Researchers have found a correlation between the size of embryonic brain cortical organoids and the severity of social symptoms in toddlers with autism spectrum disorder.
A recent study identified biological markers distinguishing two subtypes of autism spectrum disorder (ASD) based on social symptom severity. This research, published in Molecular Autism, utilized embryonic brain cortical organoids (BCOs) to investigate the correlation between BCO size and ASD symptoms in toddlers.
The study measured BCO size and growth in 4,910 organoids derived from 10 toddlers with ASD and 6 controls. The BCOs from ASD toddlers were larger than those from controls, with a 39-41% increase in size. The correlation between BCO size and social symptom severity in ASD toddlers was in the 2021 batch was 0.719 and in the 2022 batch was 0.873.
Two distinct ASD subtypes were identified. The first subtype, associated with profound autism, was characterized by very large BCOs and rapid growth rates. Toddlers in this group had more pronounced social symptoms, reduced social attention, and lower cognitive and language skills. The second subtype showed milder BCO enlargement and correspondingly milder symptoms.
At the cellular level, ASD BCOs demonstrated accelerated neurogenesis, particularly in the largest organoids. Molecular analyses revealed that the activity of NDEL1, a gene involved in cell proliferation and neurogenesis, was correlated with BCO growth rate and size. Lower NDEL1 activity was linked to larger BCOs and more severe social symptoms.
These findings indicated that the biological underpinnings of ASD social symptom severity are established during embryogenesis.
Full disclosures can be found in the original study.