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University of Wisconsin Monkey Study Looks at Hard-Wiring of Anxiety in Childhood

July 14, 2008

MILWAUKEE _ Anxious individuals may be hard-wired in childhood to be tense, nervous and prone to depression, new research suggests.

University of Wisconsin-Madison researchers have discovered the part of the brain linked to anxiety in young monkeys, a finding that could help our understanding of the neural basis of temperament in human children as well.

“They were able to link behavioral traits related to anxiety with strong and stable activity of a central circuit of brain area,” said Alessandro Bartolomucci, a psychobiologist at the University of Parma in Italy, who was not involved in the research.

The central core of the brain’s anxiety center was found in the amygdala, a part of the brain that controls emotional reactions, such as the fight or flight response.

Antsy monkeys with high amygdala activity also had greater levels of the stress hormone cortisol in both safe and threatening environments.

“The circuit in the brain is predictive of how anxious and how high levels of stress hormones are in the monkey,” said University of Wisconsin-Madison psychiatry professor Ned Kalin.

“If you take a young monkey and put it in a situation that is uncertain or a little scary, the animals that have the greatest activity in the amygdala are the ones that appear to be the most anxious.”

Kalin, together with his graduate student Andrew Fox, measured brain activity, cortisol levels and behavioral traits in adolescent rhesus macaques, which have long been used as a model to understand anxious temperament in human children.

The researchers injected a radioactive dye and tracked the monkeys’ brain activities in a number of situations ranging from being at home with cage-mates to being alone in a novel environment to being confronted by an unfamiliar person.

Whether in a secure or threatening situation, the most nervous monkeys had greatest activity in the amygdala and surrounding stress-response brain regions. They also tended to stand still and stay quiet for prolonged periods, and release more cortisol.

“Individuals that have a predisposition (to anxiety) have a brain circuit that is always on; it doesn’t turn off like in normal individuals,” said Kalin, who published his findings this month in the journal Public Library of Science ONE.

These signature anxiety-related traits _ collectively termed “behavioral inhibition” _ are analogous to children who hide behind their parents’ legs, fail to smile or are otherwise extremely timid in unfamiliar situations.

Many studies have shown that behaviorally inhibited children are significantly more likely to develop social anxiety disorders in later life. These new findings in young monkeys point to the brain mechanisms that predispose children to mental illness.

“This is fairly extreme behavior, but it’s not abnormal in and of itself,” Fox said. “But as an animal continues to do it over a 30-minute period, it’s no longer getting any utility from it.”

The study “really adds to the theoretical knowledge,” said Maaike Kempes, a behavioral biologist at Utrecht University in the Netherlands who was not involved in the study. “People may have thought of this beforehand, but showing it is really important.”

She noted, however, that the monkeys were reared in pairs, rather than with their mothers and multiple peers, as they would be in nature, and this could affect their brain development.

“They’re not socially housed, and that really affects their behavior and how their brains are shaped,” she said.

Bartolomucci also noted that whether male and female brains are wired differently remains unanswered. The study showed minor gender differences, with females more anxiety-prone than males, although the effect was not statistically significant.

“It seems like there might be a small gender trend that would be compatible with what we know in humans,” Fox said. “It’s intriguing to think that the (gender) difference is a biological difference rather than a societal difference.”

By pinpointing the anxiety center of the brain, the study establishes the monkey model as a foundation for understanding the neural development of human disorders.

“What the monkey data really allows us to do is to start and look at different treatments that we might speculate would be helpful for children,” said Fox. “I’m pretty confident this is something we can start to extend to humans.”

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