Brain Study Suggests Autism Develops Differently in Girls Than Boys

Autism spectrum disorder is four times more common in boys, which may help explain why there’s far less research about autism in girls.

New research has shed light on how autism-spectrum disorder manifests in the brains of girls,

The researchers discovered that there is a significant difference in the genes and “genetic burden” that underpin the condition in girls and boys. They also identified specific ways the brains of girls with ASD respond differently to social cues such as facial expressions and gestures than do those of girls without ASD.

The new insights come from a sweeping research project, led by Pelphrey, the Harrison-Wood Jefferson Scholars Foundation Professor at UVA. It brings together expertise from Yale University; Harvard University; the University of California, Los Angeles; Children’s National; the University of Colorado, Denver; and Seattle Children’s. At UVA, key players included both Pelphrey, of the School of Medicine’s Department of Neurology and the School of Education and Human Development, and John D. Van Horn, of the School of Data Science and the Department of Psychology.

The research combined cutting-edge brain imaging with genetic research to better understand ASD’s effects in girls. Those effects have remained poorly explored because the condition is four times more common in boys

Pelphrey and colleagues used functional magnetic-resonance imaging to examine brain activity during social interactions. They found that autistic girls used different sections of their brains than girls who did not have ASD. And, most surprisingly, the difference between girls with and without autism was not the same as the difference in the brain seen when comparing boys with and without autism, revealing different brain mechanisms at play in autism depending on a person’s gender.

Likewise, the underlying genetic contributors were quite different, the researchers found. Girls had much larger numbers of rare variants of genes active during the early development of a brain region known as the striatum. This suggests that the effects on the striatum may contribute to ASD risk in girls. (Scientists believe a section of the striatum, called the putamen, is involved in interpreting both social interaction and language.)

“The convergence of the brain imaging and genetic data provides us with an important new insight into the causes of autism in girls,” Pelphrey said. “We hope that by working with our colleagues in UVA’s Supporting Transformative Autism Research, we will be able to leverage our findings to generate new treatment strategies tailored to autistic girls.”

The new findings lend support to the idea that autism has sex-specific biological roots. Such a difference may help explain the lower prevalence of autism in girls — and compound a diagnostic bias that leads some clinicians to overlook girls with the condition.

Autism appears to develop differently in girls and boys, so the findings of research conducted mainly with boys might not apply to girls, a new study suggests.

For the study, the researchers combined brain imaging with genetic investigation to learn more about autism in girls

Evaluating Brain Structure

Functional MRI was used to examine brain activity during social interactions. It showed that girls with autism use different sections of their brains than girls without autism.

The difference between girls with and without autism was not the same as the difference between boys with and without autism, meaning that brain mechanisms involved in autism vary depending on gender, according to the study authors

The investigators also found that girls with autism had much larger numbers of rare variants of genes active during early development of a brain region called the striatum. A section of the striatum is believed to be involved in interpreting social interaction and language.

In the latest study, the researchers noted that different areas of the brain are affected in girls and boys with autism. In girls, the changes are seen in an area called the striatum, whereas boys with autism have changes in the temporal lobe

When researchers compared the fMRI results of the girls and boys in both the ASD and non-ASD groups, they found that the girls with ASD showed markedly reduced responses in the sensorimotor, striatal, and frontal regions of the brain compared to the girls without ASD.

The findings were published April 16 in the journal Brain

Evaluating Genetics

For the second part of the study, the researchers looked at the results of genetic analysis on the boys and girls. They found that girls with ASD had more rare gene variants—which are typically expressed from a few weeks of conception to age 2— that are linked to the striatum of the brain.

The researchers noted that the striatum was also one of the areas of the brain that showed differences in the fMRI scans of the girls with ASD

Many factors contribute to the difference in diagnosing ASD between boys and girls, from how clinicians assess the condition to the type of symptoms associated with it.

SUMMERY:

New research shows that girls with autism spectrum disorder (ASD) appear to have more genetic mutations than boys with ASD. Girls also show differences in brain structure and function.

Girls with autism may have changes in a different area of the brain (the striatum) than boys with autism (who typically have changes in the brain’s temporal lobe).