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.
ASJC Scopus subject areas
- Psychiatry and Mental health