that MRT indexes largely the same genetic liability as RTV, observed in the high additive genetic correlation of 0.87.”
InfluentialSelf-citationCognitive Control and Attentional Selection in Adolescents with ADHD Versus ADD
Carr, L., Henderson, J., & Nigg, J. T. (2010) · Journal of Clinical Child & Adolescent Psychology · doi:10.1080/15374416.2010.517168 · Cited by 61 · cited 2×
“A more strictly defined pure inattentive subtype was, however, linked to early attentional problems and inconsistent performance, whereas inhibition difficulties were observed across ADHD subgroups (Adams et al. 2008; Carr et al. 2010).”
BackgroundVisual Behaviour of ADHD Children During an Attention Test: An Almost Forgotten Variable
Börger, N. A., & van der Meere, J. (2000) · Journal of Child Psychology and Psychiatry · doi:10.1111/1469-7610.00637 · Cited by 44
Journal of Child Psychology and Psychiatry
Flouri, E., Tzavidis, N., & Kallis, C. (2010) · Journal of Child Psychology and Psychiatry · doi:10.1111/(issn)1469-7610 · Cited by 41
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“Previous twin analyses on ADHD symptom scores indicate that 55–80 % of the genetic influences on inattention also influence hyperactive-impulsivity, with the remaining genetic influences reflecting those that are unique to each symptom domain (Greven et al. 2011; McLoughlin et al. 2007, 2011;Wood et al. 2009).”
InfluentialSelf-citationMcLoughlin, G., Rijsdijk, F. V., Asherson, P. J., & Kuntsi, J. (2011) · Behavior Genetics · doi:10.1007/s10519-011-9473-2 · Cited by 29 · cited 2×
“…analyses on ADHD symptom scores indicate that 55–80 % of the genetic influences on inattention also influence hyperactive-impulsivity, with the remaining genetic influences reflecting those that are unique to each symptom domain (Greven et al. 2011; McLoughlin et al. 2007, 2011;Wood et al. 2009).”
Self-citationGenetic analysis of reaction time variability: room for improvement?
Kuntsi, J., Wood, A. C., Banaschewski, T., Gill, M., Miranda, A., Oades, R. D., Roeyers, H., Rothenberger, A., Steinhausen, H., van der Meere, J. J., et al. (2012) · Psychological Medicine · doi:10.1017/s0033291712002061 · Cited by 28 · cited 2×
“…improvement in RTV (for example under rewarded conditions (Andreou et al. 2007; Kuntsi et al. 2009; Uebel et al. 2010)), measure largely the same etiological process as RTVunder baseline condition (Kuntsi et al. 2013), supporting theories emphasizing the malleability of the observed high RTV.”
Self-citationVisual Behaviour of ADHD Children During an Attention Test: An Almost Forgotten Variable
Börger, N. A., & van der Meere, J. (2000) · Journal of Child Psychology and Psychiatry · doi:10.1017/s0021963000005655 · Cited by 20
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“processes are both associated with ADHD in children, but are genetically largely uncorrelated, reflecting distinct aetiological pathways (Kuntsi et al., 2014; Kuntsi et al., 2010).”
Self-citation
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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