Neurobehavioral Abnormalities in First-Degree Relatives of Individuals With Autism
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CONTEXT: Studying sensorimotor and neurocognitive impairments in unaffected family members of individuals with autism may help identify familial pathophysiological mechanisms associated with the disorder. OBJECTIVE: To determine whether atypical sensorimotor or neurocognitive characteristics associated with autism are present in first-degree relatives of individuals with autism. DESIGN: Case-control comparison of neurobehavioral functions. SETTING: University medical center. PARTICIPANTS: Fifty-seven first-degree relatives of individuals with autism and 40 age-, sex-, and IQ-matched healthy control participants (aged 8-54 years). MAIN OUTCOME MEASURES: Oculomotor tests of sensorimotor responses (saccades and smooth pursuit); procedural learning and response inhibition; neuropsychological tests of motor, memory, and executive functions; and psychological measures of social behavior, communication skills, and obsessive-compulsive behaviors. RESULTS: On eye movement testing, family members demonstrated saccadic hypometria, reduced steady-state pursuit gain, and a higher rate of voluntary response inhibition errors relative to controls. They also showed lateralized deficits in procedural learning and open-loop pursuit gain (initial 100 milliseconds of pursuit) and increased variability in the accuracy of large-amplitude saccades that were confined to rightward movements. In neuropsychological studies, only executive functions were impaired relative to those of controls. Family members reported more communication abnormalities and obsessive-compulsive behaviors than controls. Deficits across oculomotor, neuropsychological, and psychological domains were relatively independent from one another. CONCLUSIONS: Family members of individuals with autism demonstrate oculomotor abnormalities implicating pontocerebellar and frontostriatal circuits and left-lateralized alterations of frontotemporal circuitry and striatum. The left-lateralized alterations have not been identified in other neuropsychiatric disorders and are of interest given atypical brain lateralization and language development associated with the disorder. Similar oculomotor deficits have been reported in individuals with autism, suggesting that they may be familial and useful for studies of neurophysiological and genetic mechanisms in autism.
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Recent findings that oculomotor deficits in AD are also present in unaffected family members suggest dysfunctions within oculomotor vermis may be familial and could serve as intermediate phenotypes for gene discovery.
“Our recent findings that oculomotor deficits observed in individuals with AD also are present in unaffected family members suggest that dysfunctions within the oculomotor vermis may be familial and could serve as intermediate phenotypes for gene discovery [204].”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [204]
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Self-citationUnruh, K. E., McKinney, W. S., Bojanek, E. K., Fleming, K., Sweeney, J. A., & Mosconi, M. W. (2021) · Figshare · doi:10.6084/m9.figshare.14954697
Self-citationUnruh, K. E., McKinney, W. S., Bojanek, E. K., Fleming, K., Sweeney, J. A., & Mosconi, M. W. (2021) · Figshare · doi:10.6084/m9.figshare.14954691
Self-citationYoshimura, S., Kobayashi, K., Ueno, T., Miyagi, T., Oishi, N., Murai, T., & Fujiwara, H. (2020) · Figshare · doi:10.6084/m9.figshare.13279280
- Authors
- Mosconi, M. W., Kay, M., D’Cruz, A.-M., Guter, S., Kapur, K., Macmillan, C., Stanford, L. D., & Sweeney, J. A.
- Affiliations
- University of Illinois Chicago (US)
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2010-08-01
- Volume
- 67
- Issue
- 8
- Pages
- 830
- ISSN
- 0003-990X (ISSN-L)
- PMC
- PMC3145411
- OpenAlex
- W2122281609
- Cited by
- 84
- References
- 108
- Citations by year
- 2025: 4 · 2023: 2 · 2022: 5 · 2021: 10 · 2020: 7 · 2019: 4 · 2018: 3 · 2017: 6 · 2016: 6 · 2015: 5 · 2014: 6 · 2013: 11 · 2012: 9
- FWCI
- 5.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- KU ScholarWorks (The University of Kansas) (submittedVersion, other-oa)
- Funders
- Autism Speaks (AS6337, AS4853)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P50HD055751, P01HD035469, HD35469, U19HD035469)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- autism spectrum disorder, first-degree relatives, familial aggregation, eye movement disorders, saccades, smooth pursuit eye movements, response inhibition, procedural learning, executive function, hemispheric lateralization, striatum, obsessive-compulsive behavior, social behavior, neurobehavioral abnormalities
- MeSH terms
- Adolescent, Adult, Autistic Disorder, Brain, Child, Eye Movements, Family, Female, Humans, Functional Laterality, Male, Middle Aged, Neuropsychological Tests, Obsessive-Compulsive Disorder, Pursuit, Smooth, Saccades, Ocular Motility Disorders, Case-Control Studies, Executive Function
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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