Kerry Ressler hopes his basic science research can help low-income men and women rise above the trauma he's found to be so common among the inner city poor.

Ressler—a physician and a basic scientist—has been shaped by both places, and he's resolved not only to move what he learns from “bench to bedside” but to take it all the way to the violent and chaotic streets where Grady patients live.

“My scientific goal is understanding the biology of fear,” says Ressler, a Harvard-educated M.D./Ph.D. who came to Emory University, in Atlanta, a dozen years ago to train in psychiatry. Now an associate professor of psychiatry and behavioral sciences, he is known for developing rodent models that help reveal what happens in the amygdala—the brain's command center for panic attacks and fight-or-flight responses—when fear is learned, remembered, and sometimes overcome.

Ressler was the lead author on a 2004 article reporting that a drug can boost the effectiveness of exposure therapy that uses virtual reality—a simulated glass elevator—to desensitize patients who have acrophobia, or fear of heights. These findings, which have been replicated in patients with social phobia, panic disorder, and obsessive compulsive disorder, are steps toward what he characterizes as his ultimate “social and political” goal: developing ways to lift weight off poor people who are worn down, held down, and made sick by post-traumatic stress disorder (PTSD) and other trauma-related disorders. But that, he admits, may be a long time coming.

In late 2007, Ressler became the first psychiatrist named an HHMI investigator since Eric Kandel, who was selected in 1984. Kandel went on to win the Nobel Prize in 2000 for insights into learning and memory he acquired by studying Aplysia, a sea slug that looks like a cross between a tree fungus and a football.

“Kerry Ressler strikes me as a role model for the future of psychiatry,” says Kandel, who is director of the Kavli Institute for Brain Science at Columbia University. He laments “disappointingly slow” progress in treating mental health disorders, which he blames on a shortfall of basic science and translational research in psychiatry. A new generation of scientists, he believes, can help close the gaps.

Ressler made his mark in translational research as a second-year resident, shortly after joining the Emory laboratory of renowned amygdala expert Michael Davis. In the almond-shaped amygdala, a structure found deep in the brain, the binding of the excitatory neurotransmitter glutamate to the N-methyl-D-aspartate (NMDA) receptor strengthens synaptic connections when fear is learned or extinguished. Ressler and Davis predicted they could speed the extinction of fear in rats by using an approved human tuberculosis drug, D-cycloserine, which binds and activates the NMDA receptor, thereby increasing glutamate binding in the amygdala. The experiment was a success.

“As soon as we knew it was working, I went to Barbara Rothbaum and asked if we could combine this with psychotherapy in people,” Ressler recalls. Rothbaum is an Emory psychiatry professor who specializes in treating a spectrum of anxiety disorders. They launched a small study comparing the response of acrophobic patients to behavioral exposure therapy with or without a dose of D-cycloserine. Patients given the drug immediately before virtual or real exposure to heights clearly became less fearful than those not given the drug. Before the Emory team published these results in the November 2004 Archives of General Psychiatry, there was nothing in the literature about pharmacologic enhancement of fear extinction.

Photo: Gregory Miller

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