Why Girls May Be Protected Against Autism

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Boys outnumber girls when it comes to autism diagnoses, and researchers may have uncovered one reason why.

Boys are four times more likely to be diagnosed with autism than girls, but whether that trend is rooted in biological differences between the genders or the fact that girls might simply hide their symptoms better, hasn’t been clear.

The gender-based difference could be due to factors that increase the risk among boys, or, alternatively, factors that protect girls. Researchers led by Elise Robinson of Harvard Medical School decided to investigate the latter, and determine whether there might be something about being female that protected girls from the the developmental disorder. The team analyzed data from two large samples of twins, one from Sweden and the other from the U.K.  They theorized that if something were protecting girls from autism spectrum disorders (ASDs), then families of girls who actually did develop them should have a greater than average risk, and that risk would overwhelm whatever protection they received from their gender.  In other words, girls would have a higher threshold for developing ASDs — they would have to be faced with a heavier burden of whatever genetic or environmental risk factors cause ASD in order to actually develop it.

(MORE: A Genetic Clue to Why Autism Affects Boys More)

Such family-based risk can be measured by studying levels autistic symptoms in unaffected siblings: in families at high risk of developmental and psychiatric disorders, even unaffected members tend to have mild symptoms, but not enough to qualify for a diagnosis.

“If greater familial [risk] is required to produce autistic impairments in girls, the family members of affected females should on average carry greater risk than the family members of affected males,” the authors write.  Because identical twins share the same genetics, they studied fraternal twins only, comparing sets in which only one had an autism spectrum disorder. Nearly 4,000 British twins and just over 6,000 Swedish twins were included in the research, which was published in the Proceedings of the National Academy of Sciences.

(MORE: Autism Numbers Are Rising: The Question Is Why?)

The study found that if a girl scored in the top 10% on autistic traits, the odds of her twin scoring in a similarly high range were 37% greater than those for a boy.  That meant the girls came from families with significantly greater risk levels. Because the study looked at autistic traits in a sample from the general population, rather than from those who sought treatment, the results do not simply reflect the fact that girls are less likely to be diagnosed, even if they have the condition.

“It is a really interesting and generally well-done study,” says Marjorie Solomon, associate professor of clinical psychiatry at the University of California Davis MIND Institute, who was not associated with the research. She adds, “The differences in gender ratio in ASD have been a source of great curiosity, given their many implications.”

The study was only designed to test the theory that families of girls with ASDs might have higher than risk of the disorders, and was not structured to test for exactly what it is that seems to protect girls. But that knowledge could lead to potentially better treatment options for both genders. Based on earlier research, experts see genes, rather than social or environmental factors, as the most likely explanation for lower risk among girls.

(MORE: Studies: New Clues to the Genetic Roots of Autism)

What might some of those genetic factors be? It’s possible that they may involve the social bonding hormones, oxytocin and vasopressin.  “The basic thought is that girls have less vasopressin and higher natural oxytocin,” says Solomon, “And oxytocin is a social hormone, so that would be protective.” The lower levels of vasopressin might also be helpful:  while this hormone is thought to be involved in social connections—particularly for boys, who tend to have higher levels — in animals it is also linked to aggressive defense of territory and mates.

Or it may involve other metabolic systems that aren’t as obviously connected to social development. Either way, the findings raise interesting questions about how developmental disorders like ASDs are seeded, and open up intriguing new possibilities for treating them. “An understanding of the biology underlying female advantage could greatly aid progress in understanding,” autism and “in identifying prevention factors for ASDs,” the researchers write.