Language delay aggregates in toddler siblings of children with autism spectrum disorder

N. Marrus, L. P. Hall, S. J. Paterson, J. T. Elison, J. J. Wolff, M. R. Swanson, J. Parish-Morris, A. T. Eggebrecht, J. R. Pruett, H. C. Hazlett, L. Zwaigenbaum, S. Dager, A. M. Estes, R. T. Schultz, K. N. Botteron, J. Piven, J. N. Constantino, J. Piven, H. C. Hazlett, C. ChappellS. Dager, A. Estes, D. Shaw, K. Botteron, R. McKinstry, J. Constantino, J. Pruett, R. T. Schultz, S. Paterson, L. Zwaigenbaum, J. Elison, A. C. Evans, D. L. Collins, G. B. Pike, V. Fonov, P. Kostopoulos, S. Das, Guido Gerig, M. Styner, H. Gu

    Research output: Contribution to journalArticle

    Abstract

    Background: Language delay is extremely common in children with autism spectrum disorder (ASD), yet it is unclear whether measurable variation in early language is associated with genetic liability for ASD. Assessment of language development in unaffected siblings of children with ASD can inform whether decreased early language ability aggregates with inherited risk for ASD and serves as an ASD endophenotype. Methods: We implemented two approaches: (1) a meta-analysis of studies comparing language delay, a categorical indicator of language function, and language scores, a continuous metric, in unaffected toddlers at high and low familial risk for ASD, and (2) a parallel analysis of 350 unaffected 24-month-olds in the Infant Brain Imaging Study (IBIS), a prospective study of infants at high and low familial risk for ASD. An advantage of the former was its detection of group differences from pooled data across unique samples; an advantage of the latter was its sensitivity in quantifying early manifestations of language delay while accounting for covariates within a single large sample. Results: Meta-analysis showed that high-risk siblings without ASD (HR-noASD) were three to four times more likely to exhibit language delay versus low-risk siblings without ASD (LR-noASD) and had lower mean receptive and expressive language scores. Analyses of IBIS data corroborated that language delay, specifically receptive language delay, was more frequent in the HR-noASD (n = 235) versus LR-noASD group (n = 115). IBIS language scores were continuously and unimodally distributed, with a pathological shift towards decreased language function in HR-noASD siblings. The elevated inherited risk for ASD was associated with lower receptive and expressive language scores when controlling for sociodemographic factors. For receptive but not expressive language, the effect of risk group remained significant even when controlling for nonverbal cognition. Conclusions: Greater frequency of language delay and a lower distribution of language scores in high-risk, unaffected toddler-aged siblings support decreased early language ability as an endophenotype for ASD, with a more pronounced effect for receptive versus expressive language. Further characterization of language development is warranted to refine genetic investigations of ASD and to elucidate factors influencing the progression of core autistic traits and related symptoms.

    Original languageEnglish (US)
    Article number29
    JournalJournal of Neurodevelopmental Disorders
    Volume10
    Issue number1
    DOIs
    StatePublished - Oct 22 2018

    Fingerprint

    Language Development Disorders
    Siblings
    Language
    Neuroimaging
    Endophenotypes
    Language Development
    Aptitude
    Meta-Analysis
    Autism Spectrum Disorder
    Cognition

    Keywords

    • Autism spectrum disorder
    • Development
    • Endophenotype
    • Infant sibling
    • Language

    ASJC Scopus subject areas

    • Pediatrics, Perinatology, and Child Health
    • Pathology and Forensic Medicine
    • Clinical Neurology
    • Cognitive Neuroscience

    Cite this

    Marrus, N., Hall, L. P., Paterson, S. J., Elison, J. T., Wolff, J. J., Swanson, M. R., ... Gu, H. (2018). Language delay aggregates in toddler siblings of children with autism spectrum disorder. Journal of Neurodevelopmental Disorders, 10(1), [29]. https://doi.org/10.1186/s11689-018-9247-8

    Language delay aggregates in toddler siblings of children with autism spectrum disorder. / Marrus, N.; Hall, L. P.; Paterson, S. J.; Elison, J. T.; Wolff, J. J.; Swanson, M. R.; Parish-Morris, J.; Eggebrecht, A. T.; Pruett, J. R.; Hazlett, H. C.; Zwaigenbaum, L.; Dager, S.; Estes, A. M.; Schultz, R. T.; Botteron, K. N.; Piven, J.; Constantino, J. N.; Piven, J.; Hazlett, H. C.; Chappell, C.; Dager, S.; Estes, A.; Shaw, D.; Botteron, K.; McKinstry, R.; Constantino, J.; Pruett, J.; Schultz, R. T.; Paterson, S.; Zwaigenbaum, L.; Elison, J.; Evans, A. C.; Collins, D. L.; Pike, G. B.; Fonov, V.; Kostopoulos, P.; Das, S.; Gerig, Guido; Styner, M.; Gu, H.

    In: Journal of Neurodevelopmental Disorders, Vol. 10, No. 1, 29, 22.10.2018.

    Research output: Contribution to journalArticle

    Marrus, N, Hall, LP, Paterson, SJ, Elison, JT, Wolff, JJ, Swanson, MR, Parish-Morris, J, Eggebrecht, AT, Pruett, JR, Hazlett, HC, Zwaigenbaum, L, Dager, S, Estes, AM, Schultz, RT, Botteron, KN, Piven, J, Constantino, JN, Piven, J, Hazlett, HC, Chappell, C, Dager, S, Estes, A, Shaw, D, Botteron, K, McKinstry, R, Constantino, J, Pruett, J, Schultz, RT, Paterson, S, Zwaigenbaum, L, Elison, J, Evans, AC, Collins, DL, Pike, GB, Fonov, V, Kostopoulos, P, Das, S, Gerig, G, Styner, M & Gu, H 2018, 'Language delay aggregates in toddler siblings of children with autism spectrum disorder', Journal of Neurodevelopmental Disorders, vol. 10, no. 1, 29. https://doi.org/10.1186/s11689-018-9247-8
    Marrus, N. ; Hall, L. P. ; Paterson, S. J. ; Elison, J. T. ; Wolff, J. J. ; Swanson, M. R. ; Parish-Morris, J. ; Eggebrecht, A. T. ; Pruett, J. R. ; Hazlett, H. C. ; Zwaigenbaum, L. ; Dager, S. ; Estes, A. M. ; Schultz, R. T. ; Botteron, K. N. ; Piven, J. ; Constantino, J. N. ; Piven, J. ; Hazlett, H. C. ; Chappell, C. ; Dager, S. ; Estes, A. ; Shaw, D. ; Botteron, K. ; McKinstry, R. ; Constantino, J. ; Pruett, J. ; Schultz, R. T. ; Paterson, S. ; Zwaigenbaum, L. ; Elison, J. ; Evans, A. C. ; Collins, D. L. ; Pike, G. B. ; Fonov, V. ; Kostopoulos, P. ; Das, S. ; Gerig, Guido ; Styner, M. ; Gu, H. / Language delay aggregates in toddler siblings of children with autism spectrum disorder. In: Journal of Neurodevelopmental Disorders. 2018 ; Vol. 10, No. 1.
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    abstract = "Background: Language delay is extremely common in children with autism spectrum disorder (ASD), yet it is unclear whether measurable variation in early language is associated with genetic liability for ASD. Assessment of language development in unaffected siblings of children with ASD can inform whether decreased early language ability aggregates with inherited risk for ASD and serves as an ASD endophenotype. Methods: We implemented two approaches: (1) a meta-analysis of studies comparing language delay, a categorical indicator of language function, and language scores, a continuous metric, in unaffected toddlers at high and low familial risk for ASD, and (2) a parallel analysis of 350 unaffected 24-month-olds in the Infant Brain Imaging Study (IBIS), a prospective study of infants at high and low familial risk for ASD. An advantage of the former was its detection of group differences from pooled data across unique samples; an advantage of the latter was its sensitivity in quantifying early manifestations of language delay while accounting for covariates within a single large sample. Results: Meta-analysis showed that high-risk siblings without ASD (HR-noASD) were three to four times more likely to exhibit language delay versus low-risk siblings without ASD (LR-noASD) and had lower mean receptive and expressive language scores. Analyses of IBIS data corroborated that language delay, specifically receptive language delay, was more frequent in the HR-noASD (n = 235) versus LR-noASD group (n = 115). IBIS language scores were continuously and unimodally distributed, with a pathological shift towards decreased language function in HR-noASD siblings. The elevated inherited risk for ASD was associated with lower receptive and expressive language scores when controlling for sociodemographic factors. For receptive but not expressive language, the effect of risk group remained significant even when controlling for nonverbal cognition. Conclusions: Greater frequency of language delay and a lower distribution of language scores in high-risk, unaffected toddler-aged siblings support decreased early language ability as an endophenotype for ASD, with a more pronounced effect for receptive versus expressive language. Further characterization of language development is warranted to refine genetic investigations of ASD and to elucidate factors influencing the progression of core autistic traits and related symptoms.",
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    author = "N. Marrus and Hall, {L. P.} and Paterson, {S. J.} and Elison, {J. T.} and Wolff, {J. J.} and Swanson, {M. R.} and J. Parish-Morris and Eggebrecht, {A. T.} and Pruett, {J. R.} and Hazlett, {H. C.} and L. Zwaigenbaum and S. Dager and Estes, {A. M.} and Schultz, {R. T.} and Botteron, {K. N.} and J. Piven and Constantino, {J. N.} and J. Piven and Hazlett, {H. C.} and C. Chappell and S. Dager and A. Estes and D. Shaw and K. Botteron and R. McKinstry and J. Constantino and J. Pruett and Schultz, {R. T.} and S. Paterson and L. Zwaigenbaum and J. Elison and Evans, {A. C.} and Collins, {D. L.} and Pike, {G. B.} and V. Fonov and P. Kostopoulos and S. Das and Guido Gerig and M. Styner and H. Gu",
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    TY - JOUR

    T1 - Language delay aggregates in toddler siblings of children with autism spectrum disorder

    AU - Marrus, N.

    AU - Hall, L. P.

    AU - Paterson, S. J.

    AU - Elison, J. T.

    AU - Wolff, J. J.

    AU - Swanson, M. R.

    AU - Parish-Morris, J.

    AU - Eggebrecht, A. T.

    AU - Pruett, J. R.

    AU - Hazlett, H. C.

    AU - Zwaigenbaum, L.

    AU - Dager, S.

    AU - Estes, A. M.

    AU - Schultz, R. T.

    AU - Botteron, K. N.

    AU - Piven, J.

    AU - Constantino, J. N.

    AU - Piven, J.

    AU - Hazlett, H. C.

    AU - Chappell, C.

    AU - Dager, S.

    AU - Estes, A.

    AU - Shaw, D.

    AU - Botteron, K.

    AU - McKinstry, R.

    AU - Constantino, J.

    AU - Pruett, J.

    AU - Schultz, R. T.

    AU - Paterson, S.

    AU - Zwaigenbaum, L.

    AU - Elison, J.

    AU - Evans, A. C.

    AU - Collins, D. L.

    AU - Pike, G. B.

    AU - Fonov, V.

    AU - Kostopoulos, P.

    AU - Das, S.

    AU - Gerig, Guido

    AU - Styner, M.

    AU - Gu, H.

    PY - 2018/10/22

    Y1 - 2018/10/22

    N2 - Background: Language delay is extremely common in children with autism spectrum disorder (ASD), yet it is unclear whether measurable variation in early language is associated with genetic liability for ASD. Assessment of language development in unaffected siblings of children with ASD can inform whether decreased early language ability aggregates with inherited risk for ASD and serves as an ASD endophenotype. Methods: We implemented two approaches: (1) a meta-analysis of studies comparing language delay, a categorical indicator of language function, and language scores, a continuous metric, in unaffected toddlers at high and low familial risk for ASD, and (2) a parallel analysis of 350 unaffected 24-month-olds in the Infant Brain Imaging Study (IBIS), a prospective study of infants at high and low familial risk for ASD. An advantage of the former was its detection of group differences from pooled data across unique samples; an advantage of the latter was its sensitivity in quantifying early manifestations of language delay while accounting for covariates within a single large sample. Results: Meta-analysis showed that high-risk siblings without ASD (HR-noASD) were three to four times more likely to exhibit language delay versus low-risk siblings without ASD (LR-noASD) and had lower mean receptive and expressive language scores. Analyses of IBIS data corroborated that language delay, specifically receptive language delay, was more frequent in the HR-noASD (n = 235) versus LR-noASD group (n = 115). IBIS language scores were continuously and unimodally distributed, with a pathological shift towards decreased language function in HR-noASD siblings. The elevated inherited risk for ASD was associated with lower receptive and expressive language scores when controlling for sociodemographic factors. For receptive but not expressive language, the effect of risk group remained significant even when controlling for nonverbal cognition. Conclusions: Greater frequency of language delay and a lower distribution of language scores in high-risk, unaffected toddler-aged siblings support decreased early language ability as an endophenotype for ASD, with a more pronounced effect for receptive versus expressive language. Further characterization of language development is warranted to refine genetic investigations of ASD and to elucidate factors influencing the progression of core autistic traits and related symptoms.

    AB - Background: Language delay is extremely common in children with autism spectrum disorder (ASD), yet it is unclear whether measurable variation in early language is associated with genetic liability for ASD. Assessment of language development in unaffected siblings of children with ASD can inform whether decreased early language ability aggregates with inherited risk for ASD and serves as an ASD endophenotype. Methods: We implemented two approaches: (1) a meta-analysis of studies comparing language delay, a categorical indicator of language function, and language scores, a continuous metric, in unaffected toddlers at high and low familial risk for ASD, and (2) a parallel analysis of 350 unaffected 24-month-olds in the Infant Brain Imaging Study (IBIS), a prospective study of infants at high and low familial risk for ASD. An advantage of the former was its detection of group differences from pooled data across unique samples; an advantage of the latter was its sensitivity in quantifying early manifestations of language delay while accounting for covariates within a single large sample. Results: Meta-analysis showed that high-risk siblings without ASD (HR-noASD) were three to four times more likely to exhibit language delay versus low-risk siblings without ASD (LR-noASD) and had lower mean receptive and expressive language scores. Analyses of IBIS data corroborated that language delay, specifically receptive language delay, was more frequent in the HR-noASD (n = 235) versus LR-noASD group (n = 115). IBIS language scores were continuously and unimodally distributed, with a pathological shift towards decreased language function in HR-noASD siblings. The elevated inherited risk for ASD was associated with lower receptive and expressive language scores when controlling for sociodemographic factors. For receptive but not expressive language, the effect of risk group remained significant even when controlling for nonverbal cognition. Conclusions: Greater frequency of language delay and a lower distribution of language scores in high-risk, unaffected toddler-aged siblings support decreased early language ability as an endophenotype for ASD, with a more pronounced effect for receptive versus expressive language. Further characterization of language development is warranted to refine genetic investigations of ASD and to elucidate factors influencing the progression of core autistic traits and related symptoms.

    KW - Autism spectrum disorder

    KW - Development

    KW - Endophenotype

    KW - Infant sibling

    KW - Language

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