Infant Visual Brain Development and Inherited Genetic Liability in Autism

Jessica B. Girault, Kevin Donovan, Zoe Hawks, Muhamed Talovic, Elizabeth Forsen, Jed T. Elison, Mark D. Shen, Meghan R. Swanson, Jason J. Wolff, Sun Hyung Kim, Tomoyuki Nishino, Savannah Davis, Abraham Z. Snyder, Kelly N. Botteron, Annette M. Estes, Stephen R. Dager, Heather C. Hazlett, Guido Gerig, Robert McKinstry, Juhi PandeyRobert T. Schultz, Tanya St John, Lonnie Zwaigenbaum, Alexandre Todorov, Young Truong, Martin Styner, John R. Pruett, John N. Constantino, Joseph Piven

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Objective: Autism spectrum disorder (ASD) is heritable, and younger siblings of ASD probands are at higher likelihood of developing ASD themselves. Prospective MRI studies of siblings report that atypical brain development precedes ASD diagnosis, although the link between brain maturation and genetic factors is unclear.Given that familial recurrence of ASD is predicted by higher levels of ASD traits in the proband, the authors investigated associations between proband ASD traits and brain development among younger siblings. Methods: In a sample of 384 proband-sibling pairs (89 pairs concordant for ASD), the authors examined associations between proband ASD traits and sibling brain development at 6, 12, and 24 months in key MRI phenotypes: total cerebral volume, cortical surface area, extra-axial cerebrospinal fluid, occipital cortical surface area, and splenium white matter microstructure. Results from primary analyses led the authors to implement a data-driven approach using functional connectivity MRI at 6 months. Results: Greater levels of proband ASD traits were associated with larger total cerebral volume and surface area and larger surfaceareaandreducedwhitematter integrityincomponents ofthevisual systeminsiblingswhodevelopedASD.Thisaligned withweaker functional connectivitybetween several networks and the visual system among all siblings during infancy. Conclusions: The findings provide evidence that specific early brain MRI phenotypes of ASD reflect quantitative variation in familial ASD traits. Multimodal anatomical and functional convergence on cortical regions, fiber pathways, and functional networks involved in visual processing suggest that inherited liability has a role in shaping the prodromal development of visual circuitry in ASD.

    Original languageEnglish (US)
    Pages (from-to)573-585
    Number of pages13
    JournalAmerican Journal of Psychiatry
    Volume179
    Issue number8
    DOIs
    StatePublished - Aug 2022

    ASJC Scopus subject areas

    • Psychiatry and Mental health

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