Brain enlargement may be linked to symptom severity in kids with autism spectrum disorder

Brain enlargement in children on the autism spectrum may be associated with some of the condition’s common symptoms. 

Specifically, social and communication symptoms appear to be more severe in children who display brain overgrowth on MRI scans. Experts believe this overgrowth may be associated with alterations in the activity of the Ndel1 enzyme, which is related to embryonic neuron differentiation and migration. 

The findings, which were published in Molecular Autism, were based on an imaging analysis of more than 900 children diagnosed with ASD and research on brain organoids, or “mini brains” grown from stem cells of the participants. The organoids mimic the structure and function of full-size brains, allowing researchers an opportunity to monitor their growth and compare it to the children’s imaging and symptoms. 

In the patients who had the most severe symptoms, brain enlargement on MRI and in the organoids were observed. In fact, the “mini brains” were up to 41% larger in children with more severe symptoms compared to a group of controls—the larger the organoid, the worse the children’s symptoms were. 

“Not all children with ASD and severe symptoms will have an enlarged brain, but the symptoms are more severe when the brain is enlarged,” Mirian Hayashi, a professor in the Department of Pharmacology at the Federal University of São Paulo’s Medical School in Brazil, said in a release on the findings. 

Ndel1 has been linked with several psychiatric and neurological conditions, such as schizophrenia and bipolar disorder, the group noted. Issues with these enzymes affect cell migration and neuron formation, which could lead to altered brain formation (in the case of the organoids) and growth (observed on imaging), the group explained. 

“These processes involve other proteins, of course, but the entire system is probably out of kilter in brain overgrowth, and Ndel1 can be a biomarker of an alteration,” João Nani, from the Department of Molecular and Cellular Medicine at the University of California, San Diego, said in the same release. “We found that this imbalance can lead to both brain enlargement and brain reduction. However, in the cases we analyzed, there were more mononuclear cells in the peripheral blood of children with autism and severity of communication and social symptoms.” 

Additional research targeting biomarkers in blood samples that could be associated with ASD severity is planned for the future.