A team of Boston and European scientists have found evidence for a “female protective effect” in autism that could explain why boys are at far greater risk for the disorder than girls.
For years, it’s been known that boys are disproportionately affected by autism spectrum disorders, outnumbering girls four to one. What has never been clear is the reason for the gender imbalance: were males more biologically suspectable, or were females somehow insulated from the disorder and its suite of communication and behavioral problems? In a study published Monday, scientists studied thousands of pairs of twins and found evidence that supports the idea that females are protected.
What remains to be done is the difficult task of pinpointing the biological reasons that underlie the gender imbalance, which could provide clues about how to prevent or treat the disorder.
“The first step is to understand what is going on. The question is whether being a girl actually truly prevents one from manifesting symptoms of autism,” said Elise Robinson, an instructor in analytic and translational genetics at Massachusetts General Hospital and Harvard Medical School who led the study, published in the Proceedings of the National Academy of Sciences.
Researchers used two large databases of thousands of fraternal twins that included information about autistic behaviors, including problems with social interactions, communication, and repetitive behaviors. Since the siblings share similar genetic risk factors and environmental exposures, studying the autistic traits the children in each family had was one way of trying to isolate the role gender could play in the disorder.
What the researchers found was a clear signal that girls were protected; in other words, females needed to have a greater burden of familial risk factors in order to manifest classical autistic behaviors. The researchers figured that out by comparing the siblings of two groups: girls whose behaviors put them in the top 10th percentile of autistic behaviors and boys who were similarly ranked. If gender had a protective effect, the researchers would expect girls to be more likely to have a sibling with autistic traits than boys in the same group. That's because girls would need more familial risk factors to overcome the protective effect, and those same risk factors would also be experienced by their siblings.
John Gabrieli, a neuroscientist at the McGovern Institute for Brain Research at the Massachusettts Institute of Technology, said that the study was striking because it shows evidence that something biological—in the genes or environment—is “muting” autistic traits in girls.
“It’s worth studying, practically, because it is so impressive. Because if you understood some of these mechanisms, maybe it would be a suggestion of a treatment for boys or prevention for boys, or a naturally-occurring preventive treatment,” Gabrieli said.
The big follow-up question is what factors could be protecting females from autism. That will be trickier to discern. Robinson said that she hopes to first take the suite of genetic risk factors that are beginning to emerge, each underlying a tiny fraction of autism risk, and go back to examine them in large populations, to see if known genetic risk factors cause greater risk to boys than girls.
She also said that it’s possible that autism in females may encompass different traits.
“The other option is being a girl changes the way a lot of these behaviors are manifested, so girls who are at risk may be protected from showing these traits that are extremely typical of autism as it is currently defined,” Robinson said. “But they might show different behaviors or have different types of behavior problems we don’t understand yet, and I think it’s important to tease things apart.”