Khaberni - Autism spectrum disorder reveals a clear gap in diagnosis rates between genders, where males are diagnosed at about four times the rate of females, a phenomenon that has long puzzled researchers and raised questions about its true causes.
For years, this disparity has been attributed to bias in diagnostic tools and scientific studies that primarily focused on males, leading to the entrenchment of a "male" stereotype of autism. As a result, the cases of girls and women are often overlooked, misdiagnosed, or diagnosed in later stages, which in turn has reflected on the limited representation of females in scientific research, leaving the scientific understanding of autism in females incomplete.
However, recent studies have started to lean towards a biological explanation for this disparity. Here a theory known as "female protective effect" emerges, which suggests that females have a biological protection that reduces the likelihood of autism symptoms compared to males. This hypothesis is based on observations that females with autism require a greater genetic burden—such as a higher number of mutations—to exhibit symptoms.
In this context, recent research conducted by David Page’s laboratory at the Whitehead Institute offers a potential genetic explanation for this effect. The research indicates that biological differences between the genders, specifically related to the X chromosome, may play a significant role in this bias.
This work is part of broader efforts to understand the biological bases for differences between the genders in disease, extending to areas such as heart disease, autoimmune disorders, and certain types of cancer. Page asserts that the existence of differences between the genders in multiple diseases supports the idea that the disparity in autism is not due solely to social or diagnostic factors.
Researchers focus on the role of the X chromosome, as females possess two copies of it (XX), compared to one copy in males (XY). Contrary to previous beliefs that the second X chromosome is inactive, recent studies have shown that it plays a crucial role in regulating gene activity, including genes linked to autism.
The research also highlights a group of genes that "escape" inactivation on the X chromosome and continue to operate from both copies in females. These genes are sensitive regulators affecting the activity of thousands of other genes within cells. Thanks to having an additional copy of these genes, females may better mitigate the impact of mutations associated with autism compared to males.
This protective effect is not limited to autism alone, but may also extend to include a number of other congenital and developmental disorders that affect males at higher rates. Researchers believe that understanding these biological mechanisms could pave the way for improving diagnostic methods and developing more accurate and equitable treatment strategies between the genders.
