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Excess brain growth in the womb is linked to autism severity
Last reviewed: 02.07.2025
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Some children with autism experience profound, lifelong difficulties, such as developmental delays, social problems, and even the inability to speak. Others have milder symptoms that improve over time.
This difference in outcomes has long puzzled scientists, but now a new study published in the journal Molecular Autism by researchers at the University of California, San Diego, sheds light on the matter. Among its findings: the biological basis for these two subtypes of autism develops in the womb.
The researchers used stem cells taken from the blood of 10 toddlers aged 1 to 4 years with idiopathic autism (for which no single-gene cause has been identified) to create brain cortical organoids (BCOs) – models of the fetal cerebral cortex. They also created BCOs from six neurotypical toddlers.
The cerebral cortex, often called gray matter, lines the outer surface of the brain. It contains tens of billions of nerve cells and is responsible for important functions such as consciousness, thinking, reasoning, learning, memory, emotion, and sensory functions.
Among their findings, the researchers found that the BCOs of children with autism were significantly larger — by about 40% — than those of neurotypical controls. This was confirmed by two rounds of studies conducted in different years (2021 and 2022). Each round involved the creation of hundreds of organoids from each patient.
The researchers also found that the abnormal growth of the BCO in toddlers with autism correlated with the manifestation of their disorder. The larger the size of a toddler’s BCO, the more severe their social and language symptoms later in life, and the larger their brain structure was on MRI. Toddlers with abnormally large BCOs showed larger-than-normal volumes in social, language, and sensory areas of the brain compared with their neurotypical peers.
"Bigger is not always better when it comes to the brain," said Dr. Alisson Mutrey, director of the Sanford Stem Cell Institute (SSCI) at the university. "We found that brain organoids from children with profound autism have more cells and sometimes more neurons, and that's not always a good thing."
In addition, the BCOs of all children with autism, regardless of severity, grew about three times faster than those of neurotypical children. Some of the largest brain organoids—those with the most severe, persistent cases of autism—also showed accelerated neuron production. The more severe a child’s autism, the faster their BCOs grew—sometimes to the point of developing an excess number of neurons.
Eric Courchesne, a professor in the School of Medicine's department of neurology and co-leader of the study with Mutry, called the research "unique." Matching data on children with autism — including their IQ, symptom severity, and MRI results — with their corresponding BCOs or similar stem-cell models is powerful, he noted. But surprisingly, such studies had not been done before their work.
"The core symptoms of autism are social-emotional and communication problems," said Courchesne, who is also co-director of the UC San Diego Center of Excellence in Autism. "We need to understand the underlying neurobiological causes of these problems and when they start to develop. We are the first to develop stem cell research in autism that addresses this specific and central question."