Key differences in brain development: autism research
The Sector > Research > Key differences in brain development between autistic boys and girls

Key differences in brain development between autistic boys and girls

by Freya Lucas

June 13, 2024

A new study has found widespread differences in brain development between autistic boys and girls aged between 2 and 13 years of age. 


The study, published recently in Molecular Psychiatry, found sex-specific changes in the thickness of the outer layer of the brain, called the cortex.


The brain’s outer layer, the cortex, is made up of distinct layers composed of millions of neurons. These fire in sync together, allowing people to think, learn, solve problems, build memories, and experience emotions. 


Up until 2 years of age, the cortex rapidly thickens as new neurons are created. After this peak, the outer cortical layer thins. Previous studies have found that this thinning process is different in autistic children than non-autistic children, but whether autistic boys and girls share the same differences has not been examined.  


The findings are notable because so few studies have addressed cortical development in autistic girls, who are diagnosed with autism less often than males. Nearly four males are diagnosed with autism for every one female.


“It is clear that this sex bias is due, in part, to underdiagnosis of autism in females,” senior author Professor Christine Wu Nordahl said, “but this study suggests that differences in diagnosis are not the full story — biological differences also exist.”


Brain regions associated with autism showed different rates of cortical thinning in males and females, similar to regions that show sex differences in cortical thinning in typical development.


“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,” lead author Derek Andrews explained.


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 sex assigned at birth to categorize the children.


All were participants 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, launched to increase the number of females represented in research. The researchers took MRI scans at up to four time periods between the ages of 2 and 13 years.


They found that at age 3 years, autistic girls had a thicker cortex than non-autistic girls of the same age, comprising about 9 per cent of the total cortical surface. Differences in autistic males when compared to non-autistic males of the same age were much less widespread.


In addition, when compared to males, autistic females had faster rates of cortical thinning into middle childhood. The cortical differences were present across multiple neural networks.


“We found differences in the brain associated with autism across nearly all networks in the brain,” Mr Andrews said.


He noted that it was a surprise at first that the differences were greatest at younger ages. Because autistic girls had a more rapid rate of cortical thinning, by middle childhood, the differences between autistic males and females were much less pronounced.


“We typically think of sex differences as being larger after puberty. However, brain development around the ages of 2-4 years is highly dynamic, so small changes in timing of development between the sexes could result in large differences that then converge later,” Mr Andrews explained.


These findings make it clear that longitudinal studies that include both sexes are necessary, Professor Nordahl said.


“If we had only looked at boys at age 3 years, we may have concluded that there were no differences. If we had both boys and girls, but only investigated differences at 11 years of age, we may have concluded that there were very few sex differences in the cortex. We needed to follow both boys and girls across development to see the full picture,” she explained.  


Co-authors on 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, David Amaral and Christine Wu Nordahl of UC Davis.


Read the full paper here. 

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