Elise Robinson led the study.
Elise Robinson led the study.o Massachusetts General Hospital

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 4 to 1. What has never been clear is the reason for the gender imbalance: Were males more biologically susceptible, or were females somehow insulated from the disorder and its suite of communication and behavioral problems? In a paper published last Monday, scientists studied thousands of pairs of twins and found evidence that supports the idea that females are protected.


“The first step is to understand what is going on,” 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. The biological underpinnings of the gender imbalance are “interesting and important to pursue because it could kind of speak to the etiology of the disorder — what’s causing the disease.”

Researchers used two large databases of thousands of fraternal twins that included information about autistic traits, 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.

The researchers found 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 classic autistic behaviors. The researchers figured that out by comparing the siblings of two groups: girls who had the most 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. That’s indeed what the researchers found.


John Gabrieli, a neuroscientist at the McGovern Institute for Brain Research at the Massachusetts Institute of Technology, said 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, Robinson said, will be trickier to discern.

Carolyn Y. Johnson can be reached at cjohnson@globe.com. Follow her on Twitter @carolynyjohnson.