A study of about 800 children with autism found gender differences in a core feature of the disorder, as well as in the youngsters’ brain structures.

Girls with autism display less repetitive and restricted behavior than boys do, according to a study by researchers at the Stanford University School of Medicine.

The study also found that brain differences between boys and girls with autism help explain this discrepancy.

The study, published online Sept. 3 in Molecular Autism, gives the best evidence to date that boys and girls exhibit the developmental disorder differently.

“We wanted to know which specific clinical manifestations of autism show significant gender differences, and whether patterns in the brain’s gray matter could explain behavioral differences,” said the study’s senior author, Vinod Menon, PhD, professor of psychiatry and behavioral sciences. Knowledge of the difference could help clinicians better recognize and treat autism in both sexes, he added. “Understanding this is really quite crucial clinically.”

“We found strong evidence for gender differences in autism,” said postdoctoral scholar Kaustubh Supekar, PhD, the study’s lead author. The researchers used two large, public databases to examine nearly 800 children with high-functioning forms of autism in the United States, he said.

Repetitive and restricted behavior is perhaps the most widely recognized of the three core features of autism. It can show up as a child’s preoccupation with a narrow interest, inflexibility about routines or repetitive motions such as hand-flapping. The other core features of autism are social and communication deficits.

More boys with high-functioning autism

Among children diagnosed with the high-functioning form of autism, boys outnumber girls by four to one. Scientists were interested in comparing the expression of core features of the disorder between sexes because they have long suspected girls with autism may display symptoms differently, causing them to be underdiagnosed or making it harder for them to get the most appropriate treatment.

“Autism has primarily been studied from the viewpoint of boys with the disorder,” said Menon, who holds the Rachael L. and Walter F. Nichols, MD, Professorship. “Understanding gender differences can help in identifying the behavioral skills that are most important to remediate in girls vis-a-vis boys.”

The study examined the severity of autism symptoms in 128 girls and 614 boys registered with the National Database for Autism Research. The children ranged in age from 7 to 13, had IQ scores above 70, and had been evaluated with standard tests for autistic behavior. The boys and girls were matched for age, and had the same average IQ. Girls and boys had similar scores for social behavior and communication. Girls and boys had similar scores for social behavior and communication. But girls had lower (more normal) scores on a standard measurement of repetitive and restricted behaviors.

The researchers then examined data from the Autism Brain Imaging Data Exchange that included structural MRI brain scans of 25 boys with autism, 25 girls with autism, 19 typically developing boys and 19 typically developing girls. The individuals among the groups were matched for age and IQ. The researchers again found that girls and boys did not differ on social behavior and communication skills, but that girls had less-severe repetitive and restricted behaviors. “This replication provides the strongest evidence to date for gender differences in a core phenotypic feature of autism,” Menon said.

Brain-structure differences

The brain-scan analysis revealed several gender differences in brain structure between typically developing boys and girls, consistent with the findings of earlier studies.

Children with autism, however, had a dissimilar set of gender differences in their brains — specifically, in the motor cortex, supplementary motor area and a portion of the cerebellum. These regions affect motor function and planning of motor activity. The researchers noted that many repetitive behaviors, such as hand-flapping, have a motor component. The study demonstrated that patterns of gray matter in these motor regions could accurately distinguish girls from boys with autism, Supekar said. The researchers found that parts of the motor system that contributed to individual scores for repetitive and restricted behaviors were different in boys and girls.

“Girls and boys with autism differ in their clinical and neurobiological characteristics, and their brains are patterned in ways that contribute differently to behavioral impairments,” Menon said.

“The discovery of gender differences in both behavioral and brain measures suggests that clinicians may want to focus diagnosis and treatments for autistic girls differently than boys,” Supekar added.

About this autism research

Funding: This research was supported by a NARSAD Young Investigator Award, an Atherton Investigator Award, the National Institutes of Health (grant MH084164) and the Simons Foundation.

Creation of the ABIDE data set was supported by the National Institute of Mental Health (grants K23MH087770 and R03MH096321), the Leon Levy Foundation, Joseph P. Healy, and the Stavros Niarchos Foundation. Menon is a member of the Stanford Child Health Research Institute.

Stanford’s Department of Psychiatry and Behavioral Sciences also supported the research.

Source: Erin Digitale – Stanford

Image Source: The image is credited to Schaer et al./Molecular Autism and is licensed CC BY 4.0

Original Research: Full open access research for “Sex differences in cortical volume and gyrification in autism” by Marie Schaer, John Kochalka, Aarthi Padmanabhan, Kaustubh Supekar, and Vinod Menon in Molecular Autism. Published online July 4 2015 doi:10.1186/s13229-015-0035-y

Abstract

Sex differences in cortical volume and gyrification in autism

Background

Male predominance is a prominent feature of autism spectrum disorders (ASD), with a reported male to female ratio of 4:1. Because of the overwhelming focus on males, little is known about the neuroanatomical basis of sex differences in ASD. Investigations of sex differences with adequate sample sizes are critical for improving our understanding of the biological mechanisms underlying ASD in females.

Methods

We leveraged the open-access autism brain imaging data exchange (ABIDE) dataset to obtain structural brain imaging data from 53 females with ASD, who were matched with equivalent samples of males with ASD, and their typically developing (TD) male and female peers. Brain images were processed with FreeSurfer to assess three key features of local cortical morphometry: volume, thickness, and gyrification. A whole-brain approach was used to identify significant effects of sex, diagnosis, and sex-by-diagnosis interaction, using a stringent threshold of p < 0.01 to control for false positives. Stability and power analyses were conducted to guide future research on sex differences in ASD.

Results

We detected a main effect of sex in the bilateral superior temporal cortex, driven by greater cortical volume in females compared to males in both the ASD and TD groups. Sex-by-diagnosis interaction was detected in the gyrification of the ventromedial/orbitofrontal prefrontal cortex (vmPFC/OFC). Post-hoc analyses revealed that sex-by-diagnosis interaction was driven by reduced vmPFC/OFC gyrification in males with ASD, compared to females with ASD as well as TD males and females. Finally, stability analyses demonstrated a dramatic drop in the likelihood of observing significant clusters as the sample size decreased, suggesting that previous studies have been largely underpowered. For instance, with a sample of 30 females with ASD (total n = 120), a significant sex-by-diagnosis interaction was only detected in 50 % of the simulated subsamples.

Conclusions

Our results demonstrate that some features of typical sex differences are preserved in the brain of individuals with ASD, while others are not. Sex differences in ASD are associated with cortical regions involved in language and social function, two domains of deficits in the disorder. Stability analyses provide novel quantitative insights into why smaller samples may have previously failed to detect sex differences.

“Sex differences in cortical volume and gyrification in autism” by Marie Schaer, John Kochalka, Aarthi Padmanabhan, Kaustubh Supekar, and Vinod Menon in Molecular Autism. Published online July 4 2015 doi:10.1186/s13229-015-0035-y

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