The biological origins of these opposite autism spectrum disorder social severity subtypes and developmental trajectories are not known.
In a new study in the Molecular Autism journal (Springer Link), “Embryonic origin of two ASD subtypes of social symptom severity: the larger the brain cortical organoid size, the more severe the social symptoms,” shows that brain overgrowth in embryonic brains may dictate autism severity. The conclusion is that, by embryogenesis, the biological bases of two subtypes of autism spectrum disorder (ASD) social and brain development, and specifically profound and mild autism, are already present and measurable, and involve dysregulated cell proliferation, as well as accelerated neurogenesis and growth. The larger the embryonic BCO size in ASD, the more severe the future social symptoms, and the more reduced the social attention, language ability, and IQ, as well as the more atypical the growth of social and language brain regions.
The Abstract Results follows.
Abstract (Results)
At the BCO level, analyses showed BCO size was significantly enlarged by 39% and 41% in ASD in the 2021 and 2022 batches. The larger the embryonic BCO size, the more severe the ASD social symptoms. Correlations between BCO size and social symptoms were r = 0.719 in the 2021 batch and r = 0. 873 in the replication 2022 batch. ASD BCOs grew at an accelerated rate nearly 3 times faster than controls. At the cell level, the two largest ASD BCOs had accelerated neurogenesis. At the molecular level, Ndel1 activity was highly correlated with the growth rate and size of BCOs. Two BCO subtypes were found in ASD toddlers: Those in one subtype had very enlarged BCO size with accelerated rate of growth and neurogenesis; a profound autism clinical phenotype displaying severe social symptoms, reduced social attention, reduced cognitive, very low language and social IQ; and substantially altered growth in specific cortical social, language and sensory regions. Those in a second subtype had milder BCO enlargement and milder social, attention, cognitive, language and cortical differences.
