Discovery of Pre-symptom Marker of Autism

Researchers use MRI to reveal differences in the brain’s white matter in infants as young as 6 months 

 

While autism’s core behaviors tend to emerge near or after a baby’s first birthday, researchers have long searched for earlier signs. A clear biomarker could lead to earlier therapy that promotes brain development in the crucial first year of life. Identifying early differences in brain biology could also increase understanding of what causes autism spectrum disorder (ASD). In some cases, the biomarker itself might become a target of treatment to prevent or ease debilitating symptoms.

This year, researchers found distinctive differences in brain communication pathways in infants who went on to develop ASD. These differences appeared as early as 6 months and continued through 2 years of age.

The study appeared in the June issue of the American Journal of Psychiatry. It was led by Joseph Piven, M.D. and Jason Wolff, Ph.D., of the Carolina Institute for Developmental Disabilities at the University of North Carolina, Chapel Hill.

As part of their Infant Brain Imaging Study (IBIS), the researchers followed the early brain and behavior development of 92 infants with an older sibling on the autism spectrum. As such, these children were at an elevated risk of ASD, which frequently runs in families.

The researchers used a special type of magnetic resonance imaging (MRI), called diffusion tensor imaging, to record three-dimensional snapshots of brain development at 6, 12 and 24 months of age. In addition, all the toddlers received a behavioral assessment for autism at 24 months. At that time, 28 of the 92 toddlers met criteria for ASD.

As a group, the children who developed autism showed significant differences in white-matter development compared to those who did not. White matter consists of the nerve fibers that connect different regions of the brain. The differences seen in the children who developed autism suggested blunted development of this brain wiring during early infancy in advance of core clinical symptoms.

“A very interesting aspect of the findings was that the brain differences change over time,” Dr. Piven said. “The differences we see at 6 months are not the same as the differences we see at 12 and 24 months. This may help us understand emerging evidence that autistic symptoms unfold or emerge over time.”

In addition, Dr. Piven’s team saw the observed pattern of differences in all 15 white matter tracks they examined in the brain. “This suggests a remarkable convergence of evidence and bolsters our confidence in the finding,” he said.

Previous studies have suggested that autism involves abnormal connectivity between different brain regions. In theory, this could explain the impaired communication and social behaviors that are hallmarks of ASD. For example, a typical infant trying to communicate something of shared interest uses a combination of gestures, babbling and eye contact. This requires several brain regions to communicate with each other simultaneously.

It’s too early to tell whether some form of MRI could be used to identify children at risk for ASD in early infancy, Dr. Piven said. But the results could guide the development of better tools for predicting risk and perhaps for measuring whether an early intervention therapy is improving underlying brain biology.

“The discovery of an early biomarker offers the promise of intervening with treatments before behavioral symptoms become obvious,” said co-author Geraldine Dawson, Ph.D. Dr. Dawson is the chief science officer of Autism Speaks and a professor of psychiatry at the University of North Carolina. “Earlier intervention may increase the likelihood that a therapy can reduce, or perhaps even prevent, the development of autism’s disabling symptoms,” she said. (See related Top Ten story, “Early Intervention Program Changes Brain Activity in Children with Autism.”)

Further research is needed to understand what is causing these differences in early brain development, Drs. Piven and Dawson agreed. This, in turn, could uncover targets for future treatments.

Their study was supported by grants from the National Institutes of Child Health and Development, Autism Speaks, the Simons Foundation, the National Alliance for Medical Image Computing and the National Institute of Biomedical Imaging and Bioengineering. Additional funding from Autism Speaks is enabling the IBIS team to look at genetic and environmental influences on brain and behavior development.

Wolff JJ, Gu H, Gerig G, et al. Differences in white matter fiber tract development present from 6 to 24 months in infants with autism. Am J Psychiatry. 2012; 169: 589-600.

Next: Early Intervention Program Alters Brain Activity in Children with Autism 

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