Female Sex May Protect Against Autism

Megan Brooks

February 20, 2013

Autistic behaviors may be less common in girls because girls are less susceptible to some of the genetic and environmental factors that increase risk for autistic spectrum disorders (ASDs), new research suggests.

Dr. Elise Robinson

"There is a well-established sex bias in ASDs — specifically, the overall male to female ratio is about 4:1," Elise Robinson, ScD, of the Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, told Medscape Medical News.

"We were interested in better understanding that pattern through the lens of a potential female protective effect. In other words — are females affected less frequently because they are less susceptible to some of the genetic and environmental factors that create risk for ASDs? That is the primary implication of the study, and it will need to be replicated in future efforts," Dr. Robinson said.

The study was published online February 19 in Proceedings of the National Academy of Sciences.

Investigators examined data from 2 large, independent cohorts of fraternal twins: 3842 12-year-old twin pairs in the UK-based Twin's Early Development Study, and 6040 9- to 12-year-old twin pairs in the Swedish Child and Adolescent Twin Study.

In both groups, they compared sibling autistic traits between female and male probands, who were identified as scoring in the top 90th and 95th percentiles of the population autistic trait distributions.

In both study groups, siblings of female probands displayed significantly greater average impairments than the siblings of male probands. This suggests that girls may require greater "etiologic load" to manifest autistic behavior, the authors note.

Reached for comment, Richard E. D'Alli, MD, chief of the Division of Child Development and Behavioral Health from Duke Medicine in Durham, North Carolina, who was not involved in the study, cautioned that there really "isn't anything new here," and he does not think it "moves the science forward."

"If you really believed that the female organism was different in some way to the male organism, that would explain why 5 times as many boys are afflicted with autism. Then you'd be looking for something that has something to do with the development of the disease," he told Medscape Medical News.

"For example, if there are certain circuits in the brain that we know or certain biochemical events that occur during development that predisposes a kid to autism, you'd ask, 'Is there a kind of difference in either the neurohormonal makeup of the female brain compared with the male brain that makes the male brain more sensitive to development of these aberrant circuits?' You would be looking for a neurochemical, or a neurohormonal, or a neuroelectrical circuity difference," Dr. D'Alli said.

Dr. Robinson said her team pursued the study "primarily for its research implications."

"A female protective effect, which we found evidence for, would suggest that a greater average concentration of risk factors may be associated with ASDs in girls as compared to ASDs in boys. If our findings are replicated, this knowledge could help us pursue genetic and environmental studies of ASDs more efficiently, and better interpret our findings," she said.

The authors and Dr. D'Alli have disclosed no relevant financial relationships.

Proc Natl Acad Sci. Published online February 19, 2013. Abstract