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Solving the Puzzle of Girls with Autism

March 31, 2017

Dr. Pamela Ventola knew that girls are diagnosed with autism in far fewer numbers than boys. And knew that girls with autism generally behave differently than boys with autism. She also knew that a treatment program had demonstrated efficacy in helping boys with autism become more socially engaged and function successfully.

What she did not know was whether girls with autism might also benefit from that same treatment. So with a grant from Women’s Health Research at Yale in 2015, that’s what she set out to do. And according to the results, she now knows that at the end of treatment, the magnitude of improvement was greater for the girls than for the boys.

“We knew that our treatment works,” Ventola said. “I didn’t realize it would work so much better in girls.”

Boys are diagnosed with autism roughly four times as often as girls, a discrepancy that isn’t fully understood or even widely studied. The little research available shows that girls with autism appear to be lower functioning in terms of their IQ. But some of the higher functioning girls are more socially interested and chatty than boys and so might not be diagnosed as having autism.

About one in 68 American children have been diagnosed as appearing somewhere on a broadly defined autism spectrum. Ventola, an Assistant Professor at the Yale Child Study Center, designed a study in which 21 girls and 24 boys with autism would undergo four months of Pivotal Response Therapy, or PRT, participating in play-based sessions with a therapist who rewards certain social goals. The children might get to play a game they like if, for example, they make eye contact or engage in a backand-forth conversation rather than voice an inner monologue.

At the start of the study, the girls displayed lower functioning than the boys, showing lower scores on measures of adaptive communication, socialization, and daily living skills that required more support from caregivers. And though they were more impaired at the beginning, the girls made larger gains than the boys over the course of the treatment.

“The girls were worse off than the boys in terms of their behavior,” Ventola said. “At the end there was no difference. They didn’t catch up to typically developing children; they still have autism. But they caught up to the boys with autism.”

For Ventola, the results underscore a need to treat girls regardless of their age and the severity of their impairments.

“These girls are not newborns,” she said. “They’ve had up to nine years for potential improvement and haven’t seen it. And then they have this intensive treatment with positive results.”

Researchers have found evidence that girls possess some kind of natural protection against autism that might account for sex differences in how the condition develops because of the need to first overcome this natural protection.

Ventola also believes that the results should encourage researchers and behavioral therapists to treat girls and boys differently.

“I think if we combine boys and girls, we might lose some of our effectiveness,” she said. “We might discount treatment approaches that are just so-so for boys but potentially excellent for girls.”

When you learn something, the brain changes. And we’re overtly changing behavior. We’re teaching them new social skills and seeing the results of this teaching inside the brain itself.

Dr. Pamela Ventola

Ventola’s team didn’t stop there. The study included brain imaging to examine the malfunctioning circuitry that underlies autism and see how it might react to the therapy.

While in a functional magnetic imaging machine (fMRI), the children watched videos depicting points of light that either resembled human motion, such as a stick figure walking, or scrambled motion with no biological similarity. In typically developing children, the lights mimicking biological motion cause blood to flow in the social areas of the brain.

At the beginning of the study, girls with autism showed lower levels of blood flow in these social areas when shown social stimuli compared with boys with autism. Much like with the behavioral results, the girls with autism showed a greater magnitude of change in their neural response than the boys after PRT.

"The brain is plastic,” Ventola said. “When you learn something, the brain changes. And we’re overtly changing behavior. We’re teaching them new social skills and seeing the results of this teaching inside the brain itself.”

An additional aspect of the study explored the impact of the children’s treatment for autism on their mothers, finding a significantly lower level of reported parenting stress after the children completed PRT. There were no significant changes in maternal symptoms of anxiety or depression, though these symptoms were low at the start of the study and did not differ from a sample of mothers of typically developing children.

The study prompted Ventola to partner with Dr. Wendy K. Silverman, Director of the Yale Child Study Center Program for Anxiety Disorders, on a paper comparing differences in parenting behaviors of parents of children with autism and parents of children with anxiety disorders to improve treatment approaches and help support parents. In addition, the project has inspired Ventola to form new interdisciplinary collaborations building on the study’s complex neuroimaging analyses, furthering predictions of treatment responses based on evaluations of sex-based differences found in the neural mechanisms, and advancing the evaluation of sex-based differences in the use of social robotics and eye tracking in autism research.

Ventola has applied for a grant from the National Institutes of Health to expand the study to a larger group of children, hoping to support arguments for strong interventions with girls with autism.

“Girls can be quite impaired, and people may not intervene as strongly because they don’t have as much hope,” she said. “I don’t think that’s the case. I think there is significant hope for these girls even if they start with lower functioning.”

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Submitted by Carissa R Violante on March 31, 2017