A quarterly publication of the Autism Research Institute
Summer, 2024 | Number 3, Volume 38
Differences in brain size and growth correlate with the severity of symptoms in children with autism spectrum disorders (ASD), according to a study from researchers in the United States, China, Brazil, and Italy.
Eric Courchesne and colleagues initially used peripheral blood stem cells from ten toddlers with ASD and five neurotypical controls to develop embryonic-stage brain cortical organoids (BCOs), which are tissue collections that mimic the structure and functions of the fetal cortex. They then measured the size and growth of the organoids. Later, they replicated their findings in an independent batch of BCOs from six of the original children with ASD and four neurotypical controls, including one child who was not in the original group. Overall, they measured the size and growth of 4,910 BCOs, or an average of 196 individual BCOs per child.
The researchers report that the BCOs of the children with ASD were approximately 40% larger than those of neurotypical controls. Moreover, the BCOs of children with ASD grew at a rate nearly three times that of neurotypical controls, and the BCOs of children with the greatest overgrowth exhibited accelerated formation of new neurons. At the molecular level, there was an inverse correlation between the growth rate of ASD organoids and the activity of Ndel1, a gene involved in multiple processes in the embryonic brain.
In addition, the researchers report, “The larger the embryonic BCO size, the more severe the ASD toddler’s social symptoms; the more reduced the IQ, social attention, and language ability; and the more atypical the social, language, and sensory brain growth.”
The researchers conclude, “By embryogenesis, the biological bases of two contrasting subtypes of ASD social and brain development—profound/severe autism and mild autism—are already distinguishable and measurable and involve dysregulated proliferation and accelerated neurogenesis and growth.”
“Embryonic origin of two ASD subtypes of social symptom severity: the larger the brain cortical organoid size, the more severe the social symptoms,” Eric Courchesne, Vani Taluja, Sanaz Nazari, Caitlin M. Aamodt, Karen Pierce, Kuaikuai Duan, Sunny Stophaeros, Linda Lopez, Cynthia Carter Barnes, Jaden Troxel, Kathleen Campbell, Tianyun Wang, Kendra Hoekzema, Evan E. Eichler, Joao V. Nani, Wirla Pontes, Sandra Sanchez Sanchez, Michael V. Lombardo, Janaina S. de Souza, Mirian A. F. Hayashi, and Alysson R. Muotri, Molecular Autism, May 2024 (free online). Address: Eric Courchesne, [email protected], or Alysson R. Muotri, [email protected].
—and—
“Brain overgrowth dictates autism severity, new research suggests,” news release, University of California at San Diego, June 5, 2024.
