Autism spectrum disorder (ASD) is thought to occur roughly four times as frequently in boys as it does in girls, and a new study in the journal Brain may have finally hit upon the reason for this disparity. After analyzing the genetic changes underlying the condition, the researchers found evidence for a “female protective effect”, whereby a significantly greater number of genetic mutations is required for the appearance of autism-like 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 enhances our understanding of the condition and suggests that any conclusions drawn from previous studies into autism in boys may not hold true for girls.
"We know so little about how autism unfolds in the brain," explained study author Dr Abha Gupta in a statement. "It's important to be able to land on spots where the dysfunction might arise because that gives us more traction into where in the brain to look. We need to be accurate about this."
Given the comparatively high rates of autism diagnoses in boys, it is perhaps unsurprising that the majority of prior research into the condition has been conducted on boys. As a consequence, ASD in girls has remained under-explored, making it difficult for scientists to determine why autism is so much less common in girls.
To solve this riddle, 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 pat-a-cake, before comparing these to scans taken from 45 girls and 47 boys without autism.
Results confirmed several existing theories regarding the nature of autism in boys, with those with ASD displaying less activity in a brain region called the 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 pick up on social cues.
However, when analyzing the girls’ brain scans, the researchers found that ASD was predominantly driven by lower activation of a brain structure called the 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 language 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 conducted a genetic analysis of 61 girls and 65 boys with autism. They found that an average of 144,378 base pair mutations was required in order to produce ASD symptoms in girls, whereas autistic boys had an average of 106,740 mutations. In girls, the majority of these mutations were associated with genes that control the development of the striatum, thus confirming the significance of this particular brain region for autism in girls.
To confirm this finding, the study 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 the majority of these associated with the striatum.
Taken together, these results not only highlight the differences between ASD in girls and boys, but also provide some explanation for the "female protective effect", implying that considerably more genetic mutations must occur in order for girls to develop the condition.