To unravel autism’s mysteries, one neuroscientist looks at the developing brain

WASHINGTON — As the number of children diagnosed with autism spectrum disorder increases, so too has research on the complex and poorly understood disorder. With powerful genetic tools, advanced brain-imaging methods and large groups of children to study, the field is poised to make big contributions in understanding — and potentially treating — autism.

Neuroscientist Kevin Pelphrey, who is formerly of George Washington University in Washington, D.C., but has recently moved to the University of Virginia in Charlottesville, studies autism’s beginnings. He described some of his findings about the link between brain development and the disorder on October 15 at a meeting of the Council for the Advancement of Science Writing.

Here are some of the key points Pelphrey made on how autism may get its start in the developing brain, how the disorder is different between boys and girls, and how large, long-term studies of children with autism might yield clues about the condition.  

What causes autism spectrum disorder?

For most cases, no one knows. There’s likely no single cause — environmental and genetic risk factors work in combination. In some children, rare mutations in key genes have been linked to the disorder. More commonly, many genetic changes, each with a small influence on overall risk, may increase a child’s likelihood of developing the disorder.

With the number of autism diagnoses growing, partly due to better detection, researchers are looking at potential factors beyond genetics, such as parents’ age, premature birth and maternal obesity.

When does the disorder begin? 

On average, kids are diagnosed with autism around the age of 4, though symptoms can appear by around age 2. But Pelphrey says the disorder starts long before then, as the brain is built in utero (SN: 4/29/17, p. 10). Evidence is growing that alterations in brain development, perhaps in nerve cell connections or communication between brain regions, are involved in the disorder.

By studying newborns and even fetuses, Pelphrey aims to uncover some of the key differences in the brains of babies who go on to develop the disorder. That early detection could ultimately allow clinicians to change the brain’s developmental trajectory in a way that prevents the disorder.

How close are scientists to an autism biomarker?

Biological signatures, or biomarkers, of autism might enable both earlier detection and a way to see if interventions to treat the disorder are working. In 2017, researchers found signatures of autism in the brains of 6-month-old babies who would go on to be diagnosed with the disorder at age 2. Other attempts to find autism markers involve abnormal neural activity, differences in eye contact and even changes in gut microbes.

But for a biomarker to be useful, it needs to check a lot of boxes, Pelphrey said. It must be reliable, predictive, informative at the individual level and easy to bring into pediatricians’ offices, among other things. So far, none of the proposed biomarkers check all of those boxes.

Along with colleagues, Pelphrey is studying the utility of a brain-imaging technique that could make spotting abnormal neural activity a little easier for clinicians. Called functional near-infrared spectroscopy, it uses light to measure oxygenated blood as a proxy of brain activity. The method is less precise than MRI but cheaper and more mobile.

Why do more boys get autism diagnoses than girls?  

Researchers don’t yet know for sure. Scientists recently began studying the differences between boys and girls, in the hopes of explaining why an estimated four boys are diagnosed with autism for every girl diagnosed. One clue comes from big genetic studies that suggest girls are somehow more resistant to genetic mutations than boys (SN Online: 2/27/14). Sex hormones may also have something to do with the differences between boys and girls, Pelphrey says.

What’s more, by looking at brain behavior, scientists are beginning to suspect that girls’ autism is, at its core, distinct from that of boys. “The behaviors that we call autism, while on the surface are the same, have different biological origins,” Pelphrey says.

Females with autism, for example, are more likely to have stronger social abilities, though it may be hard work for the girls, a 2017 study suggests.

What’s the future of autism research?

Autism is an idiosyncratic disorder, one that’s likely a bit different for each person. As such, making progress toward understanding common pathways will require large numbers of subjects and many types of measurements.

With collaborators, Pelphrey has collected data on genetics, brain behavior and structure, and behavior for about 500 children with autism, about half of whom are girls, he says. That project will continue to recruit more participants and also collect personal experiences and adult outcomes.

Other large research collectives will likely move the field forward, such as the Simons Foundation’s Simons Simplex Collection, which contains genetic samples from 2,600 families with children with autism.