Study Offers a Clue in Autism's Gender Divide

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A study of mutations in boys and girls with autism points to female resilience—and male susceptibility Ali Jarekji/Reuters

One of the great mysteries of autism is why many more boys are diagnosed with the disorder than girls. In the United States, 80 percent of people with autism spectrum disorder are male. It's long been known that different kinds of disorders tend to affect men and women at different rates: males are more likely to suffer from substance abuse issues, for example, and in general women are more likely to suffer from problems like depression or anxiety, as a book called The Stressed Sex has argued. But with autism, the gender disparity is particularly pronounced.

A new study, published today in the American Journal of Human Genetics, provides a clue to the mystery of gender and genetics in autism. The study involved 762 families that had been affected by autism spectrum disorder, and looked for two kinds of genetic mutations: the first is known as a copy-number variant, or CNV, and the second is called single-nucleotide variant, or SNV. Surprisingly, they discovered that the females in the study had a greater number of genetic mutations than the males. (Genetic mutations can be tied, in general, with neurodevelopmental disorders.) In a group of 653 male subjects and 109 females with autism, they found that the females had roughly two to three times as many CNVs. They discovered more SNVs in females, too.

In other words, the study suggests that it takes more mutations to lead to an autism diagnosis in females. The results paint a picture of female resilience—and male susceptibility. As the study posits, "the male brain requires milder alterations to exhibit" autism spectrum disorder, which "might be the basis for what has been described as the 'extreme male brain hypothesis,'" which has been put forward by autism researchers like Simon Baron-Cohen (incidentally, actor Sacha Baron Cohen's cousin).

Eric Butter, a pediatric neurodevelopmental psychologist and an associate professor of pediatrics at Ohio State University who works with children with autism and other disabilities, called the study "an important 'aha' moment."

Butter says the study gives "good evidence" for a genetic basis to why "boys apparently are more vulnerable to neurodevelopmental disorders and autism than girls."

While the study focuses on the number of genetic mutations in females and males, Butter says an important, and related, part of the autism-gender puzzle is how it's diagnosed, specifically in girls. "Are we asking the diagnostic questions wrong?" he wonders.

Girls tend to exhibit more severe symptoms when they have been diagnosed with the disorder. Butter wants to know if girls with more mild autistic symptoms might be being missed because of societal expectations. A girl who doesn't raise her hand in class might just be written off as shy, for example, where a boy in the same situation might get more attention, possibly leading to a diagnosis.

Robert Naseef, a clinical psychologist in Pennsylvania, has worked with autistic patients and their families for over two decades, and is also the father of a 34-year-old with autism. Naseef says that studies like this can help families by making the disorder less mysterious.

He hopes that the results will "help us look more closely at girls, and be able to identify where they're struggling." Like Butter, he says that the symptoms might be more visible, behaviorally, in boys than girls, and thus girls could be less frequently diagnosed.

The study cautions that the differences in genetic mutations can't "account completely" for the huge discrepancy between males and females diagnosed with autism, but it's a step forward. Butter adds, "This is a very important study, I think, because it is a possible explanation for the gender differences that we've found in diagnosing autism." The study doesn't answer all the questions, but Butter says that the results are "driving us towards other specific questions that other researchers can pick up."