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Research May Help Enhance Social Cognition in People with Autism

August 2008 - The Centers for Disease Control estimates that 1-in-150 children nationwide are diagnosed with autism spectrum disorder (ASD), making it more common than pediatric cancer, diabetes, and AIDS combined. These statistics have led some to refer to the behavioral disorder as an “urgent public health concern.”

ASD is a developmental disorder characterized by aberrant social interactions, impairments in communication and repetitive stereotyped patterns of behavior. CBN student Meera Modi is conducting research that may lead to a potential treatment that could enhance social cognition and ameliorate some of the social deficits in ASD.

Modi is a rising fourth-year Emory University Neuroscience Graduate Program student who works in the lab of Larry Young, Ph.D., Professor in the Department of Psychiatry and Behavioral Sciences at Emory University’s School of Medicine and the Yerkes National Primate Research Center.

Previous CBN-supported research in Dr. Young’s lab found that mice lacking oxytocin fail to process social cues normally and that oxytocin receptors in the brains of monogamous prairie voles promote social bonding. Based on these results, it has been suggested that inadequate levels of oxytocin, possibly in the amygdala might explain the inability of autistic people to recognize social cues and to create normal social relationships.

“I am working to develop social bonding in the prairie vole as a predictive model for the development of drugs that may be useful in enhancing social cognition in individuals with autism,” Modi said. “Prairie voles have a much more complex repertoire of social behavior than either rats or mice, and social bonding in voles relies on a series of social cognitive processes. By studying an animal with complex social behavior we are better able to characterize specific phenotypes, look at the neurobiological mechanisms underlying them and determine how different pharmacological agents may affect them.”

As a part of an Autism Speaks Fellowship she received in December 2007, Modi will conduct a series of experiments designed to understand the interaction between oxytocin and glutamate, which includes testing whether clinically available glutamatergic compounds can enhance social cognition in the prairie vole.

“Both oxytocin and drugs that target the glutamate system are currently under investigation as possible therapeutic agents in autism so our studies are important to clarify how they may be operating in the brain,” she said.

Modi’s interest in the effects of glutamate receptor agonists led her to D-cycloserine (DCS), a drug formerly used to treat tuberculosis. CBN-supported research led by Mike Davis, Ph.D., and Kerry Ressler, Ph.D., of Emory University’s School of Medicine found that DCS, an NMDA receptor mixed agonist that enhances synaptic transmission in the amygdala and other parts of the brain, enhances the extinction of conditioned fear in rats and some socialphobias in humans.

Inspired by the work of Drs. Davis and Ressler, Modi and Dr. Young found that giving DCS to female prairie voles promotes partner preference formation in female prairie voles under conditions in which social bonds do not typically form, suggesting that it enhances some aspects of social cognition.

“This is the first study to show that modulation of the glutamate system can enhance social bonding,” Modi said. “We hypothesize that by enhancingglutatergic transmission in the nucleus accumbens, we are expediating the process of social learning, such that the application of DCS promotes the long term encoding of the rewards associated with social interaction. The drug has already been approved for use in humans, allowing our tests in voles to have direct implications for humans.”

Further studies will explore the effect of a combination oxytocin and DCS therapy on the enhancement of social bonding in voles and as a therapeutic strategy to treat the social cognitive deficits in ASD.

Photo courtesy of Larry Young, Ph.D., Emory University

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