A Yale University study found that autism is associated with two types of neurodevelopmental abnormalities that occur early in brain development, and that these differences depend on brain size. Using brain organoids derived from stem cells of autistic children, researchers discovered distinct neuronal growth patterns that could potentially guide personalized treatments and diagnostics.

Early brain development and autism

Two distinct neurodevelopmental abnormalities that occur weeks after the brain begins to develop are linked to the onset of autism spectrum disorders, according to Yale University research in which scientists grew brain organoids from stem cells of boys diagnosed with autism.

The researchers say the specific abnormalities are determined by the size of the child’s brain, and that the discovery could help doctors and researchers diagnose and treat autism in the future. The results of the study were published in the journal Nature Neuroscience.

Insights from brain organoids

“It’s surprising that children with the same symptoms show two very differently altered neural networks,” says Dr. Flora Vaccarino, Harris Professor at the Children’s Research Center at Yale School of Medicine and a co-author of the paper.

Using stem cells collected from 13 boys diagnosed with autism (including one with macrocephaly, a condition that results from an enlarged head), the Yale team created brain organoids—small, three-dimensional replicas of the developing brain—in a lab dish to simulate the growth of neurons in a fetus. They then compared the brain development of these boys to their parents. (The patients were recruited from other clinicians at the Yale Child Study Center, which conducts research, service, and education to advance understanding of the health issues facing children and their families.)

The study was co-led by Alexandre Jourdon, Feinan Wu, and Jessica Mariani of the Vaccarino Laboratory at Yale School of Medicine.

Autism and brain growth

Approximately 20% of autism cases occur in people with macrocephaly, a condition in which a child’s head size is 90% or greater at birth. This is usually a more serious condition among autism cases.

Interestingly, the researchers found that children with autism and macrocephaly had an overgrowth of excitatory neurons compared to their parents, while organoids from other children with autism showed a lack of the same types of neurons.

Importance of diagnosis and treatment

The ability to track the growth of specific types of neurons could help doctors diagnose autism, whose symptoms typically appear 18 to 24 months after birth, the study authors said.

The research findings could also help identify cases of autism who might benefit from existing drugs designed to relieve symptoms of disorders characterized by excessive excitatory activity of neurons, such as epilepsy, Vaccarino said. People with macrocephaly may benefit from such drugs, but patients whose brains are not large may not, he said.

Establishing biobanks of patient-derived stem cells may be important for tailoring treatments to specific individuals or for personalized medicine.