Pregnant woman with fetus

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SAN DIEGO — Having a bigger brain is something most people would immediately say is a good thing. However, a new study finds that when the brain grows too fast, it can actually signal the onset of autism. Moreover, researchers in California have found that doctors can spot overgrown brains before a child is even born.

The findings, in a nutshell:

Autism spectrum disorder (ASD) is a complex condition that affects children in vastly different ways. Some kids experience mild symptoms that improve over time, while others face severe, lifelong challenges such as the inability to speak. This disparity has long puzzled scientists, but researchers from the University of California-San Diego reveal that the biological basis for these two subtypes of autism — mild and profound — develops before birth, in the womb.

The key lies in the brain’s cortex, often referred to as gray matter. This outer layer of the brain is responsible for essential functions like consciousness, thinking, learning, memory, and emotions. Using a unique method, researchers found that in toddlers with autism, the cortical region is about 40% larger than in neurotypical children. Moreover, the abnormal size of this region correlates with symptom severity: the larger a toddler’s cortical area, the more severe their social and language difficulties later in life.

The bigger the brain, the better isn’t necessarily true,” explains Alysson Muotri, Ph.D., director of the Sanford Stem Cell Institute (SSCI) Integrated Space Stem Cell Orbital Research Center at UC San Diego, in a media release. “We found that in the brain organoids from toddlers with profound autism, there are more cells and sometimes more neurons — and that’s not always for the best.”

brain organoids in lab
Brain cortical organoids (BCOs) created by Dr. Alysson Muotri shown in a 2019 file photo. Muotri and colleagues at the University of California San Diego used stem cells from toddlers with autism and created BCOs from them. The stem cells of toddlers with autism developed into larger BCOs, they discovered. Toddlers with autism also had larger brain volumes, according to MRI. (CREDIT: UC San Diego Health Sciences)

How did researchers make this discovery?

To uncover these insights, published in the journal Molecular Autism, researchers took blood samples from 10 toddlers between the ages of one and four with idiopathic autism (where no single-gene cause is identified) and six neurologically normal toddlers. From these blood samples, they extracted stem cells — versatile cells that can turn into various cell types. Using these stem cells, they created brain cortical organoids (BCOs), which are essentially miniature models of the fetal cortex.

Think of BCOs as tiny, simplified versions of a developing brain. Just as a model airplane helps engineers understand a real plane’s aerodynamics, these BCOs help scientists understand how a real fetal brain develops. The team created hundreds of these mini-brains (organoids) from each child’s stem cells, allowing them to study brain development in a way that would be impossible with actual fetal brains.

In two separate studies in 2021 and 2022, the researchers observed something striking: the BCOs from toddlers with autism were about 40% larger than those from neurotypical children. This wasn’t just a size difference — it also correlated with real-life symptoms. Children whose BCOs were larger had more severe social and language difficulties later in life. When these children had brain scans (MRIs), the images showed greater-than-typical volume in areas associated with social interaction, language, and sensory processing.

However, study authors say size wasn’t the only difference. The BCOs from children with autism grew about three times faster than those from neurotypical kids. In some cases, particularly in children with the most severe forms of autism, this rapid growth led to an excess of neurons. It’s a bit like a garden where plants are growing too quickly and densely — while it might seem like more growth is better, it can actually make the garden less functional and harder to maintain.

The researchers also delved into the molecular level, examining a protein called Ndel1. This protein is known to regulate cell growth and division. They found that Ndel1’s activity was closely linked to how fast and large the BCOs grew, suggesting it plays a key role in the overgrowth seen in autism.

This research is groundbreaking because it’s the first to match data from real children — including IQ scores, symptom severity, and brain scans — with their corresponding BCOs. By doing so, the team has shown that the roots of autism’s varying severity lie in prenatal brain development, opening new avenues for early diagnosis and potentially, future therapies.

This work was supported by grants from the National Institute of Deafness and Communication Disorders, the National Institutes of Health, the California Institute for Regenerative Medicine, and the Hartwell Foundation.

About Chris Melore

Chris Melore has been a writer, researcher, editor, and producer in the New York-area since 2006. He won a local Emmy award for his work in sports television in 2011.

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