WASHINGTON—At a time when US troops in Iraq and Afghanistan are being diagnosed with traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD), a panel of researchers explored factors that might confer either heightened resilience to or heightened risk for PTSD. The informal panel discussion was sponsored here last month by the Dana Alliance for Brain Initiatives in Washington, DC.
RESILIENCE TO PTSD
Dennis Charney, MD, dean of the Mount Sinai School of Medicine, said he started studying PTSD in Vietnam veterans in 1980. About 20 to 30 percent of Vietnam veterans (more than 1 million) have been diagnosed with PTSD, according to statistics from the NINDS.
“We became interested in why some people did not develop PTSD from trauma,” said Dr. Charney, who is also a professor of psychiatry, neuroscience, pharmacology, and systems therapeutics.
In studies of veterans from the Special Forces and Navy Seals and former prisoners of war (POWs), resilient people generally fell into three categories: they had no symptoms following trauma; they had symptoms — flashbacks, sleep disturbance, anxiety, irritability, and an exaggerated startle response but recovered; and they had the same symptoms but forged ahead living their lives despite the symptoms.
Dr. Charney, a former mood and anxiety disorders researcher at the National Institute of Mental Health (NIMH), said those with resilience to PTSD developed coping mechanisms under pressure. He cited the case of a POW who built a house in his mind, “nail by nail, cabinet by cabinet, room by room.”
“When he got out he built it,” Dr. Charney said. Other POWs, he said, wrote novels in their heads while confined, and published them when they were released.
Dr. Charney theorized that in those with PTSD the amygdala is activated too readily, and is not suppressed in a normal way by the prefrontal cortex — as shown on functional MRI. In PTSD-resilient people, however, the prefrontal cortex has robust suppression, he said.
“Early life experiences that are out of the comfort zone” help people develop techniques that lead to resilience, added Dr. Charney. “You're born with the fear circuitry because you need it to survive,” he said. “Experience modulates the circuitry.” Thus a scrappy childhood can lead to the development of coping strategies that can be called upon when needed.
Dr. Charney said army basic training now includes exposing soldiers to traumatic experiences to help them develop coping mechanisms; mock POW camps are an example. In addition, said Dr. Charney, there is undoubtedly a genetic influence on resilience — “resilient people do seem to have a biologic optimism that they were born with.”
TBI: BRAIN DIFFERENCES
Structurally, where a TBI occurred in the brain can reduce the likelihood of subsequent PTSD, said Jordan Grafman, PhD, senior investigator in the Cognitive Neuroscience Section at NINDS. In examining the records of veterans in the Vietnam Head Injury Study — whose brain injuries were mapped with CT — Dr. Grafman and his colleagues found that if a TBI occurred in the amygdala or the ventromedial prefrontal cortex, PTSD was less likely to develop than when the TBI occurred in other parts of the brain. The study appeared in the December 2007 Nature Neuroscience.
“In people with amygdala damage, not one developed PTSD,” said Dr. Grafman. [See Neurology Today's “Damaged Brain Regions Protect Against PTSD,” Feb. 21, 2008, on www.neurotodayonline.com.]
“One of the big questions is how to disentangle what the person's main problem is,” he said. “The presentation is often difficult.”
Ideally, said Dr. Grafman, it would be advantageous if the military could identify people who are less likely to recover from a TBI — through use of a risk profile. “It really is sort of a business issue for the military,” he said, because the risk profile could help to determine when the soldier could be re-deployed and under what kinds of work conditions.
PTSD: ‘A DISEASE OF MEMORY’
Steven Hyman, MD, provost of Harvard University and a former NIMH director, cautioned that there are people with TBI whose injury does not show up on CT or MRI. What is known is that vulnerability to PTSD can be caused by heightened memory, he said.
“We have structures in the brain that learn about dangerous situations very well,” he added. “In some ways PTSD is almost a disease of memory. The memories are just suppressed; they're not erased…Memories encoded under strong emotion really stick with us.”
Dr. Hyman said emerging findings from neuroscience research may enable better treatment of PTSD, whose standard treatments of antidepressants and cognitive behavioral therapy (CBT) he called “not adequate.”
“It's likely that PTSD is more like hypertension, where there's no bright line that separates the well from the not well,” Dr. Hyman said. “The good news is that if you know what parts of the brain are affected, we can say, ‘What are the molecules we might apply new treatments to?’”
Since it is known that the prefrontal cortex exerts cognitive control over the fear response and that CBT can help the patient exert that control, it should be possible to develop better treatments for PTSD, he said.
Dr. Hyman noted that if the neurobiology of fear memories could be elucidated, it might be possible to develop a drug for soldiers exposed to trauma in combat to prevent debilitating PTSD. “This would be much more successful than beta blockers,” he said. But, he cautioned, such a pill should not be abused for painful memories in normal life such as the breakup of a romance. “If you try to dampen any memory that has a sting to it, that could have dire consequences,” he said.
Dr. Charney, whose current research includes a focus on intranasal ketamine for treatment-resistant depression, agreed that better testing is needed to define both TBI and PTSD. “I think our field has not shown the discipline with our imaging tests such that they are standardized from one lab to another,” he said. “In other branches of medicine, diagnostic tests are standardized.”
As for new treatments for PTSD that tap into the fear circuit, Dr. Charney said: “The pharmaceutical companies when left to their own devices go after diseases that make them the most money, and PTSD isn't one of them.”