The Biology Behind Autism Spectrum Disorder

One in 44 children living in the United States is diagnosed with autistic spectrum disorder (ASD) —a condition that can present with a diverse range of challenges, especially relating to social communication. While ASD is well-studied, scientists’ knowledge of the biology behind the disorder is still limited.

To improve the scientific basis for understanding ASD, James McPartland, PhD, professor in the Yale Child Study Center and director of the Yale Developmental Disabilities Clinic, is studying the biomarkers associated with the condition—biological characteristics that can be objectively measured. McPartland spoke about the advances his lab has made during his grand rounds presentation, “Progress in Biomarker Development in Autism Spectrum Disorder” on November 9.

“Right now, every decision we make about how to help autistic individuals is based on our subjective clinical thinking,” he says. “We’re trying to create biologically-based tools that can help with clinical research and practice in autism.” Autistic people often have difficulty with interacting socially with others, and may show restricted interests, repetitive behaviors, or unusual responses to sensory information. They can also have a diverse range of experiences. While many individuals and their families struggle with the obstacles ASD can present, the rising neurodiversity movement has also shed light on the manner in which many others feel ASD has advantages as well.

McPartland’s interest in ASD research stems from a collegiate internship he had as an assistant teacher for children with disabilities. He says he felt especially “captivated” by his students with ASD. “I was fascinated by what it meant about the brain—that a child could be so skilled in some areas, but not be comfortable with what most do unthinkingly, like making eye contact or having a conversation,” he says.

McPartland’s research focuses on innovating new biomarkers, or in other words, developing new ways to quantify the biology associated with ASD. From the beginning of his research career, for example, he has been looking at how the brains of autistic people respond to faces. Using an electrocephalogram (EEG), in which a soft, noninvasive net containing small electrodes is placed over the head of the subject, his lab measures electrical brain activity associated with facial recognition. This electrophysiological response occurs at around 170 milliseconds in neurotypical individuals. In autistic people, on the other hand, his lab found that the response is delayed.

However, research on autism biomarkers poses challenges for scientists. While experts have identified many promising biomarkers, studies on potential candidates have limited reproducibility. McPartland’s finding on N170 latency in autistic individuals is one of the most well-replicated neuroscience findings in autism, but has not been detected in all samples. “What we call autism is just a behavioral convergence of a number of contributing pathways. To try and pin down the biology in any one specific domain is hard,” McPartland says. “We have many candidate biomarkers, but we don’t have a deep understanding for how they can be used and for whom they can be used.”

These challenges highlight the need for more rigorous biomarker research. As a result, McPartland leads the Autism Biomarkers Consortium for Clinical Trials (ABC-CT), a multicenter study based at Yale. The first phase enrolled 280 autistic children and 119 neurotypical children and looked at four EEG biomarkers and five eye tracking-based biomarkers. The study utilized unprecedented methodological rigor—even ensuring the lighting and temperature were exactly the same at each site—to eliminate as much noise as possible.

The US Food and Drug Administration (FDA) recently introduced a biomarker qualification program to quantify and validate biomarkers supported by strong scientific evidence. As a result of the ABC-CT trial, N170 latency became the first biomarker for any psychiatric condition to be accepted into the program. A second eye tracking-based biomarker was also accepted shortly afterwards. “Our hope is not necessarily to use these biomarkers as diagnostic tools, but rather use them in terms of defining autism subgroups,” McPartland says.

McPartland’s team launched phase two of ABC-CT in May to expand on their findings from the first study. The second phase will bring back the children from the original cohort to observe how biomarkers may change over time, and also bring in an independent sample of 400 children to try and replicate the findings of the initial study.

There are currently no clinical decision-making tools based in biology for helping autistic individuals. And while there are medications available to treat symptoms of autism like anxiety or repetitive behaviors, no medical treatments are available to help people struggling with autism’s core features. Through creating these tools, McPartland hopes to encourage a wider range of groups such as device manufacturers or pharmaceutical companies to become more involved in autism treatment. “It is an impediment to not have biomarkers because it is a disincentive for businesses to invest without quantitative markers,” he says. “Considering how prevalent autism is in the world, the amount of investment is really low.”

Many autistic people also struggle with co-existing conditions such as depression or anxiety. Therefore, says McPartland, individuals who are comfortable with their autism may also benefit from his work. “It’s important to me for people to understand that greater knowledge of biomarkers in autism is entirely concordant with the neurodiversity movement,” he says.

Depression’s relationship with autism biomarkers is the subject of research by McPartland that goes beyond ABC-CT. Other research involves trying to use biomarkers to develop new treatments. Transcranial magnetic stimulation, for example, is an FDA-approved treatment for depression, but its applicability in autism is not yet understood. McPartland is also especially excited about studying biomarkers in autistic children who also have significant intellectual disability, a group that has been historically excluded from autism research.

For more information about the research conducted in McPartland’s lab and opportunities to participate in research, families are invited to visit the McPartland lab website.