Resume: Researchers found significant sex-specific differences in brain development between autistic boys and girls aged 2 to 13. The study found that autistic girls have a thicker cortex at age 3 and faster cortical thinning in middle age compared to 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.
Key Facts:
- 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 in middle childhood.
- The study highlights the importance of including both genders in longitudinal autism research.
Source: UC Davis
A new study led by UC Davis researchers finds widespread differences in brain development between autistic boys and girls ages 2 to 13.
The research, recently published in Molecular psychiatryfound sex-specific changes in the thickness of the outermost layer of the brain, called the cortex.
The findings are notable because so few studies have examined cortical development in autistic girls, who are less likely to be diagnosed with autism than men. Nearly four men for every woman are diagnosed with autism.
“It is clear that these gender biases are partly due to the underdiagnosis of autism in women,” said Christine Wu Nordahl, professor in the Department of Psychiatry and Behavioral Sciences and the UC Davis MIND Institute and senior author of the paper. . “But this study suggests that differences in diagnosis are not the whole story – biological differences also exist.”
The outer layer of the brain, the cortex, consists of several layers consisting of millions of neurons. These fire in sync with each other, allowing us to think, learn, solve problems, build memories and experience emotions. Until about the age of 2 years, the cortex thickens rapidly as new neurons are produced. After this peak, the outer cortical layer becomes thinner.
Previous studies have shown that this thinning process occurs differently in autistic children than in non-autistic children, but whether autistic boys and girls share the same differences had not been investigated.
“It is important to learn 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,” explains Derek Andrews, lead author of the study and assistant project scientist at the Department of Psychiatry and Psychiatry. Behavioral Sciences and at the MIND Institute.
A changing cortex in childhood
The research team studied the brain scans of 290 autistic children – 202 men and 88 women, and 139 non-autistic, typically developing individuals – 79 men and 60 women. They used gender assigned at birth to categorize the children.
All participants took part in the MIND Institute’s Autism Phenome Project (APP), one of the largest longitudinal autism studies in the world.
The project includes the Girls with Autism Imaging of Neurodevelopment (GAIN) study, which was launched to increase the number of women represented in research. The researchers made MRI scans at a maximum of four time points between the ages of 2 and 13 years.
They found that at age 3, autistic girls had a thicker cortex than non-autistic girls of the same age, covering about 9% of the total cortical surface area. Differences between autistic men and non-autistic men of the same age were much less widespread.
Furthermore, compared to men, autistic women had faster cortical thinning until mid-childhood. The cortical differences were present in multiple neural networks.
“We found differences in the brain associated with autism in almost all networks in the brain,” Andrews said.
He noted that it was initially a surprise that the differences were greatest at a younger age. Because autistic girls showed a faster rate of cortical thinning, the differences between autistic men and women were much less pronounced by mid-childhood.
“We usually think that gender differences are greater after puberty. However, brain development around the age of 2 to 4 is very dynamic, so small changes in the timing of development between the sexes can result in large differences that converge later,” Andrews explains.
The importance of long-term studies of both sexes
These findings make it clear that longitudinal studies involving both sexes are necessary, Nordahl said.
“If we had only looked at boys at age three, we might have concluded that there were no differences. If we had both boys and girls, but only examined the differences at age 11, we might have concluded that there were very few sex differences in the cortex. We had to follow both boys and girls through development to see the full picture,” she explains.
This was why Nordahl, who now heads the APP, launched the GAIN study in 2014. “The APP had a wonderfully large sample of about 150 autistic boys, but only about 30 autistic girls.
There were too few autistic girls to really investigate the extent to which they resemble or differ from boys. That’s why we’ve done our best to increase the representation of autistic women in our research,” she said.
GAIN is unique, and Andrews said he hopes other researchers will follow suit by involving more autistic girls in autism research.
“Autistic women represent approximately 20% of the autistic population. Any successful effort to understand autism will have to include autistic women.”
Co-authors of the study include Kersten Diers and Martin Reuter from 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.
Financing: 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 MIND Institute Intellectual and Developmental Disabilities Research Center (P50 HD103526).
About this autism research news
Author: Marianne Sharp
Source: UC Davis
Contact: Marianne Sharp – UC Davis
Image: The image is credited to Neuroscience News
Original research: Open access.
“Sex differences in trajectories of cortical development in autistic children aged 2 to 13 years” by Christine Wu Nordahl et al. Molecular psychiatry
Abstract
Gender differences in trajectories of cortical development in autistic children aged 2 to 13 years
Previous studies have reported changes in cortical thickness in autism. However, few have included enough autistic women to determine whether there are sex-specific differences in cortical structure in autism.
This longitudinal study aimed to investigate autistic sex differences in cortical thickness and the trajectory of cortical thinning during childhood.
Participants included 290 autistic (88 female) and 139 non-autistic (60 female) individuals, assessed at up to 4 time points spanning ~2–13 years of age (918 MRI time points in total).
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.
Furthermore, the spatial correspondence between cortical maps of sex-by-diagnosis differences and neurotypical sex differences was evaluated. Compared to their non-autistic peers, autistic women had more extensive cortical differences than autistic men.
These differences involved multiple functional networks and were mainly characterized by a thicker cortex at ~3 years of age and faster cortical thinning in autistic females.
Cortical regions in which autistic changes differed between sexes overlapped significantly with regions that differed by sex in neurotypical development.
Autistic women and men showed some shared differences in cortical thickness and rates of cortical thinning in childhood compared to their non-autistic peers, but these areas were relatively small compared to the widespread differences observed between the sexes.
These results support evidence of sex-specific neurobiology in autism and suggest that processes regulating sex differentiation in the neurotypical brain contribute to sex differences in the etiology of autism.