The extent of Autism Spectrum Disorder (ASD) varies across children. Certain children diagnosed with ASD, also known as autism, may face significant challenges throughout their lives, such as delays in development, difficulties in social interactions, and possible speech impairments. On the other hand, there are those who exhibit milder symptoms that show signs of improvement over time (1^✔ ✔Trusted Source
Embryonic origin of two ASD subtypes of social symptom severity: the larger the brain cortical organoid size, the more severe the social symptoms

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The discrepancy in outcome has remained a puzzle for the scientists, but a recent investigation conducted by experts at the University of California San Diego has finally provided some insight. This groundbreaking study has been published in Molecular Autism; it unveils crucial information on this disorder, for the first time. Remarkably, the research reveals that the biological foundation for these two distinct autism subtypes originates during prenatal development.

Scientists utilized blood-derived stem cells from 10 young children, ranging from 1 to 4 years old, diagnosed with idiopathic autism (a condition in which no single-gene cause was identified) to create brain cortical organoids (BCOs), which are representations of the fetal cortex. In addition, BCOs were generated from six typically developing toddlers.

The cortex, commonly known as gray matter, surrounds the brain’s exterior. It contains billions of nerve cells and plays a crucial role in functions such as consciousness, cognition, logic, memory, emotions, and sensory processing.

In their research, it was discovered that the brain cortical organoids (BCOs) of toddlers with autism were notably larger, approximately 40 percent, compared to the BCOs of neurotypical controls. This finding was consistent across two separate studies conducted in different years, specifically 2021 and 2022. Each study involved the generation of numerous organoids from every patient involved in the research.

The study conducted by researchers revealed a connection between abnormal BCO growth in toddlers with autism and the severity of their disease symptoms. Children with larger BCO size exhibited more severe social and language symptoms in their later years, as well as larger brain structures on MRI scans. Young children with excessively enlarged BCOs exhibited above-average volume in areas of the brain related to social interaction, language, and sensory processing when compared to their neurotypical counterparts.

“The bigger the brain, the better isn’t necessarily true,” said Alysson Muotri, Ph.D., director of the Sanford Stem Cell Institute (SSCI) Integrated Space Stem Cell Orbital Research Center at the university. The SSCI is directed by Catriona Jamieson, M.D., Ph.D., a leading physician-scientist in cancer stem cell biology whose research explores the fundamental question of how space alters cancer progression.

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Muotri, who is also a professor in the Departments of Pediatrics and Cellular and Molecular Medicine at the UC San Diego School of Medicine added, “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,”

Furthermore, the BCOs of all children with autism, irrespective of the severity, exhibited a growth rate approximately three times higher than that of neurotypical children. Notably, the largest brain organoids derived from children with the most severe and persistent cases of autism displayed an accelerated formation of neurons. In fact, the BCOs of toddlers with more severe autism grew at an even faster pace, occasionally resulting in an excessive number of neurons.

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Dr. Eric Courchesne, a professor in the Department of Neurosciences at the School of Medicine, who worked alongside Muotri on this research, characterized the study as unparalleled. He stressed the importance of aligning information on children with autism, such as their IQs, symptom severity, and imaging data from MRIs, with their corresponding BCOs or similar stem cell-derived models. He stated that this methodology is highly logical. Surprisingly, no research of this kind had been carried out before their study.

Courchesne, who also serves as co-director of the UC San Diego Autism Center of Excellence stated, “The core symptoms of autism are social affective and communication problems,”. Courchesne further added, “We need to understand the underlying neurobiological causes of those challenges and when they begin. We are the first to design an autism stem cell study of this specific and central question.”

It has long been believed that autism, a collection of intricate progressive disorders, initiates during the prenatal period and encompasses various stages and mechanisms. These include disruptions in the embryonic processes that control cell proliferation, neurogenesis, and growth. Individuals with autism are unique, just like neurotypical individuals, and can typically be classified into two main groups: those facing significant social challenges needing lifelong support, possibly being nonverbal, and those with a less severe form of the condition who eventually acquire strong language abilities and social connections.

With this assessment, Courchesne and Muotri have now confirmed that brain overgrowth initiates during fetal development. Their goal is to identify the root cause of this phenomenon in order to create a treatment that could potentially improve cognitive and social abilities in individuals affected by the condition.

Reference:

1. Embryonic origin of two ASD subtypes of social symptom severity: the larger the brain cortical organoid size, the more severe the social symptoms
   – (https://molecularautism.biomedcentral.com/articles/10.1186/s13229-024-00602-8)

Source-Medindia