Study Provides Evidence Associating Autism with Defects in Myelin

Study Provides Evidence Associating Autism with Defects in Myelin

It’s still unclear what’s different in the brains of people with autism spectrum disorders, but evidence from genetic and cell studies points to abnormalities in how brain cells (neurons) connect to each other. A study now provides visual evidence associating autism with a disorganized structure of brain connections, as well as defects in myelin — the fatty, insulating coating that helps nerve fibers conduct signals and that makes up the brain’s white matter.

Researchers used advanced magnetic resonance imaging (MRI) to image the brains of 40 patients (infants to age 25) with tuberous sclerosis complex and 29 age-matched, healthy controls. Tuberous sclerosis is a rare genetic condition often associated with cognitive and behavioral deficits, including autism spectrum disorders about 50 percent of the time.

“Patients with tuberous sclerosis can be diagnosed at birth or potentially before birth, because of cardiac tumors that are visible on ultrasound, giving us the opportunity to understand the circuitry of the brain at an early age,” explains researcher Mustafa Sahin. “Our ultimate goal is to use imaging in infancy to find which tuberous sclerosis patients are at high risk for autism so we can intervene early. This may have implications for autism in patients without tuberous sclerosis as well.”

The team used a relatively new MRI technique called Diffusion Tensor Imaging to trace the pathways of nerve fibers by measuring the diffusion of water in the brain. In the January issue of the journal Academic Radiology, they report findings in the corpus callosum, the brain’s largest white-matter structure that acts as a highway transferring signals between the left and right cerebral hemispheres.

Of the 40 patients with tuberous sclerosis, 24 had clinically significant developmental delays or intellectual disability, and 12 had autism spectrum disorders. Autism spectrum disorders were diagnosed clinically by a pediatric neurologist, and, in most cases, by the Autism Diagnostic Observation Schedule (ADOS).

In general, compared with controls, patients with tuberous sclerosis had higher radial diffusivity values, a measure of water diffusion out of (perpendicular to) the nerve fibers (axons). Radial diffusivity is an indirect measure of how well insulated the axons are: Having higher radial diffusivity means axons are poorly insulated with myelin, suggesting abnormalities in the white matter (which is partly made up of myelin.

Patients with both tuberous sclerosis and autism spectrum disorders not only had increased radial diffusivity — compared with both non- autism spectrum disorder patients and controls — but they also had clearly disorganized axon pathways.

“This study shows that we can use diffusion tensor imaging to differentiate tuberous patients with autism from those without autism,” says Sahin.

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