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Autism Risk Gene Linked to Sensory Overload

February 02, 2012

New research may help explain how a specific gene mutation produces the hypersensitivities to sound experienced by many persons affected by autism spectrum disorder (ASD).

The researchers found that when a suspected autism gene – PTEN – is disabled in the sound-processing center of a mouse brain, incoming signals are abnormally amplified regardless of whether their source is near or far.

"It's long been hypothesized that autism spectrum disorders (ASDs) arise from a partial disruption of long-range connections in the brain during development,” explains study leader Anthony Zador, M.D., Ph.D., a neuroscientist with the Cold Spring Harbor Laboratory, in New York. "Our finding that PTEN-deficient neurons receive stronger inputs suggests that one way this disruption can be caused is by signal enhancement." The study – funded by Autism Speaks and the National Institutes of Health – appears in the Journal of Neuroscience.

“This is an exciting study that offers insight into why some people with autism suffer auditory hypersensitivity,” comments Autism Speaks Chief Science Officer Geri Dawson, Ph.D. “As we discover the biological basis of this common symptom, we come close to developing effective treatments that can help those who struggle with it.”

Although ASDs can arise from mutations in any of dozens of candidate genes, hypersensitivity to sound is a common symptom. The brain’s hearing center, or auditory cortex, plays a critical role in attention and perception to sound and language. It also connects with other critical brain areas, including those that process other types of sensory information. For this reason, the auditory cortex has been a target of research aimed at understanding how changes in brain circuits contribute to the symptoms of ASD.

PTEN mutations have been found in individuals with both autism and extreme macroencephaly, or increased brain volume. Previous studies have found that PTEN loss in animal models boosts brain cell size and interconnections between brain cells.

Using adult mice, Zador's group disabled the PTEN gene in select parts of the auditory cortex, while leaving the gene intact in neighboring brain cells. They then assessed the effect by stimulating brain cell activity in the auditory cortex. This resulted in abnormally strong sensory signals regardless of whether the incoming stimuli came from a local or distant source.

However, these effects could be blocked by treating the PTEN-deficient mice with rapamycin, a powerful immune-system suppressant most commonly prescribed to prevent organ rejection. In examining the animal’s brain tissues, the researchers found that the drug prevented the abnormal increase in cell interconnections otherwise seen in PTEN-deficient mice (image above).

“While this study is exciting, we need to know more before it would be appropriate to use rapamycin as a treatment for individuals with autism,” adds Joe Horrigan, M.D., Autism Speaks head of medical research.  “Safety considerations are of paramount importance as rapamycin can increase susceptibility to infections and malignancies such as lymphoma. At present, it should be prescribed only by physicians experienced in immunosuppressive therapy.”

For a personal take on this study, please see the related blog post by "Free Range Aspergian" John Elder Robison. You can also explore this and other studies Autism Speaks is funding using our grant search.