A review on cognitive and brain endophenotypes that may be common in autism spectrum disorder and attention-deficit/hyperactivity disorder and facilitate the search for pleiotropic genes
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We propose to bring together the hitherto rather separate research fields of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), and argue that by contrasting and combining findings of the endophenotypes of ASD and ADHD new insights can be gained into the etiology and pathophysiology of these two disorders. Given the highly heritable nature of both disorders, studies of the genes explaining the shared origins of the two neurodevelopmental disorders seem particularly called for. Instead of the clinical diagnosis, using neurocognitive measures as (endo)phenotypes that index genetic liability appears a powerful tool in gene finding. We, therefore, extensively reviewed the literature and not only included research wherein ASD and ADHD were compared within a single study, but extended our search also to the separate lines of cognitive neuroscience research. We discuss which cognitive and brain measures will be useful in future genetic studies targeting pleiotropic genes for ASD and ADHD. By specifying the most promising endophenotypic measures we chart the future course for endophenotypic research in ASD and ADHD. We also discuss the various models that may explain the frequent co-occurrence of ASD and ADHD.
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There is growing evidence that ASD and ADHD share common genetic variants, similar psychological deficits and neuroimaging differences.
“There is also growing evidence that ASD and ADHD share common genetic variants, similar psychological deficits and neuroimaging differences [10–12].”
From Mental, behavioral and neurodevelopmental disorders in the ICD-11: an international perspective on key changes and controversies (2020) · cites this paper as [11]
Section 5.4 reports similar executive-function deficits, and section 6 describes similarities in functional and structural brain measures. Sections 1 and 6 also describe evidence of partly shared genetic factors, but they do not establish the more specific claim that ASD and ADHD share common genetic variants. (LLM, conf=0.83)
Experimental — accuracy not yet measuredMany people with ASD often exhibit impairment in the EF domain, although different studies have reached mixed conclusions on the type of affected function.
“however, it should be noted that many people with ASD often exhibit an impairment in the EF domain [8,9], although different studies have reached mixed conclusions on the type of affected function.”
From Comparing Executive Functions in Children and Adolescents with Autism and ADHD—A Systematic Review and Meta-Analysis (2024) · cites this paper as [9]
Individuals with ADHD and ASD are more alike in their executive function difficulties than they are different.
“They concluded that individuals with ADHD and ASD “are more alike in their EF difficulties than they are different” [9] (p. 1377).”
From Comparing Executive Functions in Children and Adolescents with Autism and ADHD—A Systematic Review and Meta-Analysis (2024) · cites this paper as [9]
Considering the executive function domain, ADHD and ADHD+ASD share several commonalities, not only on the behavioral level but also on the neuro-functional level.
“This finding supports other research lines [9,26], stating that, considering the EF domain, ADHD and ADHD+ASD share several commonalities, not only on the behavioral level but also on the neuro-functional level.”
From Comparing Executive Functions in Children and Adolescents with Autism and ADHD—A Systematic Review and Meta-Analysis (2024) · cites this paper as [9]
EF deficits are the neuropsychological traits common to both ADHD and ASD that have received the most support in the literature.
“EF deficits are the neuropsychological traits common to both disorders that have received the most support in the literature”
From Social Cognition in Children with High-Functioning Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder. Associations with Executive Functions (2017) · cites this paper as Rommelse et al., 2011
Siblings of participants with ADHD have a two- to eight-fold elevated risk of ADHD relative to control participants.
“Siblings of participants with ADHD, who share on average 50% of their genetic information, have a two- to eight-fold elevated risk of ADHD relative to control participants22.”
From Increased neural responses to reward in adolescents and young adults with attention-deficit/hyperactivity disorder and their unaffected siblings (2015) · cites this paper as [22]
Section 1 (“ASD and ADHD”) reports that ADHD is strongly heritable, and sections 5.7–5.8 discuss traits in siblings of people with ADHD. None of these passages gives siblings’ risk of an ADHD diagnosis relative to controls. Searches for the two- to eight-fold figure and sibling ADHD risk found no passage establishing that comparison. (LLM, conf=0.72)
Experimental — accuracy not yet measuredPoor social skills, language delay, sensory overresponsivity, attention problems, oppositional defiant behavior, and emotion regulation problems are frequently present in both ASD and ADHD.
“Features such as poor social skills, language delay, sensory overresponsivity, attention problems, oppositional defiant behavior, and emotion regulation problems are frequently disclosed in both ASD and ADHD.[5][6][7]”
Because previous studies used DSM-IV defined heterogeneous groups and ADHD was not always assessed in ASD children, group comparisons may have been significantly obscured.
“However, because these studies used DSM-IV defined (hence heterogeneous) groups of patients and because ADHD was not always assessed in children with ASD, 7 group comparisons may have been significantly obscured.”
ASD patients showed some degree of performance impairment, in line with evidence for more severe attention deficits in ADHD than ASD.
“Only for some of the longer delays, ASD patients also showed slower reaction times, suggesting some degree of performance impairment, in line with evidence for more severe attention deficits in ADHD than ASD.12, 50”
From Disorder-specific functional abnormalities during sustained attention in youth with Attention Deficit Hyperactivity Disorder (ADHD) and with Autism (2013) · cites this paper as [50]
Similar neuropsychological profiles among individuals with ADHD and ASD provide evidence for common neurobiological substrates.
“evidence for common neurobiological substrates has been found through similarities in neuropsychological profiles among individuals with ADHD and ASD [11,17].”
From Treatment for Co-Occurring Attention Deficit/Hyperactivity Disorder and Autism Spectrum Disorder (2012) · cites this paper as [17]
Interest in the co-occurrence of ADHD and ASD has grown tremendously in the last decade, with multiple published studies addressing heritability and shared etiology, as well as common phenotypic and endophenotypic features.
“Interest in the co-occurrence of ADHD and ASD has grown tremendously in the last decade, with multiple published studies addressing questions of heritability and shared etiology [13,15,124], as well as common phenotypic and endophenotypic features [17,42].”
From Treatment for Co-Occurring Attention Deficit/Hyperactivity Disorder and Autism Spectrum Disorder (2012) · cites this paper as [17]
The current findings further highlight that fronto-striato-parietal aberrations may underlie the shared ASD-ADHD clinical phenotype, including executive and motivation dysfunction.
“In sum, the current findings further highlight that fronto-striato-parietal aberrations may underlie the shared ASD-ADHD clinical phenotype, including executive and motivation dysfunction; both domains constitute the most consistent cognitive deficits among the two disorders (Rommelse et al., 2011).”
From Differentiating neural reward responsiveness in autism versus ADHD (2014) · cites this paper as Rommelse et al., 2011
Based on available literature and current neurobiological models, it is plausible to assume that reward-based motivation deficits may lie at the core of both ASD and ADHD.
“Although no direct link between brain dysfunction and clinical manifestation could be revealed, based on the available literature and current neurobiological models (Rommelse et al., 2011, Taurines et al., 2012), it is plausible to assume that reward-based motivation deficits may lie at the core of both ASD and ADHD (Dichter et al., 2012a).”
From Differentiating neural reward responsiveness in autism versus ADHD (2014) · cites this paper as Rommelse et al., 2011
ADHD symptoms are very common among youth with ASD, making our ASD sample representative for this clinical disorder.
“However, ADHD symptoms are very common among youth with ASD (Rommelse et al., 2011), making our ASD sample representative for this clinical disorder.”
From Differentiating neural reward responsiveness in autism versus ADHD (2014) · cites this paper as Rommelse et al., 2011
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Weighted Fourier Series Representation and Its Application to Quantifying the Amount of Gray Matter
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Abnormal cerebral cortex structure in children with ADHD
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Endophenotypes in psychiatric genetics
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Cortical Anatomy in Autism Spectrum Disorder: An In Vivo MRI Study on the Effect of Age
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Atypical involvement of frontostriatal systems during sensorimotor control in autism
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Current Status of Cognitive Behavioral Therapy for Adult Attention-Deficit Hyperactivity Disorder
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Functional Effects of the DAT1 Polymorphism on EEG Measures in ADHD
Loo, S. K., SPECTER, E., Smolen, A., Hopfer, C. J., Teale, P. D., & Reite, M. L. (2003) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/01.chi.0000046890.27264.88 · Cited by 169 · see citing works
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Sleep Patterns in Preschool-Age Children With Autism, Developmental Delay, and Typical Development
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Genetics of attention deficit hyperactivity disorder
Faraone, S. V., & Larsson, H. (2019) · Molecular Psychiatry · doi:10.1038/s41380-018-0070-0 · Cited by 1,338 · see citing works
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Live fast, die young? A review on the developmental trajectories of ADHD across the lifespan
Franke, B., Michelini, G., Asherson, P., Banaschewski, T., Bilbow, A., Buitelaar, J. K., Cormand, B., Faraone, S. V., Ginsberg, Y., Haavik, J., et al. (2018) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2018.08.001 · Cited by 643 · see citing works
Self-citationDevelopmental pathways to autism: A review of prospective studies of infants at risk
Jones, E. J. H., Gliga, T., Bedford, R., Charman, T., & Johnson, M. H. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.12.001 · Cited by 607 · see citing works
Leitner, Y. (2014) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2014.00268 · Cited by 439 · see citing works
“Evidence for common neurobiological substrates has been found through similarities in neuropsychological profiles in individuals with both disorders (Gargaro et al., 2011; Rommelse et al., 2011).”
The genetics of attention deficit/hyperactivity disorder in adults, a review
on behalf of the International Multicentre persistent ADHD CollaboraTion (IMpACT), Franke, B., Faraone, S. V., Asherson, P., Buitelaar, J., Bau, C. H. D., Ramos-Quiroga, J. A., Mick, E., Grevet, E. H., Johansson, S., et al. (2012) · Molecular Psychiatry · doi:10.1038/mp.2011.138 · Cited by 432 · see citing works
Self-citationAnnual Research Review: The transdiagnostic revolution in neurodevelopmental disorders
Astle, D. E., Holmes, J., Kievit, R., & Gathercole, S. E. (2022) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.13481 · Cited by 384 · see citing works
Di Martino, A., Zuo, X.-N., Kelly, C., Grzadzinski, R., Mennes, M., Schvarcz, A., Rodman, J., Lord, C., Castellanos, F. X., & Milham, M. P. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.02.011 · Cited by 345 · see citing works
Rong, Y., Yang, C.-J., Jin, Y., & Wang, Y. (2021) · Research in Autism Spectrum Disorders · doi:10.1016/j.rasd.2021.101759 · Cited by 316 · see citing works
van der Meer, J. M. J., Oerlemans, A. M., van Steijn, D. J., Lappenschaar, M. G. A., de Sonneville, L. M. J., Buitelaar, J. K., & Rommelse, N. N. J. (2012) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2012.08.024 · Cited by 303 · see citing works
Self-citationADHD and autism: differential diagnosis or overlapping traits? A selective review
Taurines, R., Schwenck, C., Westerwald, E., Sachse, M., Siniatchkin, M., & Freitag, C. (2012) · ADHD Attention Deficit and Hyperactivity Disorders · doi:10.1007/s12402-012-0086-2 · Cited by 301 · see citing works
MRC AIMS consortium, Christakou, A., Murphy, C. M., Chantiluke, K., Cubillo, A. I., Smith, A. B., Giampietro, V, Daly, E., Ecker, C., Robertson, D., et al. (2013) · Molecular Psychiatry · doi:10.1038/mp.2011.185 · Cited by 293 · see citing works
Karalunas, S. L., Geurts, H. M., Konrad, K., Bender, S., & Nigg, J. T. (2014) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.12217 · Cited by 278 · see citing works
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Tye, C., Runicles, A. K., Whitehouse, A. J. O., & Alvares, G. A. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2018.00751 · Cited by 177 · see citing works
Maternal Smoking and Attention-Deficit/Hyperactivity Disorder in Offspring: A Meta-analysis
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Treatment for Co-Occurring Attention Deficit/Hyperactivity Disorder and Autism Spectrum Disorder
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Karalunas, S. L., Hawkey, E., Gustafsson, H., Miller, M., Langhorst, M., Cordova, M., Fair, D., & Nigg, J. T. (2018) · Journal of Abnormal Child Psychology · doi:10.1007/s10802-017-0394-2 · Cited by 148 · see citing works
“However, our results suggest important amendments to the shared liability proposal for RT measures (Rommelse et al. 2011).”
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Sokolova, E., Oerlemans, A. M., Rommelse, N. N., Groot, P., Hartman, C. A., Glennon, J. C., Claassen, T., Heskes, T., & Buitelaar, J. K. (2017) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-017-3083-7 · Cited by 136 · see citing works
Self-citationDoes neurocognitive functioning predict future or persistence of ADHD? A systematic review
van Lieshout, M., Luman, M., Buitelaar, J., Rommelse, N. N. J., & Oosterlaan, J. (2013) · Clinical Psychology Review · doi:10.1016/j.cpr.2013.02.003 · Cited by 133 · see citing works
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Hartman, C. A., Geurts, H. M., Franke, B., Buitelaar, J. K., & Rommelse, N. N. J. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.09.003 · Cited by 111 · see citing works
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“In fact, EF deficits are the neuropsychological traits common to both disorders that have received the most support in the literature (Rommelse et al., 2011), although findings related to the specific subdomains of the deficit are not completely consistent.”
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- Authors
- Rommelse, N. N. J., Geurts, H. M., Franke, B., Buitelaar, J. K., & Hartman, C. A.
- Affiliations
- Radboud University Nijmegen (NL)
- Venue
- Neuroscience & Biobehavioral Reviews
- Publisher
- Elsevier BV
- Published
- 2011-05
- Volume
- 35
- Issue
- 6
- Pages
- 1363-1396
- ISSN
- 0149-7634 (ISSN-L)
- OpenAlex
- W2148396375
- Cited by
- 429
- References
- 396
- Citations by year
- 2026: 12 · 2025: 9 · 2024: 26 · 2023: 29 · 2022: 32 · 2021: 33 · 2020: 32 · 2019: 30 · 2018: 26 · 2017: 21 · 2016: 36 · 2015: 36 · 2014: 47 · 2013: 28 · 2012: 26
- FWCI
- 2.81
- Type
- journal article
- Language
- en
- Open access
- green
- research.rug.nl
- Licence
- Locations
- Neuroscience & Biobehavioral Reviews (publishedVersion)
- PubMed (publishedVersion)
- UvA-DARE (University of Amsterdam) (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- UvA-DARE (University of Amsterdam) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- autism spectrum disorder, attention deficit hyperactivity disorder, endophenotypes, pleiotropic genes, neurocognitive measures, genetic susceptibility, neurodevelopmental disorders, etiology and pathophysiology, gene discovery
- MeSH terms
- Attention Deficit Disorder with Hyperactivity, Brain, Child, Child Development Disorders, Pervasive, Cognition, Humans, Endophenotypes, Genetic Pleiotropy
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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.
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