Summary: Researchers found significant gender differences in brain development between boys and girls with autism aged 2 to 13. The study found that autistic girls have thicker cortex at age 3 and more rapid cortical thinning in middle childhood than boys.
This research highlights the need for more inclusive studies to fully understand autism. Biological differences, in addition to underdiagnosis, contribute to gender bias in autism diagnoses.
Highlights:
- Autistic girls have a thicker cortex at age 3 than non-autistic girls.
- Cortical thinning in autistic girls occurs more rapidly than in autistic boys until mid-childhood.
- The study highlights the importance of including both sexes in longitudinal autism research.
Source: University of California, Davis
A new study by UC Davis researchers reveals widespread differences in brain development between boys and girls with autism ages 2 to 13.
The study, published recently in Molecular Psychiatrydiscovered sex-specific changes in the thickness of the outer layer of the brain, called the cortex.
The results are notable because very few studies have looked at cortical development in autistic girls, who are less often diagnosed with autism than men. Nearly four men are diagnosed with autism for every woman.
“It is clear that this gender bias is due, in part, to the underdiagnosis of autism in women,” said Christine Wu Nordahl, professor in the Department of Psychiatry and Behavioral Sciences and the UC Davis Institute. MIND and lead author of the article. . “But this study suggests that diagnostic differences are not a complete explanation: biological differences also exist.”
The outer layer of the brain, the cortex, is made up of distinct layers made up of millions of neurons. These synchronize, allowing us to think, learn, solve problems, create memories and experience emotions. Until about age 2, the cortex thickens rapidly as new neurons are created. After this peak, the outer cortical layer thins.
Previous studies have shown that this thinning process is different in autistic and non-autistic children, but it has not been examined whether autistic boys and girls share the same differences.
“It is important to know more about how sex differences in brain development may interact with the development of autism and lead to different developmental outcomes in boys and girls,” explained Derek Andrews, lead author of the study and assistant project investigator in the Department of Psychiatry and Behavioral Sciences and the MIND Institute.
A changing cortex in childhood
The research team studied brain scans of 290 autistic children – 202 males and 88 females, and 139 typically developing, non-autistic individuals – 79 males and 60 females. They used sex assigned at birth to categorize children.
All participants were part of the MIND Institute’s Autism Phenome Project (APP), one of the largest longitudinal studies of autism in the world.
The project includes the Girls with Autism Imaging of Neurodevelopment (GAIN) study, launched to increase the number of women represented in research. Researchers performed MRI scans at up to four periods between ages 2 and 13.
They found that by age 3, autistic girls had thicker cortex than non-autistic girls of the same age, accounting for about 9% of the total cortical surface area. The differences between autistic and non-autistic men of the same age were much less widespread.
Additionally, compared to males, autistic females had faster rates of cortical thinning through mid-childhood. Cortical differences were present across multiple neural networks.
“We found differences in the brain associated with autism in almost every brain network,” Andrews said.
He noted that it was surprising at first that the differences were greater at younger ages. Because autistic girls showed a faster rate of cortical thinning, by middle childhood the differences between autistic males and females were much less pronounced.
“We generally think that gender differences are greater after puberty. However, brain development between ages 2 and 4 is very dynamic, so small changes in developmental timing between the sexes could lead to large differences that then converge later,” Andrews explained.
The importance of long-term studies of both sexes
These results clearly show that longitudinal studies including both sexes are needed, Nordahl said.
“If we had only looked at the 3-year-old boys, we might have concluded that there was no difference. If we had both boys and girls, but only studied the differences at age 11, we could have concluded that there were very few sex differences in the cortex. We had to follow the boys and girls throughout development to get the whole picture,” she explained.
This is why Nordahl, who now heads the APP, launched the GAIN study in 2014. “The APP had an extremely large sample of around 150 autistic boys, but only around 30 girls autistic.
There were too few autistic girls to really examine how they might be similar or different from boys, so we worked to increase the representation of autistic women in our research,” she said.
GAIN is unique, and Andrews said he hopes other researchers follow suit by including more autistic girls in autism research.
“Autistic women represent approximately 20% of the autistic population. Any successful effort to understand autism will need to include autistic women.
Co-authors of the study include Kersten Diers and Martin Reuter of the German Center for Neurodegenerative Diseases; Devani Cordero of Massachusetts General Hospital; and Joshua K. Lee, Danielle J. Harvey, Brianna Heath, Sally J. Rogers, Marjorie Solomon and David Amaral of UC Davis.
Funding: The study was supported by the National Institute of Mental Health (R01MH127046, R01MH128814, and R01MH103284), the National Institute of Child Health and Development (P50 HD093079), and the Center for Research on Intellectual Disabilities and Developmental Studies of the MIND Institute (P50 HD103526).
About this autism research news
Author: Marianne Sharp
Source: University of California, Davis
Contact: Marianne Sharp – UC Davis
Picture: Image is credited to Neuroscience News
Original research: Free access.
“Sex differences in cortical developmental trajectories in autistic children aged 2 to 13 years” by Christine Wu Nordahl et al. Molecular Psychiatry
Abstract
Gender differences in cortical development trajectories in children with autism aged 2–13 years
Previous studies have reported alterations in cortical thickness in autism. However, few have included enough autistic females to determine whether there are sex-specific differences in the cortical structure of autism.
This longitudinal study aimed to investigate autistic gender differences in cortical thickness and cortical thinning trajectory across childhood.
Participants included 290 autistic individuals (88 females) and 139 non-autistic individuals (60 females) assessed at up to 4 time points spanning approximately 2 to 13 years (918 total MRI time points).
Estimates of cortical thickness during early and late childhood and the trajectory of cortical thinning were modeled using spatiotemporal age-by-sex linear mixed effects models. by diagnosis.
Additionally, the spatial correspondence between cortical maps of sex differences by diagnosis and neurotypical sex differences was assessed. Compared to their non-autistic peers, autistic women showed more widespread cortical differences than autistic men.
These differences involved multiple functional networks and were primarily characterized by thicker cortex at approximately 3 years of age and more rapid cortical thinning in autistic females.
Cortical regions in which autistic alterations differed by sex overlapped significantly with regions differing by sex in neurotypical development.
Autistic women and men demonstrated some common differences in cortical thickness and rates of cortical thinning during childhood compared to their non-autistic peers, but these areas were relatively small compared to the generalized differences observed. between the sexes.
These findings support evidence for 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.