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Larry Young on animals and autism clues, environmental impact on hormone brain function

July 20, 2005

APS meeting highlights shift toward oxytocin and vasopressin in human social behavior

STEAMBOAT SPRINGS, Colorado - As animal models go, the vole isn't near the top of the list. In fact, it wasn't even on the list until relatively recently. Not to be confused with the mole, a much smaller and scientifically less-interesting rodent, voles are about the size of hamsters, but more squat.

Nevertheless, along with their cousins the mouse and rat, voles have quickly become an invaluable animal model for social behavior and have helped open up the field of study to very complex issues including romance and even more recently, autism.

Larry Young, professor of psychiatry at Emory University, began studying the vole in the mid-1990s "unrelated to autism, just for their unusual behavior. Prairie voles are monogamous and form life-long social attachments, while montane and meadow voles are promiscuous breeders and don't form social attachments at all," Young says. Soon, "using comparative molecular approaches, I began to investigate the molecular mechanisms underlying the species behavior differences. Now, by gaining an understanding of the mechanisms underlying social attachment, we hope to gain insight in human disorders characterized with social impairments, such as autism."

But to paraphrase Michael Douglas in the "American President": "Autism isn't easy." Young says there are two specific problems in studying autism. First, "there aren't any animal models of autism. Animals just don't get autism. Second, autism is itself a disrupted social phenotype with a broad spectrum of interrelated disorders" that is almost uniquely variable in each individual patient.

Editors note: Larry Young is the closing keynote speaker at the American Physiological Society's 2005 Conference, "Neurohypophyseal Hormones: From Genomics and Physiology to Disease," and the latest developments toward clinical applications, July 16-20 in Steamboat Springs, Colorado.

Environmental impact on OT/VP in brain function

Indeed, Young said that the "exciting trend reflected at this conference is the new research emphasis on the role of oxytocin (OT) and vasopressin (VP) in modulating social behavior. This is exciting because OT was the first peptide to be chemically identified, followed closely by VP. They are both known to be critical for survival and reproduction and in their 'peripheral' functions they are very highly conserved and consistent among many species," Young noted.

"But it turns out that the social behavior receptors in the brain are very plastic, and they're located in different places. These receptors can be shaped not only by genetics, but by each individual's own experience, which then impacts how they act toward their offspring. These differences are very interesting from both evolutionary and developmental viewpoints," Young added.

Opening the door on autism

Based on earlier work by Thomas Insel and Sue Carter on voles, Young's laboratory has focused on OT, VP and the brain's reward system. His studies "demonstrate that vole species differences in OT receptor and VP1a receptor (VP1aR) expression patterns in the brain likely underlie species differences in social organization."

He noted that OT knockout mouse studies confirm the role of OT and VP in social cognition and suggest a developmental role for OT in shaping normal adult social behavior.

"These observations have important implications for psychiatric disorders characterized by disruptions in social cognition and reciprocity, such as autism. Several autism studies are consistent with a role for OT and VP in this devastating disease of the social brain," Young noted. "These studies include altered processing and decreased plasma OT in autistic children, and linkage disequilibrium between the VP1aR microsatellite and autism. Thus animal and clinical studies suggest that disregulation of OT and VP systems could potentially contribute to the disrupted social phenotype found in autism spectrum disorder," he said.

However, Young cautioned, more studies need to be conducted to confirm a role for these peptides in autism. "If you study the normal neurobiology of social behavior, you can gain insights into specific brain mechanisms that may be disrupted in autism. But there are other deficits, and so I'm sure autism is a complex neural development disease. But you have to focus on one of the 'deficits' at a time. For social behavior, we had to see what neural chemicals and genes are involved," Young explained.

Young said the important contributions in autism research by voles, mice, rats and sheep shows that "scientists must look in nature for the variability of behavior and physiological systems that might be applicable to human conditions. In this instance," Young added, "we wouldn't have looked at the VP1AR gene in relation to autism, but because we were following its role in social attachment behavior we came to a very useful hypothesis."

American Physiological Society