Summary: Researchers have discovered significant sex-specific differences in brain development between autistic boys and girls aged 2-13. The study found that autistic girls have a thicker cortex at age 3 and faster cortical thinning in middle childhood compared to boys.
This research highlights the need for more inclusive studies to fully understand autism. Biological differences, in addition to underdiagnosis, contribute to the sex bias in autism diagnoses.
Key facts:
- Autistic girls have a thicker cortex at age 3 compared to non-autistic girls.
- Cortical thinning in autistic girls occurs more rapidly than in autistic boys by middle childhood.
- The study highlights the importance of including both sexes in longitudinal autism research.
Source: UC Davis
A new study led by UC Davis researchers found wide-ranging differences in brain development between autistic boys and girls ages 2-13.
A study published recently in Molecular psychiatryfound sex-specific changes in the thickness of the brain’s outer layer, called the cortex.
The findings are notable because so few studies have looked at cortical development in autistic girls, who are less frequently diagnosed with autism than boys. For every woman, almost four men are diagnosed with autism.
“It’s clear that this sex bias is partly due to the underdiagnosis of autism in women,” said Christine Wu Nordahl, a professor in the Department of Psychiatry and Behavioral Sciences and the UC Davis MIND Institute and lead author of the paper. . “But this study suggests that differences in diagnosis aren’t the whole story—there are also biological differences.”
The outer layer of the brain, the cortex, is made up of distinct layers made up of millions of neurons. These synchronize to allow us to think, learn, solve problems, build memories and experience emotions. By about age 2, the cortex rapidly thickens as new neurons are formed. After this peak, the outer cortical layer becomes thinner.
Previous studies have found that this thinning process differs in autistic children from non-autistic children, but whether autistic boys and girls share the same differences has not been investigated.
“It is important to learn more about how gender differences in brain development may interact with autistic development to lead to different developmental outcomes for boys and girls,” explained Derek Andrews, lead author of the study and assistant research scientist in the Department of Psychiatry and Psychiatry. Behavioral Sciences and at the MIND Institute.
The changing cortex in childhood
The research team studied the brain scans of 290 autistic children – 202 males and 88 females, and 139 non-autistic, typically developing individuals – 79 males and 60 females. They used the gender assigned at birth to categorize the children.
All participants were in 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, which was launched to increase the number of women represented in research. The researchers performed MRI scans at up to four time periods between the ages of 2 and 13.
They found that at age 3, autistic girls had a thicker cortex than age-matched non-autistic girls, accounting for about 9% of the total cortical surface area. Differences in autistic males compared to age-matched non-autistic males were much less widespread.
Additionally, compared to males, autistic females had a faster rate of cortical thinning by middle childhood. Cortical differences were present across several neuronal networks.
“We found brain differences associated with autism in almost every network in the brain,” Andrews said.
He noted that it was initially a surprise that the differences were greatest at younger ages. Because autistic girls had a faster rate of cortical thinning in middle childhood, the differences between autistic males and females were much less pronounced.
“Typically, we think of gender differences as larger after puberty. However, brain development around 2-4 years of age is highly dynamic, so small changes in the timing of development between the sexes could lead to large differences that converge later,” explained Andrews.
Importance of long-term studies of both sexes
These findings make it clear that longitudinal studies that include both sexes are necessary, Nordahl said.
“If we looked only at 3-year-old boys, we could conclude that there are no differences between them. If we had both boys and girls, but only examined differences at age 11, we might conclude that there were very few differences between the sexes in the cortex. We needed to follow both boys and girls across development to see the full picture,” she explained.
That was why Nordahl, who now directs APP, launched the GAIN study in 2014. “APP had an amazingly large sample of about 150 autistic boys, but only about 30 autistic girls.
That was too few autistic girls to really explore how they might be similar or different to 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 will follow suit and include more autistic girls in autism research.
“Autistic women represent about 20% of the autistic population. Any successful effort to understand autism will need to include autistic women.”
Study co-authors 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 MIND Institute’s Mental and Developmental Disabilities Research Center (P50 HD103526)
About this autism research news
Author: Marianne Sharp
Source: UC Davis
Contact: Marianne Sharp – UC Davis
Picture: Image is credited to Neuroscience News
Original Research: Open access.
“Sex Differences in Cortical Developmental Trajectories in Autistic Children Aged 2-13” by Christine Wu Nordahl et al. Molecular psychiatry
Abstract
Gender differences in cortical developmental trajectories in autistic children aged 2–13 years
Previous studies have reported changes in cortical thickness in autism. However, few have included enough autistic females to determine whether there are sex-specific differences in cortical structure in autism.
This longitudinal study aimed to investigate autistic gender differences in cortical thickness and the trajectory of cortical thinning across childhood.
Participants included 290 autistic (88 female) and 139 non-autistic (60 female) individuals assessed at up to 4 time points between the ages of ~2–13 years (918 MRI time points in total).
Estimates of cortical thickness in early and late childhood, as well as trajectories of cortical thinning, were modeled using spatiotemporal linear mixed-effects age-by-sex-by-diagnosis models.
Furthermore, the spatial correspondence between cortical maps of gender differences by diagnosis and neurotypical gender differences was assessed. Compared to non-autistic peers, autistic females had greater 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 changes differed between sexes significantly overlapped with regions that differed by gender in neurotypical development.
Autistic females and males showed some shared differences in cortical thickness and rate of cortical thinning in childhood compared to their non-autistic peers, however, these areas were relatively small compared to the widespread differences observed between the sexes.
These results support evidence for sex-specific neurobiology in autism and suggest that processes that regulate sex differentiation in the neurotypical brain contribute to gender differences in the etiology of autism.