Can Researchers Find Better Treatments for Veterans with PTSD?
Two veterans turned Boston University researchers are studying PTSD to find better treatments for their former comrades
They Served Their Country. Now, They’re Serving Their Fellow Veterans
Two veterans turned Boston University researchers are studying PTSD to find better treatments for their former comrades
James Whitworth traces the path to his military service in simple terms: “I heard the call, and I answered,” says the Boston University Chobanian & Avedisian School of Medicine assistant professor of psychiatry. It was just after the attacks on September 11, 2001, Whitworth recalls, and he enlisted in the Army “to serve in the global war on terror.”
Whitworth deployed to Iraq, part of Operation Enduring Freedom and Operation Iraqi Freedom, along with nearly two million of his compatriots, all told. Just 21 years old and thrust into an unknown landscape with daily threats to his life, Whitworth says he exercised at his base to cope with the stressful situation.
It was certainly a DIY gym setup: rusty weights and heavy tires in a military tent.
“Anything and everything just to stay fit,” Whitworth says. “It was a source of de-stressing; a coping strategy to deal with the rigors of combat. And it just kind of stuck with me, it was like a kernel on the back of my head—I always knew that exercise was a helpful tool for dealing with stress.”
After Whitworth was honorably discharged, this kernel grew into full-fledged research questions for his graduate and then doctoral research. But that research took on new urgency when Whitworth’s close friend, a “battle buddy,” died by suicide, he says.
“It surprised a lot of us. And it really shook things up for me. I wanted to do something, anything,” he says. So, Whitworth refocused his exploration from the human-performance side of exercise, to its potential protective qualities against mental illness, stress, and trauma—particularly post-traumatic stress disorder, or PTSD.
Mark Logue was a sophomore at the University of Oregon, preparing for his final exams, when he received his call to service—quite literally.
“The phone rang, and they told me to pack my bags,” he recalls. “‘Your unit has been activated and you’re going to Operation Desert Storm,’” an official told him.
As a young person in the late 1980s, Logue registered for the US Army Reserve as a way to cover the cost of college and gain some worthwhile experience at basic training. It seemed like a fairly good deal: the reserves hadn’t been activated in nearly 20 years, since the Vietnam War. That changed in 1990, however, when reservists were ordered to active duty to serve in the Gulf War.
Logue, who worked in the reserves as a medical supply specialist, was sent to Stuttgart, Germany, to help expand a medical facility for combat soldiers wounded in the Gulf. Luckily, he says, the large-scale casualties his unit prepared for never materialized and, soon enough, Logue returned home, where his studies resumed. He remained in the US Army Reserve until 1997, when he was honorably discharged.
Trained as a mathematician and statistician, Logue charted a course for a career in genetics during his doctoral program. He found he could apply his mathematical and programming skills to address real health problems, a deeply gratifying experience.
Logue, currently an associate professor of psychiatry and biomedical genetics at BU’s medical school and of biostatistics at the University’s School of Public Health, was working on genetic studies of anxiety disorders and dementia when he was approached by Mark W. Miller, a researcher in the US Department of Veterans Affairs’ National Center for PTSD. Miller, a professor of psychiatry at BU’s medical school, had asked for Logue’s help in analyzing a set of genetic data from veterans.
He agreed. “I am a veteran and I’m always up for finding out new and interesting things,” Logue says.
Now, Logue and Whitworth both also work at the VA Medical Center in Boston’s Jamaica Plain neighborhood. They’re each seeking answers about PTSD by asking vastly different questions.
What Is PTSD?
Stress responses to traumatic situations are completely normal—a person’s natural flight, fight, or freeze response helps them respond to danger appropriately. For some, however, particularly combat veterans or people who’ve experienced physical or sexual assault, these natural physiological responses linger long after the danger is gone. This is PTSD.
Post-traumatic stress disorder is a condition that “impairs your functioning globally,” Whitworth says. People with PTSD may experience flashbacks or distressing thoughts, avoid people or places that remind them of the traumatic event, experience physical sensations like a higher heart rate or sweating, can have trouble sleeping, and more. It’s an embodied experience.
“This is not just a disorder that makes you sad, depressed, anxious. It impacts your behaviors, your ability to participate in your role in society,” Whitworth says. “And this translates to avoidance and isolation. And so people wind up staying away from a lot of the activities they used to enjoy; maybe they don’t feel safe going to a gym or a park.”
People with PTSD may also avoid exercise because the physiological sensations—elevated heart rate, breathing heavily, sweating—feel similar to a stress response, and they fear it will trigger a panic attack, or worse, Whitworth says.
But his research indicates that this avoidance is often the exact opposite of what will ultimately help.
How Can Exercise Help with PTSD Symptoms?
In a widely cited 2019 trial, Whitworth and his colleagues found evidence that resistance training (such as weight lifting) could have significant beneficial impacts on sleep quality and anxiety for people with PTSD. In subsequent studies, he’s found that improved cardiorespiratory fitness in post-9/11 veterans was associated with lower PTSD severity, and that as little as three weeks of high-intensity resistance exercise is a feasible intervention for symptoms in people with PTSD who aren’t otherwise seeking treatment for it.
“When we get people who have PTSD exercising, they feel better, there’s an impact and it reduces symptoms,” he says. “Is it a cure? A panacea? Absolutely not. But it is a coping strategy. It’s something that might be useful in augmenting other evidence-based practices, such as psychotherapy or medications.”
Whitworth and other physiologists and psychologists are still working to understand why exercise seems to be an effective therapeutic tool, but he says one potential factor could be the same one that makes people avoid exercise: it simulates a stress response—but in a safe and controlled environment. This kind of repeated exposure to those unpleasant sensations may work to normalize them, Whitworth reasons.
Another possible explanation is that exercise, and strength training in particular, builds senses of confidence, self-efficacy, and empowerment, Whitworth says. “Once you complete a challenging workout, or complete a heavy lift, you might think, ‘Well, I mastered this’ or ‘This one wasn’t so bad, maybe I can take on [a lift] that’s a little bigger.’ And that may augment your response to other similar or related stressors.”
Finally, Whitworth is interested in exploring the physiological adaptation that accompanies exercise. Perhaps a more efficient endocrine system—one of many side effects of going from “an untrained state to a trained state,” Whitworth says—helps people metabolize stress better.
Is There a Genetic Component to PTSD?
While Whitworth is interested in gym reps and sets, Logue deals in datasets: huge swaths of genetic data that might hold clues to the deep-rooted foundations of PTSD. He runs computational tests on millions of genetic variants across hundreds or thousands of genomes to find the variants that are statistically associated with a specific disease.
Once Logue identifies those statistically likely variants, other clinical researchers can use that information to identify better, more targeted strategies for the care and treatment of a particular disease.
It’s a technique that’s resulted in a number of important discoveries. Researchers have discovered genetic variations that contribute to the risk of developing type 2 diabetes, Alzheimer’s disease, heart disorders, obesity, Crohn’s disease, and prostate cancer.
Logue is part of a consortium of researchers pooling their datasets to search for clusters of genetic variants—small abnormalities in the DNA sequences that make up a gene—that are consistently present among people with PTSD.
Roughly a decade ago, Logue and his colleagues at the National Center for PTSD published the first ever genome-wide association study of PTSD; Logue was the lead author on its results, published in Molecular Psychiatry, an offshoot of Nature. They found a variant in a gene—the retinoid-related orphan receptor alpha, or RORa—that was associated with PTSD. Logue has copublished other papers since then, examining a possible connection between people with PTSD and the sizes of their hippocampus and amygdala, for example.
The genetic differences Logue and other researchers identified may not immediately lead to a cure, but they are an important starting point for clinicians—and could serve as markers on a genetic risk assessment for PTSD, Logue suggests.
Honorably Discharged, but Still Serving
For Logue and Whitworth, this work lives beyond the papers and the publications. It’s more like a calling, and one that could have a real impact for their fellow veterans and service members.
“It’s a personal connection,” Whitworth says. His work, which, like any, can be tedious at times, is made more profound because of that connection. “What gets me up in the morning for this sort of research, it’s not looking at the statistics and seeing significant p-values. It’s getting to talk to other veterans and knowing that the research that I’m doing is for them.”
That connection is true for many people who work at the VA, Whitworth says: “There’s this intrinsic desire to serve those who have served. And that’s powerful.”
It’s certainly true for Logue.
“Working at the VA spurs me on,” Logue says. “To get to my office [at the VA], I walk through the lobby with patients and ride with them in the elevator—these are veterans getting their care there. And then I go upstairs and analyze veteran data, and I’m hoping that the things we do actually help veterans and can lead to treatments; maybe not today, maybe not next week, but eventually.”
Whitworth’s research is primarily funded by the US Department of Veterans Affairs’ Rehabilitation Research & Development Service. Logue’s research is primarily funded by the VA Office of Research & Development, the National Institute of Mental Health, and the National Institute on Aging.
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