Autism Spectrum Disorder (ASD) is thought to appear about four times more often in boys than in girls, and a new study in the journal Brain may have finally hit the cause of this inequality. Analyzing the genetic changes under the condition, the researchers found evidence of a “female protective effect,” whereby a significantly larger number of genetic mutations are needed for the onset of autism symptoms in girls versus boys.
Moreover, the results suggest that the genes involved tend to relate to different brain regions between the two – meaning that the neural mechanism that drives ASD in girls is in fact distinct from that seen in boys. This finding significantly improves our understanding of the condition and suggests that some conclusions from previous studies on autism in boys may not apply to girls.
“We know so little about how autism develops in the brain,” study author Dr. Abha Gupta explained in a statement. “It’s important to be able to land on places where the malfunction might arise, because that gives us more traction in the appearance of the brain. We need to be accurate about that.”
Given the relatively high rates of autism diagnoses in boys, it is perhaps surprising that the majority of previous research on the condition has been done in boys. As a consequence, ASD in girls has remained underestimated, making it difficult for scientists to determine why autism is so less common in girls.
To solve this puzzle, the study authors scanned the brains of 45 girls and 47 boys with autism as they observed displays of people performing “child-friendly movements” such as waving or playing cookie, before comparing these with scans taken by 45 girls and 47 boys without autism.
Results confirmed several existing theories about the nature of autism in boys, with those with ASD showing less activity in a brain region called a posterior superior temporal sulcus than those without the condition. Generally involved in the processing of auditory and visual stimuli, this key brain region is also thought to play a role in our ability to recognize social signals.
However, when analyzing girls ’brain research, the researchers found that ASD is primarily driven by lower activation of a brain structure called putamen, which is located within the striatum. The putamen is mostly known for its role in motor function but is also thought to be involved in social and linguistic functions. In other words, the brain regions that contribute to the development of ASD in girls are not necessarily the same as those that underlie the condition in boys, according to this study.
The researchers also did a genetic analysis of 61 girls and 65 boys with autism. They found that an average of 144,378 basic pair mutations were needed to produce ASD symptoms in girls, while autistic boys had an average of 106,740 mutations. In girls, the majority of these mutations have been associated with genes that govern the development of the striatum, thus confirming the significance of this particular brain region for autism in girls.
To confirm this finding, the study’s authors cross-referenced their results with data from the Simons Simplex Collection, which contains genetic information from thousands of families with at least one autistic member. Here again, they found that girls with ASD tended to have a higher number of mutations than boys, with most of these associated with the streak.
Taken together, these results not only highlight the differences between ASD in girls and boys, but also give some explanation for the “female protective effect,” implying that considerably more genetic mutations must occur for girls to develop the condition.