Rapid prenatal brain growth linked to Autism Spectrum Disorder

Friday, July 12, 2024.

Autism spectrum disorder (ASD) encompasses a wide range of symptoms and challenges that affect children differently.

While some children exhibit mild symptoms that improve over time, others face severe, lifelong difficulties, such as nonverbal communication.

Scientists have long been puzzled by this variability.

However, a groundbreaking 2024 study from the University of California-San Diego suggests that the biological roots of these different autism subtypes — mild and severe — begin in the womb.

The role of brain growth in autism

The research team found that the brain’s cortex, particularly the gray matter, plays a critical role in this early development.

The cortex is crucial for functions like consciousness, thinking, learning, memory, and emotions. Using a novel approach, researchers discovered that toddlers with autism had a cortical region about 40% larger than that of neurotypical children.

Furthermore, the extent of this enlargement correlated with the severity of their symptoms: the larger the cortex, the more significant the social and language challenges observed later in life.

Not Always "Bigger is Better"

Dr. Alysson Muotri, director of the Sanford Stem Cell Institute (SSCI) Integrated Space Stem Cell Orbital Research Center at UC San Diego, emphasized that a larger brain is not always advantageous. “We found that in brain organoids from toddlers with profound autism, there are more cells and sometimes more neurons — and that’s not always beneficial,” he explained.

How The Study Was Conducted

To arrive at these findings, published in Molecular Autism, the researchers used blood samples from 10 toddlers aged one to four with idiopathic autism (where no single-gene cause is identified) and six neurotypical toddlers.

From these samples, they extracted stem cells, which can develop into various cell types.

These stem cells were used to create brain cortical organoids (BCOs), miniature models of the fetal cortex.

BCOs serve as simplified versions of a developing brain, similar to how a model airplane helps engineers understand a real airplane’s aerodynamics. The researchers could study brain development in unprecedented detail by creating hundreds of these mini-brains from each child’s stem cells.

Key Findings:

The studies conducted in 2021 and 2022 revealed that BCOs from autistic toddlers were about 40% larger than those from neurotypical children.

This size difference was directly linked to the severity of symptoms. MRI scans of these children showed that those with larger BCOs had more significant social and language impairments.

Additionally, these BCOs grew approximately three times faster than those from neurotypical children, leading to an excess of neurons in severe cases of autism. This overgrowth can be likened to a garden with plants growing too rapidly and densely, making it less functional.

On a molecular level, the researchers examined the protein Ndel1, which regulates cell growth and division. They discovered that Ndel1 activity was closely associated with the rapid and large growth of BCOs, indicating its significant role in the overgrowth observed in autism.

Implications for Early Diagnosis and Therapy

This research is pioneering because it aligns data from actual children — including IQ scores, symptom severity, and brain scans — with their corresponding BCOs.

The findings suggest that the varying severity of autism has its origins in prenatal brain development, offering new pathways for early diagnosis and potential future treatments. This is extremely promising research.

Be Well, Stay Kind, and Godspeed.

REFERENCES:

Courchesne, E., Taluja, V., Nazari, S. et al. Embryonic origin of two ASD subtypes of social symptom severity: the larger the brain cortical organoid size, the more severe the social symptoms. Molecular Autism 15, 22 (2024). https://doi.org/10.1186/s13229-024-00602-8