Study Associates Two Neurodevelopmental Abnormalities with Autism Emergence

Two distinct neurodevelopmental abnormalities that arise just weeks after the start of brain development have been associated with the emergence of autism spectrum disorder, according to a new Yale-led study in which researchers developed brain organoids from the stem cells of boys diagnosed with the disorder.

And, the team reports in a paper published in Nature Neuroscience, that the specific abnormalities seem to be dictated by the size of the child’s brain, a finding that could help doctors and researchers to diagnosis and treat autism in the future.

“It’s amazing that children with the same symptoms end up with two distinct forms of altered neural networks,” said Flora Vaccarino, co-senior author of the paper.

Using stem cells collected from 13 boys diagnosed with autism—including eight boys with macrocephaly—the team created brain organoids in a lab dish that mimic neuronal growth in the fetus. They then compared brain development of these affected children with their fathers. About 20% of autism cases involve individuals with macrocephaly. Among autism cases these tend to be more severe.

Intriguingly, the researchers found that children with autism and macrocephaly exhibited excessive growth of excitatory neurons compared with their fathers while organoids of other children with autism showed a deficit of the same type of neurons.

The ability to track the growth of specific types of neurons could help doctors diagnose autism, symptoms of which generally appear 18 to 24 months after birth, the authors say.

The findings may also help identify autism cases that might benefit from existing drugs designed to ameliorate symptoms of disorders marked by excessive excitatory neuron activity, such as epilepsy, Vaccarino said. Autism patients with macrocephaly might benefit from such drugs while those without enlarged brains may not, she said.