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There are critical differences in the brains of girls diagnosed with autism

From the time you’re born until about age 2, the outer layer of your brain — the cortex — rapidly thickens in a frenzy of neuron creation. After all that excitement, that dense tangle of nerve cells was trimmed back in a process called “cortical thinning.”

Now, a new study has found some key differences in how this process occurs in children with autism, depending on their gender at birth.

Previous studies have found variations in how the brains of children with autism undergo cortical thinning, but so far the picture has been hazy and controversial. This is partly because research on autism spectrum disorder has historically underrepresented females, and this is true for research on cortical development.

“It’s clear that this sex bias is partly due to the underdiagnosis of autism in women,” says neuroscientist Christine Wu Nordahl of the University of California, Davis. “But this study suggests that differences in diagnosis aren’t the whole story—biological differences also exist.”

Although the actual ratio is likely to be much lower, only one woman is diagnosed with autism for about every four men who receive a diagnosis, hinting at the possibility that gender may influence the development of the condition.

By including both autistic and non-autistic children in the study, researchers could compare differences in autism-related cortical thickness within each birth sex group (for example, the difference between autistic and non-autistic females ), as well as to compare outcomes for autism groups based only on sex at birth.

The study involved brain scans of 290 children with autism (202 males, 88 females) and 139 children without autism (79 males, 60 females) with typical development.

These scans were collected up to four times for each child between the ages of 2 and 13, offering a detailed picture of children’s cortical development from the age when the cortex is thickest to the age when thinning is most rapid, typically around 14 years.

At age 3, certain areas of the cortex—about 9 percent of its total surface area—were thicker among females with autism than undiagnosed peers of the same age and sex. In the male group at age 3, there were few significant differences in cortical thickness between autistic and non-autistic children.

By age 11, cortical gender differences are much more difficult to discern. The main differences revealed in the study are only visible as changes in the cortex over time.

Compared to their non-autistic counterparts, female children with autism had faster cortical thinning in certain regions during childhood, while male children with autism had faster thinning than non-autistic males overall. These changes are not consistent throughout the brain: only in certain cortical regions that make up less than 5 percent of its totality, including the networks that plan and control motor tasks, maintain attention, and solve problems, and the brain “radar” that helps us direct our attention when our conditions change.

In other regions, such as the limbic network, where behavioral and emotional responses occur, cortical thinning occurred more rapidly in autistic males compared to non-autistic males and less rapidly in autistic females compared to non-autistic females.

There are many reasons why a person’s biology can be linked to or reflect which sex they were assigned at birth, and this is not necessarily fixed: certain traits can be linked to the X- or Y-chromosome, while others influence from different hormone levels or may even be the result of cultural attitudes towards gender and sex that lead to different behaviors and lifestyles.

So while this study found visible differences between the male and female groups, more detailed research will be needed to understand exactly how these differences occur and what this might mean for transgender, nonbinary, or intersex people with autism.

This nuance is particularly relevant here given that gender-queer adults are up to six times more likely to be diagnosed with autism than cisgender adults (those who identify with their sex and gender assigned at birth) .

“Typically, we think of gender differences as being larger after puberty. However, brain development between the ages of 2 and 4 is highly dynamic, so small changes in the timing of development between the sexes can lead to large differences that then converge later,” says psychiatric researcher Derek Andrews from the University of California, Davis.

“It is important to learn more about how gender differences in brain development may interact with autistic development and lead to different developmental outcomes in boys and girls.”

This research was published in Molecular psychiatry.

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