Last Updated on May 20, 2026 by Staff
Autism spectrum disorder affects boys more often than girls. In fact boys are diagnosed with autism about four times more often than girls. For a time scientists have thought that girls might have some kind of natural protection that helps prevent them from getting autism. Scientists have had a hard time figuring out how this protection works.
Now a big new study from scientists in South Korea has found some evidence that the severity of genetic mutations might be the key to understanding this protection. The study was done by experts from KAIST, Yonsei University and the Institute for Basic Science and the results were published in the journal Molecular Psychiatry.
The team looked at a gene called CHD8 which’s one of the strongest known genetic risk factors for autism and other neurodevelopmental disorders. This study might help explain why autism symptoms and sex differences vary much from person to person.
The CHD8 Gene
The CHD8 gene plays a role in brain development. It controls how other genes turn on and off during the formation of the system. Because of this even small disruptions in CHD8 can have an impact on brain growth and function.
Previous studies on animals mainly looked at mice with one damaged copy of the CHD8 gene. These mice had mild autism-like symptoms, which made it hard for scientists to study more severe forms of autism.
Scientists had tried to create mice with mutations in both copies of CHD8. Those experiments failed because the embryos could not survive during development.
To solve this problem the Korean team used a special genetic background that allowed the mice to survive even with severe CHD8 mutations. This was the time scientists were able to create viable mice with severe CHD8 mutations.
This breakthrough allowed scientists to compare severe mutations directly and see how they affected brain development and behavior in both males and females.
Male-Female Shift
The study found a difference between mild and severe genetic mutations.
Mice with one defective CHD8 gene mainly showed autism-like behaviors in males, which is similar to what we see in humans. Female mice with the mild mutation had far fewer symptoms, which supports the idea that females have some kind of natural protection.
When both copies of the CHD8 gene were mutated the picture changed completely.
In these affected mice autism-related abnormalities appeared strongly in both males and females. The female protection was much weaker which suggests that severe genetic disruptions can overwhelm the brain’s natural defense mechanisms.
Scientists also noticed that many behavioral and biological differences between female mice disappeared as the mutation severity increased. This finding suggests that sex differences in autism might not be fixed. Instead it depends on how strongly the brain’s genetic systems are disrupted.
According to Professor Lee Eunee of Yonsei University the results show that females may have biological mechanisms but powerful mutations can break through those protections.
Brain changes
The mice with CHD8 mutations had several major brain abnormalities linked to autism and other developmental disorders.
Researchers saw brain volume changes in blood flow disrupted brain rhythms and widespread changes in gene activity. Many of the genes were connected to synaptic signaling, RNA processing and mitochondrial function which are all important for healthy brain communication and energy production.
These biological changes are commonly associated with autism, ADHD, intellectual disability and schizophrenia.
By studying both the behavior and brain activity of the mice researchers got an understanding of how severe CHD8 mutations alter neural circuits during development.
The study also showed that autism severity can vary depending on the intensity of disruption. This might explain why some people have symptoms while others face more serious developmental challenges.
Future Impact
The findings could have implications for future autism research and treatment development.
Scientists think the study provides a foundation for creating personalized therapies that consider both biological sex and the severity of genetic mutations. Of treating autism as a single condition future approaches might focus on the specific genetic and neurological mechanisms involved in each individual case.
Director Kim Eunjoon of the IBS Center for Synaptic Brain Dysfunctions said the study successfully revealed mechanisms of severe autism at both genetic and brain-circuit levels.
Beyond autism the research might also help scientists better understand why many other neurodevelopmental disorders show differences between males and females.
The team hopes their new mouse model will allow researchers around the world to further investigate autism and discover more targeted therapeutic strategies in the future.