From the moment you were born until about age 2, your brains' outer layer – the cortex – rapidly thickened in a frenzy of neuron creation. After all that excitement, that dense hedge 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 autistic children, depending on their birth sex.
Previous studies have found variations in the way autistic children's brains undergo cortical thinning, but so far the picture is hazy and inconsistent. This is partly because historically, studies into autism spectrum disorder under-represent the female sex, and that goes for research into cortical development.
"It is clear that this sex bias is due, in part, to under-diagnosis of autism in females," says neuroscientist Christine Wu Nordahl from the University of California Davis. "But this study suggests that differences in diagnosis are not the full story – biological differences also exist."
Though the actual ratio is likely to be a lot lower, only one female is diagnosed with autism for roughly every four males that receive a diagnosis, hinting at the possibility of sex influencing the condition's development.
By including both autistic and non-autistic children in the study, the researchers could compare differences in cortical thickness associated with autism within each birth sex group (for instance, the difference between autistic females and non-autistic females), as well as comparing results for the autistic groups on the basis of birth sex alone.
The study included brain scans from 290 autistic children (202 males, 88 females) and 139 non-autistic children (79 males, 60 females) with typical development.
These scans were collected up to four times for each child, from ages 2 to 13, offering a detailed picture of the childrens' cortical development from the age when the cortex is at its thickest, up to the age where thinning is at its most rapid, usually around 14 years.
At age 3, certain regions of the cortex – about 9 percent of its total surface – were thicker among autistic females than peers without a diagnosis 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 differences between sexes were much harder to spot. The main distinctions revealed in the study were only visible as changes to the cortex across time.
Compared to their non-autistic counterparts, female children with autism had more rapid cortical thinning in certain regions across childhood, while autistic males had less rapid thinning than non-autistic males overall. These changes weren't consistent across the entire brain: only in certain cortical regions that make up less than 5 percent of its entirety, including the networks that plan and control motor tasks, sustain attention and solve problems, and the brain's 'radar' which helps us to pivot attention when our conditions change.
In other regions, like the limbic network, where behavioral and emotional responses arise, cortex 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 a person's biology may relate to or reflect which sex they are assigned at birth, and it's not necessarily fixed: certain traits can be X- or Y-chromosome linked, while others are affected by different hormone levels, or can even be the result of cultural attitudes towards assigned sex and gender that lead to different behaviors and lifestyles.
And so while this study has found observable differences between the male and female groups, more detailed research will be required to understand exactly how these differences arise, and what it may mean for transgender, nonbinary, or intersex people with autism.
That nuance is particularly relevant here, given that gender diverse adults are up to six times more likely to be diagnosed autistic than cisgender adults (those who identify with their gender and sex assigned at birth).
"We typically think of sex differences as being larger after puberty. However, brain development around the ages of 2 to 4 is highly dynamic, so small changes in timing of development between the sexes could result in large differences that then converge later," says psychiatric researcher Derek Andrews from the University of California Davis.
"It's important to learn more about how sex 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.
https://www.sciencealert.com/there-are-critical-differences-in-the-brains-of-girls-diagnosed-with-autism
Andrews DS, Diers K, Lee JK, Harvey DJ, Heath B, Cordero D, Rogers SJ, Reuter M, Solomon M, Amaral DG, Nordahl CW. Sex differences in trajectories of cortical development in autistic children from 2-13 years of age. Mol Psychiatry. 2024 May 16. doi: 10.1038/s41380-024-02592-8. Epub ahead of print. PMID: 38755243.
Abstract
Previous studies have reported alterations in cortical thickness in autism. However, few have included enough autistic females to determine if there are sex specific differences in cortical structure in autism. This longitudinal study aimed to investigate autistic sex differences in cortical thickness and trajectory of cortical thinning across childhood. Participants included 290 autistic (88 females) and 139 nonautistic (60 females) individuals assessed at up to 4 timepoints spanning ~2-13 years of age (918 total MRI timepoints). Estimates of cortical thickness in early and late childhood as well as the trajectory of cortical thinning were modeled using spatiotemporal linear mixed effects models of age-by-sex-by-diagnosis. Additionally, the spatial correspondence between cortical maps of sex-by-diagnosis differences and neurotypical sex differences were evaluated. Relative to their nonautistic peers, autistic females had more extensive cortical differences than autistic males. These differences involved multiple functional networks, and were mainly characterized by thicker cortex at ~3 years of age and faster cortical thinning in autistic females. Cortical regions in which autistic alterations were different between the sexes significantly overlapped with regions that differed by sex in neurotypical development. Autistic females and males demonstrated some shared differences in cortical thickness and rate of cortical thinning across childhood relative to their nonautistic peers, however these areas were relatively small compared to the widespread differences observed across the sexes. These results support evidence of sex-specific neurobiology in autism and suggest that processes that regulate sex differentiation in the neurotypical brain contribute to sex differences in the etiology of autism.
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