Brain scans can reveal innovative biomarkers for developmental disabilities like autism, Angelman syndrome, and Down syndrome, as well as the potential impact of environmental factors, according to Mark Shen, Ph.D., from the University of North Carolina at Chapel Hill (UNC-Chapel Hill). Shen gave the special guest lecture on April 20 at NIEHS in honor of World Autism Month.

“These findings can suggest new ways to identify infants who may benefit from early services, supports, and interventions,” said Cindy Lawler, Ph.D., who hosted the event with Astrid Haugen both from the NIEHS Genes, Environment, and Health Branch.

Shen leads the Lab for Developmental & Clinical Neuroscience at UNC and is on the executive committee of the Infant Brain Imaging Study (IBIS) Network, one of 10 NIH-funded Autism Centers of Excellence. Before doing research, he worked for six years doing clinical work in the community as a behavioral therapist with children with autism.

Earlier detection

Autism, also known as autism spectrum disorder (ASD), is a broad range of conditions affecting the way people communicate, behave, or interact with others. Once considered rare, the Centers for Disease Control and Prevention now estimates that the disorder affects about 1 in 36 children in the United States.

Typically, children are diagnosed with ASD around three or four years of age, based on their developmental history and certain behaviors like avoiding eye contact or repeating words or phrases. Several studies have shown that early detection improves outcomes for children on the spectrum.

“Behavior symptoms that are diagnostic for autism aren’t usually evident until one or two years of age, but brain changes have been identified in the first year of life,” Shen said.

Altered early brain development

Using magnetic resonance imaging (MRI) scans and clinical assessments with 400 infants, and then studying the underlying biology with animal models, Shen and colleagues are working to identify biomarkers that could help detect ASD earlier.

They have found that a part of the brain called the amygdala, which is associated with processing emotions, begins an accelerated growth between 6-12 months of age in children who later developed autism.

His team also found that babies who later develop autism have too much cerebrospinal fluid surrounding their brains as early as 6 months of age. Such fluid cleans the brain of neural waste products, which should be efficiently cleared from the brain throughout the day. Cerebrospinal fluid also filters out inflammatory proteins secreted by neurons, including beta amyloid and Tau, which if they accumulate are known to be harmful to the brain.

Environmental impact

A next step in this research is to understand if poor cerebrospinal fluid circulation affects the brain’s ability to filter out potential environmental exposures. Shen is collaborating with NIEHS grantee Heather Volk, Ph.D., from Johns Hopkins Bloomberg School of Public Health to understand the link between brain imaging markers in autism and prenatal exposure to air pollution. They are also assessing other biomarkers by gathering shed baby teeth to analyze exposures to toxic metals.

“These kinds of collaborations, which bring together environmental health scientists with scientists with deep expertise in autism, are essential to develop a full understanding of complex disorders such as autism,” said Lawler.

Beyond autism

Shen and colleagues are currently conducting additional studies comparing brain scans of autism with other neurodevelopmental disabilities, including Angelman syndrome, fragile X syndrome, and Down syndrome. There is surprisingly little known about the brain development of these conditions in the first year of life. It is important to tease apart the similarities and differences in brain growth of these children to develop more individualized and specific therapeutics for each condition.

Shen’s research suggests that it is very possible to identify early biomarkers using MRI scans.

“We’re encouraged by this because we want to do research that can ultimately improve the quality of life of those with developmental disabilities,” Shen said.