A new study has found that highly severe genetic mutations linked to autism may overpower the biological mechanisms that are believed to protect females from developing the disorder.
Autism spectrum disorder is diagnosed more often in males than females, leading scientists to believe that females may have natural protective factors that reduce their vulnerability. However, researchers from the Korea Advanced Institute of Science and Technology (KAIST), Yonsei University, and the Institute for Basic Science said strong experimental proof for this theory has been limited.
The study focused on the gene CHD8, one of the major genetic risk factors associated with autism and other neurodevelopmental disorders. This gene plays a crucial role in regulating brain development.
Researchers created what they described as the world’s first viable mouse model carrying severe CHD8 mutations inherited from both parents. This allowed them to examine how mild and severe mutations affect brain development, behaviour, neural activity and gene expression.
The findings showed that mice with a single mutated CHD8 gene displayed autism-like behavioural changes mainly in males, matching the higher prevalence of autism seen in human males.
However, mice with severe mutations in both copies of the gene developed significant autism-related abnormalities regardless of sex. These mice also showed enlarged brain size, abnormal blood flow in the brain, disrupted brain activity patterns, and other neurological changes linked to autism.
According to the researchers, the differences between males and females became less noticeable as the severity of the mutation increased. This suggests that female protective mechanisms may work only up to a certain level of genetic disruption.
“Our findings suggest that females may possess protective biological mechanisms against CHD8-related dysfunction, but severe mutations can overwhelm those protective effects,” said Eunee Lee, professor at Yonsei University.