Summary: Researchers at UC Davis report clear sex-specific differences in cortical development between autistic boys and girls aged 2–13. The study shows that autistic girls tend to have a thicker cortex around age 3 and then experience faster cortical thinning through middle childhood compared with autistic boys. These biological differences, alongside underdiagnosis, help explain the male-female disparity in autism diagnoses.
The findings underscore the importance of including both sexes in longitudinal autism research to accurately capture developmental trajectories and to better understand how sex-specific neurobiology relates to behavioral outcomes.
Key facts:
- At about age 3, autistic girls showed a thicker cortex than non-autistic girls, affecting roughly 9% of the cortical surface.
- Autistic girls exhibited a faster rate of cortical thinning into middle childhood than autistic boys.
- These cortical differences spanned multiple brain networks, highlighting the need for long-term studies that include both sexes.
Source: UC Davis
Overview
A new longitudinal study led by researchers at UC Davis examined how cortical development differs by sex in autistic children between the ages of 2 and 13. Published in Molecular Psychiatry, the research focused on cortical thickness — the measure of the brain’s outer layer where neurons and their connections support cognition, memory, emotion and learning.
“It is clear that this sex bias is due, in part, to underdiagnosis of autism in females,” said Christine Wu Nordahl, professor in the Department of Psychiatry and Behavioral Sciences and the UC Davis MIND Institute, and a senior author on the paper. “But this study suggests that differences in diagnosis are not the full story — biological differences also exist.”
The cortex thickens rapidly in early life, peaking around age 2, then typically thins as development proceeds. Prior research has shown that cortical thinning follows different patterns in autistic children compared with non-autistic children, but few studies have had enough autistic females to explore whether boys and girls show distinct patterns. This study addressed that gap.
“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,” said Derek Andrews, lead author and assistant project scientist in the Department of Psychiatry and Behavioral Sciences and at the MIND Institute.
Study design and participants
The team analyzed MRI scans from 429 children participating in the MIND Institute’s Autism Phenome Project (APP), which includes the Girls with Autism Imaging of Neurodevelopment (GAIN) initiative started to improve female representation in autism research. The sample comprised 290 autistic children (202 males and 88 females) and 139 non-autistic, typically developing children (79 males and 60 females). Scans were collected at up to four timepoints between ages 2 and 13, yielding 918 MRI timepoints overall. Participants were categorized by sex assigned at birth.
Main findings
At around age 3, autistic girls exhibited a thicker cortex than non-autistic girls, with regional differences that accounted for about 9% of the cortical surface. By contrast, differences between autistic and non-autistic boys at the same age were much less widespread.
Across development, autistic girls showed a faster rate of cortical thinning into middle childhood than autistic boys. These sex-specific differences appeared across multiple functional brain networks rather than being restricted to a single region.
Andrews noted that the largest differences were evident at younger ages and then converged by middle childhood. “We typically think of sex differences as being larger after puberty. However, brain development around the ages of 2–4 is highly dynamic, so small timing differences between the sexes can produce larger early differences that then become less distinct later on,” he said.
Implications and the need for inclusive longitudinal studies
These results highlight why long-term research that intentionally includes autistic females is necessary. Nordahl, who directs the APP, explained that early iterations of the study included many more autistic boys than girls, prompting the launch of GAIN in 2014 to boost female participation. Greater representation of females is essential because autistic females comprise about 20% of the autistic population, and understanding autism requires studying both sexes.
GAIN’s expanded female enrollment allowed the team to detect sex-differentiated developmental patterns that would have been missed in male-dominated samples or in cross-sectional snapshots taken at a single age.
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 work was supported by the National Institute of Mental Health (R01MH127046, R01MH128814 and R01MH103284), the National Institute of Child Health and Human Development (P50 HD093079) and the MIND Institute Intellectual and Developmental Disabilities Research Center (P50 HD103526).
About this autism research news
Author: Marianne Sharp ([email protected])
Source: UC Davis
Contact: Marianne Sharp – UC Davis
Image: Image credited to Neuroscience News
Original research: Open access. “Sex differences in trajectories of cortical development in autistic children from 2–13 years of age” by Christine Wu Nordahl et al., published in Molecular Psychiatry.
Abstract (summary)
Previous studies have identified alterations in cortical thickness associated with autism, but few have included sufficient numbers of autistic females to investigate sex-specific differences. This longitudinal study modeled cortical thickness and trajectories of cortical thinning across childhood in 290 autistic (88 females) and 139 non-autistic (60 females) participants assessed up to four times between approximately 2 and 13 years of age (918 MRI timepoints).
Using spatiotemporal mixed effects models, the authors estimated cortical thickness in early and later childhood and evaluated age-by-sex-by-diagnosis interactions. Relative to non-autistic peers, autistic females showed more extensive cortical differences than autistic males. These differences spanned multiple functional networks and were mainly characterized by thicker cortex around age 3 and faster cortical thinning thereafter in autistic females. Regions showing sex-by-diagnosis differences overlapped significantly with regions that typically differ by sex in neurotypical development.
While autistic females and males shared some cortical alterations relative to their non-autistic peers, those shared regions were relatively small compared with the broader, sex-specific differences observed. The results support the presence of sex-specific neurobiology in autism and suggest that processes governing sex differentiation in the typical brain contribute to sex differences in the origins and development of autism.