Courtesy of Yale School of Medicine

Researchers from the Yale School of Medicine will soon be one step closer to unraveling the mysteries of autism, thanks to a new $12.4 million grant from the National Institutes of Health.

The five-year study, jointly funded by the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke, aims to pinpoint early indicators of autism spectrum disorder in fetuses and newborns. Led by Child Study Center professor Katarzyna Chawarska GRD ’00, the project will explore the development of functional brain connections, focusing specifically on families affected by autism.

The interdisciplinary effort involves faculty from the departments of radiology, neuroscience and statistics, including Todd Constable, Laura Ment, Flora Vaccarino, Dustin Scheinost GRD ’13, Fred Volkmar, Suzanne Macari, Kelly Powell, James McPartland and Joseph Chang.

Autism generally manifests in children by the age of two or three years, but the developmental processes that give rise to these symptoms occur during fetal development, Vaccarino said. In this study, the team hopes to use innovative new techniques — such as fetal functional imaging — to see how early signs of autism can be detected in unborn babies, according to Ment.

Chawarska noted that in general, autism is a difficult condition to study and treat because it not only affects multiple areas of function, but also evolves as children grow older. She added that medications currently on the market address only a small fraction of the symptoms, and behavioral interventions typically focus on remediating symptoms rather than addressing the disorder’s underlying mechanisms.

“We’re in a very interesting period right now, in terms of autism research,” Chawarska said. “We know a lot about how it manifests and when it develops, but we still haven’t figured out what causes autism, or what treatments would address the actual mechanism that is responsible for its pathophysiology/physiopathologie and behavioral outcomes.”

Another challenge for autism researchers is that affected patients come from varied genetic backgrounds, and it is unclear which genes or genetic interactions cause the disorder. For this reason, Vaccarino said, this NIH study will focus on analyses within families. Family members share a large part of the same genetic background, so comparing patients with unaffected siblings will decrease variability and allow for a more efficient way of identifying the genetic origins of autism.

Yale scientists have been working with families affected by autism for many decades, Chawarska said. She added that it has also been 10 years since the researchers launched prospective studies of infant siblings of children with autism, a research design that allows for studying precursors and early markers of autism before behavioral symptoms emerge.

“We’ve been able to gain tremendous clinical expertise handling these complex families — both helping them and collecting valuable data,” Chawarska said. “I think we hit a sort of perfect storm when we’re able to bring together expertise from across different domains and create something that is much, much larger than the sum of its elements.”

A benefit of the upcoming collaboration is the ability to examine the disorder from multiple angles, Vaccarino noted. The study includes five interrelated projects, which involve imaging fetuses, newborns and school-aged children, as well as studying induced pluripotent stem cells and behavioral interventions. There will also be four core teams that focus on areas such as statistical analysis and dissemination and outreach.

By combining genetic analysis, neuroimaging and clinical techniques, the team hopes to identify relationships between abnormalities in neurons, brain images and symptoms, Vaccarino said. Collaborations between experts in these different areas is infrequent in the field, so being able to interpret data from the same patients in multiple ways could be “tremendously powerful,” she added.

“I think people recognize that the same old won’t work for autism, and new innovative strategies need to be applied to see how we can help these children,” Ment said.

Taken together, data from molecular biology, neuroimaging and behavioral studies can provide valuable insight into early biomarkers for autism, as well as offer clues about which neural systems are affected during prenatal and early postnatal periods, Chawarska said. With this knowledge, the team hopes to eventually create a new treatment paradigm that can have a larger, more lasting impact on affected children, she added.

Approximately one in 68 children is diagnosed with a form of autism spectrum disorder, according to the Centers for Disease Control and Prevention.


Clarification, Sept. 9: This article has been updated to clarify the difference between the length of time Yale researchers have worked with families versus the studies that focus on infant siblings of children with autism