‘Male brains’ linked to higher autism risk in women, study says


— Brains, like faces, have features seen as either more masculine or more feminine. One feature of brain anatomy that is characteristic of males is associated with an increased risk of autism, according to a study published Wednesday in the Journal of the American Medical Association’s Psychiatry edition.

Women with male characteristic brains are three times more likely to have autism than women with more “female” brains, the researchers say. Yet the reverse was not been proven true; no evidence indicates that men with more female-trait brains are less at risk for autism than men with typical brains.

Autism is considered a neurodevelopmental condition, which means symptoms begin early and children fail to achieve typical milestones of maturity at appropriate ages. Common symptoms include difficulty with communication and repetitive behaviors. In the United States, about one in 68 children has been identified with autism spectrum disorder, according to the Centers for Disease Control and Prevention.

The term “spectrum” refers to the fact that symptoms, levels of disability and positive skills may vary from person to person. For example, some people along the spectrum cannot make eye contact or follow simple directions, while others may be exceptional at math. And, as they age, some children with autism will learn to function more or less normally, while others will require substantial support to perform basic activities.

Autism spectrum disorder is two to five times more common in males than in females, according to Christine Ecker, lead author of the new study and a professor at Goethe University in Frankfurt, Germany. Though some researchers say sex differences in symptoms account for different rates of diagnosis, others hypothesize that sex-related variations in brain anatomy may contribute to the higher risk among males.

Gender differences

For the new study, Ecker and her co-authors examined whether brain anatomy differences led to a higher probability of autism in males. Specifically, they looked at cortical thickness: the depth of gray matter across the surface of the cortex.

“For example, it is known from previous studies that females tend to have a thicker cortex than males in various regions of the brain,” Ecker wrote in an email. Previous studies have also shown thickness to be significantly altered in people with autism.

Study participants included 98 high-functioning adults with autism (49 of them men) and 98 adults without autism (51 of them men). Both groups were roughly within the same age range: mid-20s, on average.

The researchers excluded anyone with a history of psychiatric disorders, head injuries, certain genetic disorders or other medical conditions affecting brain function, such as epilepsy. People taking mood stabilizers and other medications were also excluded.

The researchers conducted MRI brain scans on each participant and then derived cortical thickness patterns for each using a software program. After anonymizing this information, Ecker and her colleagues made predictions about which participants were male or female based on cortical thickness and overall physical characteristics, also referred to as the “brain phenotype.”

“We found that brain phenotype ranged from being typically female to typically male, and that there is variability between these extremes,” Ecker said.

This is true of all of us: Regardless of sex, our brains fall somewhere along a continuum, with extreme male and extreme female at either end. The variety in the middle is healthy and normal, said Ecker.

Among the study participants, 68.1% of the biological female brains fell closer to the female extreme while 74.5% of biological male brains fell closer to the male extreme.

Hope for earlier diagnoses

Cortical thickness did not unfailingly identify female or male brains, but the researchers found a constellation of sex-related brain structure differences, and based on this, they were able to separate males from females in most cases.

“Overall, our approach was approximately 74% accurate in predicting biological sex based on brain anatomy,” Ecker said.

Further analyzing the data, Ecker and her colleagues discovered that the probability of autism increased significantly among the participants, whether male or female, whose brain phenotype was more typical of males.

In fact, female participants with brain anatomy more typical of males were three times more likely to have autism than females with a more typical brain.

With this approach, autism risk could be estimated “for individuals based on how characteristically female or male their brain is,” Ecker explained. Though she and her colleagues have examined only adult brains so far, Ecker said “in future research, we are hoping to apply our approach to younger age groups as well.”

Early use of this method in a child’s life could offer earlier diagnosis among those who might then benefit from earlier intervention, she said. Early training is known to have the best results for normalizing children with autism.

According to Dr. Tuong-Vi Nguyen, an assistant professor at McGill University in Montreal, the new study is “provocative” with “good methodology.”

Nguyen, who was not involved in the current study, has investigated the sex-specific effects of testosterone on brain structure between ages 4 and 24.

“Given that the authors’ predominant theory is that a male-typic brain represents a predisposition to autism, their results only partially confirm this,” she said.

She suggested a more conservative rephrasing of the new study’s main finding: “Female, high-functioning individuals with autism spectrum disorder (a very small portion of the overall autism spectrum disorder population), have an increased likelihood of showing a male-typic pattern of brain structure, more specifically, male-typic patterns of cortical thickness.”

She cites the fact that “there was no significant decrease in autism spectrum disorder risk if males had a more female-typic brain structure.”

“It is definitely too early to say if these neuroimaging tools could be used clinically to predict” autism spectrum disorder, she said, adding that “no change to current clinical management can be derived from the results of this study.”