July 27, 2008 -At a recent conference for some of the area’s leading neurologists, San Francisco physicist Norbert Schuff captured his colleagues’ attention when he presented colorful brain images of U.S. soldiers who had returned from Iraq and Afghanistan and were diagnosed with post-traumatic stress disorder.
The yellow areas, Schuff explained during his presentation at the city’s Veterans Affairs Medical Center, showed where the hippocampus, which plays major roles in short-term memory and emotions, had atrophied. The red swatches marked hyperfusion – increased blood flow – in the prefrontal cortex, the region responsible for conflict resolution and decision-making. Compared with a soldier without the affliction, the PTSD brain had lost 5 to 10 percent of its gray matter volume, indicating yet more neuron damage.
Schuff, who was dressed in a Hawaiian shirt just as colorful as the brain images he’d brought, reminded his colleagues that while his findings were preliminary and the trials ongoing, researchers were at least inching closer to finding the biological markers that distinguish a brain affected by PTSD. As the technology of brain imaging improves and the resulting data are refined, doctors believe that one day they will be able to look at a computer screen and see PTSD as clearly as they now see a brain tumor.
“But we’re still in the infancy of neuroimaging,” Schuff cautioned later in his office. “Do you get PTSD because you have a small hippocampus? Or does a small hippocampus mean you’ll develop PTSD? That, we still don’t know.”
Schuff’s research is at the forefront of a bold push by the Department of Defense to address PTSD, the psychological disorder that will haunt an estimated 30 percent of the veterans returning from the current two wars, according to the Pentagon. Forty thousand veterans from Iraq and Afghanistan, Pentagon officials say, have already been diagnosed with PTSD, which is defined as an anxiety disorder triggered by exposure to traumatic events; symptoms can include nightmares, flashbacks and panic attacks.
Left untreated, clinicians say, patients with PTSD are more likely to engage in anti-social behaviors such as alcohol and drug abuse. The disorder, neurologists are now learning, can also lead to long-term maladies, such as Alzheimer’s and dementia.
Manhattan Project urgency
The quest is to understand how the disorder begins inside the brain. The Defense Department has invested $78 million in San Francisco’s Northern California Institute for Research and Education at the VA center in the past four years, making it the largest VA research institute in the country and the only one that specializes in neuroscience. With 200 researchers on staff, and an estimated 40 ongoing studies that rely on 60 to 80 veterans as research participants, the center has the urgency of a Manhattan Project site, this time searching for a way to end a mental health crisis.
The Department of Defense “has such a compelling need for these answers,” said Dr. Thomas Neylan, an associate professor of psychiatry at UCSF and director of the post-traumatic stress disorder program at the VA center. “They want to know these answers now, which is the right approach. We want the answers now; people are still going off to the war, coming back, and a lot of them are suffering for a long time.”
The search for PTSD biological markers through brain imagining is the primary concern of five research centers in the country, including teams at Harvard and Emory universities. Researchers believe that once the markers are defined, successful treatments can be developed.
Since 1995, magnetic resonance imaging, or MRI, has been used to explore the brain through mostly black-and-white images with fuzzy resolution. But in the past few years, advances in computer-imaging technology have enabled neurologists to detect the smallest changes in brain activity.
At the San Francisco VA center, thanks to the installment five years ago of a $4 million MRI machine called the 4T – T stands for Tesla, a unit of magnetic field – Schuff and his colleagues are now able to look into the brain at 1 millimeter resolution, in color and in 3-D. By contrast, Schuff said a 1.5T MRI machine could not register atrophy on PTSD brains. But the 7T MRI machine that was installed at the UCSF Mission Bay campus last year can detect microscopic neuron damage that a 4T is incapable of “seeing.”
“With each stronger magnet, we get a finer view of what’s going on in the brain,” Neylan said.
These advances allow neurologists not only to further understand PTSD, but to study its relationship with brain trauma, one of the leading injuries incurred by soldiers in the Iraq and Afghanistan wars.
The effects of IEDs
At the VA conference, titled “The Brain at War: Neurocognitive Consequences of Combat,” Col. Karl Friedl, director of the U.S. Army Telemedicine and Advanced Technology Research Center, explained why brain injuries have become more prevalent. The main cause: the improvised explosive device, or IED, a homemade device that has become the enemy’s signature weapon.
While some well-armored soldiers were able to survive the IED blasts, incurring no outward signs of damage, they later complained of dizziness and “having their bell rung,” symptoms consistent with the lesser-known mild traumatic brain injury (mTBI).
As many as 150,000 troops have been diagnosed with brain injuries, the Congressional Brain Injury Task Force reported last year, but it’s unknown how many suffer from mTBI. Mild brain injuries are less often diagnosed because soldiers often believe getting knocked around is part of the job. But over time, with each successive mild brain injury, the effects can become more severe.
The link between mild brain trauma and PTSD is being studied at the VA center in San Francisco by Dr. Gary Abrams, whose preliminary studies show that the overlap between PTSD patients and sufferers of mild brain trauma injury “is tremendous.” Abrams has yet to release definitive numbers.
During the next two years, Neylan expects the center will produce a few major findings in terms of possible treatments and advances in neuroimaging. One of the outcomes of the advanced brain imaging could be a prescreen test for soldiers to detect brains already showing PTSD tendencies. Neylan, who specializes in the role sleep plays in a healthy mind, is working on a study of police officers who are resistant to PTSD.
“We’re using this opportunity to also see why some people are able to walk away from these situations and live healthy lives,” he said, “and why others are not.”
Recent attempts to estimate frequency
Iraq and Afghanistan: The number of post-traumatic stress disorder cases is in dispute. The Pentagon estimates 30 percent of veterans from the Afghanistan and Iraq wars will be diagnosed with PTSD. Vietnam War: In 1988, a study by the Centers for Disease Control and Prevention estimated the rate of Vietnam vets with PTSD at 14.7 percent. But the 1990 National Vietnam Readjustment Study calculated the rate at 30.9 percent. Both relied mainly on self-reporting. In 2006, a paper in the journal Science added to the debate by estimating the rate at 18.7 percent. World War II: Though there was no official PTSD diagnosis until 1980, after World War II the term “shell shock” was reported by veterans troubled by combat experiences. Researchers such as Dr. Charles Marmar at the San Francisco VA center’s Northern California Institute for Research and Education estimate the number of WWII vets with PTSD is consistent with the 1-in-5 figures found in Vietnam and the Persian Gulf War. – Justin Berton
Experiments probe further into post-traumatic stress disorder
Four PTSD-related research experiments at the San Francisco Veterans Affairs Medical Center:
Nasal spray: Scott Panter is developing a battlefield-ready nasal spray for troops who suffer brain trauma. After the trauma occurs, the brain swells, causing tissue damage. Panter’s nasal spray, applied within 20 minutes of a trauma, would aim to stop the swelling process. Troops could carry the spray in their packs and self-apply or administer to others.
D-cycloserine: Dr. Charles Marmar is conducting trials on PTSD patients using D-cycloserine. The drug, which was originally used as an antibiotic for tuberculosis, has also proved to help lab animals “unlearn fear responses.” Given in small doses 30 minutes before a therapy session, D-cyclo is meant to help PTSD patients open up about their traumatic experiences and become more willing to engage in therapy. The hypothesis is that the group taking D-cyclo will make more and faster progress in therapy.
Blood/gene test: Dr. Lynn Pulliam is trying to establish a blood profile to diagnose PTSD. Using gene array technology, researchers will be able to take an RNA test, much like a DNA test, to determine whether a patient “tests positive” for PTSD.
Sleep experiment: Dr. Thomas Neylan is conducting a study on improving veterans’ sleep habits without drugs. Neylan said PTSD patients often feel anxious about sleeping, in part because they anticipate insomnia but also because they worry about nightmares. Subjects are coached to avoid substances that interfere with their sleep. “If we get them to sleep better at night,” Neylan said, “they’ll have fewer nightmares and feel better during the day.”