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Researchers from the University of California San Diego have found critical insights into the developmental origins of autism spectrum disorder (ASD) and its varying severity levels.

Using inducible pluripotent stem cells (iPSCs) derived from blood samples of 10 toddlers with autism and six neurotypical controls, the researchers created brain cortical organoids (BCOs) to simulate early embryonic brain development. These miniature brain models showed significant overgrowth -- up to 40% larger -- in toddlers with autism compared to neurotypical counterparts, UC San Diego Today reported.

Lead researcher Eric Courchesne, Co-Director of UC San Diego's Autism Center of Excellence, highlighted the study's findings, saying, "We found the larger the embryonic BCO size, the more severe the child's later autism social symptoms."

"Toddlers who had profound autism, which is the most severe type of autism, had the largest BCO overgrowth during embryonic development. Those with mild autism social symptoms had only mild overgrowth."

Published in Molecular Autism, the study revealed a parallel between the size of BCOs and abnormalities in social brain regions, underscoring diminished social attention in severe cases of autism. Alysson Muotri, Ph.D., co-researcher and director at the Sanford Stem Cell Institute, emphasized, "The bigger the brain, the better isn't necessarily true."

Mirian A.F. Hayashi, Ph.D., a collaborator from the Federal University of São Paulo, identified a potential molecular culprit: the protein NDEL1, essential for regulating embryonic brain growth, was found to be deficient in BCOs of autistic toddlers, correlating with their excessive enlargement.

Courchesne stressed the urgency of understanding these early developmental differences, saying, "That understanding can only come from studies like ours, which reveals the underlying neurobiological causes of their social challenges and when they begin."

Looking ahead, the researchers aim to uncover additional molecular factors contributing to brain overgrowth in autism. These discoveries hold promise for developing targeted therapies to enhance social and cognitive functioning in individuals affected by the condition.