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A key discussion during research led by Julie Korenberg, a University of Utah neurogeneticist, focused on the relative merits of "Love Me Tender" versus other love songs for evoking an emotional response.

Korenberg's team wound up scratching Elvis from their experiment's playlist after testing their first subject, a woman with Williams Syndrome, who gave no outward response to the King's 1956 classic. But the researchers were really interested in hormonal responses, not overt signs of emotion, and they were in for shock when the data came in.

"It blew us away," said Korenberg, a professor of pediatrics and a member of the U.'s Brain Institute. The woman's blood was flooded with the hormones oxytocin and vasopressin.

"'Love Me Tender' won hands down whether or not they showed anything outwardly," said Korenberg. "It said people can respond emotionally without showing anything on their faces."

More importantly, the data provide strong evidence that people with Williams Syndrome (WS) lack the ability to control levels of oxytocin, a hormone critical to mammalian reproduction and social engagement.

WS is a rare genetic disorder rife with contradictions. People with the disorder have diminished intellectual capacity, yet are very verbal. They are extremely sociable and trusting, yet unable to connect with others. And they have a strong affinity for music.

When Korenberg was at UCLA years ago, she helped identify the string of 25 to 28 genes missing in people with WS, which occurs in about one in 10,000 babies. Korenberg believes these rare individuals can help scientists discover what those missing genes are supposed to do and provide insights into how emotions work.

"We often focus on causes of death — that's what statistics do. But in fact, what we sometimes neglect is that there are many things in our lives that don't kill us, but make us wish we were dead," Korenberg said about debilitating mental health disorders.

Her latest findings, published this month in PLoS One, eventually may help not only WS patients but others with common emotional and behavioral disorders such as autism, depression and post-traumatic stress whose causes are complex and poorly understood, said Korenberg, who moved to Utah in 2008 to lead a newly established USTAR team on brain circuitry.

"This is the tip of the iceberg. We want to make Utah the center of this sort of spiritual and functional behavior research," she said.

For the first time, scientists can be sure that the Williams genetic deletion disrupts regulation of oxytocin, which spurs uterine contractions during birth and the expression of milk. A synthetic form commonly known by the brand name Pitocin is often administered to induce labor.

But oxytocin has many other functions and researchers worry its effects are not well understood. Korenberg's collaborator, C. Sue Carter, calls it "an ancient molecule" that existed long before nature invented uteri and mammaries. Because it is found in mollusks, Carter believes oxytocin was present in life forms that predate the Cambrian moment, when invertebrates and vertebrates parted ways on the evolutionary tree more than half a billion years ago. She suspects it played a role in approach and avoidance among primitive organisms, but now performs a range of poorly understood functions in humans and mammals. Carter is concerned that its synthetic equivalent could be overly prescribed.

"Oxytocin is powerful at a level that we haven't even begun to recognize," said Carter, who conducted ground-breaking research that illustrated the hormone's role in social bonding among prairie voles, which mate for life. She is now a professor of psychiatry at North Carolina' Research Triangle Institute.

In the collaboration with Korenberg, the team recruited 21 people to be evaluated at Cedars-Sinai Medical Center in Los Angeles. Thirteen had WS and the others served as a control group. The Williams cohort had seven women and six men between the ages of 19 and 42. They had triple the baseline oxytocin levels of the control group.

Blood was to be drawn again at five-minute intervals while listening to "Love Me Tender" and afterwards. But after the first subject betrayed little outward response, the team adjusted the experiment's design, instructing the subjects to bring "their favorite music that elicited positive emotions." Some chose to listen to heavy metal.

While the control group registered little or no hormonal changes, the Williams patients consistently exhibited elevated levels.

"Oxytocin is a double-edged sword. Some might say, 'Let's treat everyone with oxytocin. It's the love hormone.' It isn't. Not only is higher oxytocin related to a greater tendency to approach people, but also to less ability to interact," Korenberg said. "We have to be very careful of who we give it to. It touches many regions in the brain."

Lead author on the new study is the U.'s Li Dai, a biochemist with the Center for Integrated Neuroscience and Human Behavior. Others include Ursula Bellugi of the Salk Institute and Hossein Pournajafi-Nazarloo of the University of Illinois. Funding came from the National Institutes of Health.

Williams syndrome

Patients with this rare genetic disorder have trouble understanding spatial and abstract relationships. Despite intellectual deficits, they have dexterity with words and love music. They are extremely social and trusting but lack the ability to sustain relationships. University of Utah neurogeneticist Julie Korenberg studies these patients to shed new light on the circuitry of the human brain. People with WS and their families interested in participating in the research are invited to call KorenĀ­berg's lab at 801-587-0777.