Healing the injured brain: VA, DoD join forces on research to combat TBI, PTSD

In recent years, collaboration has increased between Department of Veterans Affairs (VA) and Department of Defense (DoD) researchers, especially in the areas of traumatic brain injury (TBI), post-traumatic stress disorder (PTSD) and other psychological health topics.

As many as 229,000 service members worldwide have received a clinical diagnosis of TBI since 2000. When comparing those who deployed to the overall diagnosed cases of TBI since 2005, almost 17,000 veterans of the wars in Iraq and Afghanistan have incurred a TBI in theater. Nearly 89,000 service members who deployed have received a PTSD diagnosis, compared to about 23,000 individuals who have never deployed experiencing PTSD. Many service members and veterans will recover -- depending on the extent of the injury or disorder -- but others will face greater recovery challenges. More than ever before in history, federal researchers are pressing to make strides in understanding these medical issues.

Ramping up the dialogue

DoD and VA researchers are charged with finding specific solutions that enable appropriate protection and treatment options for their respective populations of service members and veterans. The agencies "divide and conquer" within research topics while also recognizing the value collaboration offers for certain areas. For a topic like TBI, VA investigators typically take the lead in exploring long-term complications that might affect veterans, while DoD researchers often focus more on acute detection and immediate treatment to prevent further damage.

A major step forward in the VA-DoD partnership was the publication in 2011 of "common data elements," developed after a conference in 2009 that also involved the National Institutes of Health (NIH). Researchers from the different agencies can now "talk the same language" when studying brain and psychological disorders. They can similarly define injuries and use equivalent measures to diagnose conditions and gauge the effectiveness of new therapies, promising to speed progress toward new knowledge and improved treatments.

In addition to streamlining how injuries are defined and measured, researchers are working to ensure that funded efforts to advance medical knowledge and treatments are well-coordinated. The Defense Health Program held a psychological health and TBI research program review in December 2011 with the VA Office of Research and Development. Both agencies shared current research and development efforts, discussing areas where they may leverage investments to eventually maximize clinical practice and health services.

"While not the first collaboration effort, it was the initial forum of this kind where both DoD and VA science managers presented their funded research efforts in psychological health and traumatic brain injury. It was very beneficial to discuss the current state of science in these areas and examine scientific gaps where future research is necessary," Defense Health Program director Dr. Terry Rauch said.

Research topics presented at the meeting included PTSD, suicide, family challenges, resilience factors, substance misuse, depression and military violence. The two agencies identified future areas of collaboration to include areas like seamless integration of electronic medical records, prospective TBI cohort enrollment for research efforts and long-term imaging of veterans with TBI. VA's deputy chief research and development officer, Dr. Timothy O'Leary, stated that "collaboration and joint planning will maximize the impact of our medical research investments. This approach will allow us to more effectively translate the results of our studies into better care for service members and veterans."

Another signpost of increasing agency teamwork is the annual Trauma Spectrum Conference, held Dec. 8 -- 9, 2011 in Bethesda, Md. For the fourth year researchers from VA, DoD and NIH convened to share recent findings, forge research agendas and discuss how to best integrate new evidence into the care of injured service members and veterans.

According to VA chief research and development officer Dr. Joel Kupersmith, the presentations at the conference covered a "wide array of research related to psychological health and TBI, now under way in collaboration with our federal partners, which promise to create significant breakthroughs for active duty military and veterans."

VA Under Secretary for Health Dr. Robert Petzel adds: "The importance of federal agency collaboration cannot be overstated. As the first three trauma spectrum conferences have shown, bringing together high-caliber researchers, clinicians and stakeholders for a common purpose provides a solid foundation for tangible improvements in care."

Improvements in mental health care

VA-DoD research partnerships have already yielded the types of advances to which Petzel refers. A landmark clinical trial of prolonged exposure therapy for PTSD in women was spearheaded by VA's Cooperative Studies Program and National Center for PTSD and also involved Army doctor Col. Charles Engel, director of the Deployment Health Clinical Center, part of the Defense Centers of Excellence (DCoE) for Psychological Health and Traumatic Brain Injury. Results from the trial -- published in the Journal of the American Medical Association in 2007 -- and other research spurred an ongoing effort to train practitioners nationwide to use evidence-based psychotherapies to treat PTSD. Prolonged exposure therapy, in particular, is now strongly recommended in the VA-DoD Clinical Practice Guidelines.

On a related note, VA researchers in Atlanta and Honolulu, with funding from the Office of Naval Research, are testing virtual reality technology as an aid to prolonged exposure therapy. The researchers are developing and using virtual reality environments that recreate sights, sounds, sensations and even smells associated with combat zones.

In 2008, the DoD granted a $35 million award to establish the STRONG STAR PTSD Research Consortium. STRONG STAR is a multidisciplinary, multi-institutional research consortium under the leadership of The University of Texas Health Science Center at San Antonio. With 85 investigators at more than 20 partnering military, VA and civilian institutions the STRONG STAR Consortium has assembled an unprecedented collaboration of researchers and clinicians. This network unifies talented experts to make significant advances that will allow the DoD and VA to deliver PTSD treatment programs that are relevant, effective and feasible.

"Combat PTSD is unlike PTSD that occurs in civilians. It involves potentially traumatic events which are anticipated, numerous and diverse," said Defense Health Program committee chair and Army Military Operational Medical Research Program director, Col. Carl Castro. "Service members prepare to function, often while experiencing the numerous symptoms and reactions which occur with PTSD. The Defense Department's research strategy is to help the service member rapidly recover from PTSD related symptoms."

Another milestone in PTSD treatment has been the adoption into clinical practice of the drug prazosin, shown to ease trauma nightmares. Today, thanks to studies funded by VA, DoD and the National Institute of Mental Health, prazosin is part of treatment guidelines for PTSD and TBI. The drug, an inexpensive generic, is still being studied to arrive at a, "sharper definition of the range of symptoms that respond to it," says Dr. Murray Raskind, a psychiatrist at the VA Puget Sound Health Care System. Raskind suggests that given in small doses throughout the day, prazosin may also help daytime PTSD symptoms. He says a current trial of prazosin in 200 Army troops with PTSD is "the first placebo-controlled trial of a medication for a mental health disorder ever done in the active-duty military population." Additionally, VA's Cooperative Studies Program is testing the drug at 13 VA medical centers, and the trial is likely to yield definitive evidence about the drug's risks and benefits.

The Defense Health Program is sponsoring Dr. Amishi Jah at the University of Miami to examine Mindfulness-Based Mind Fitness Training (MMFT) developed by Dr. Elizabeth Stanley. The MMFT technique builds mindfulness skills to help users cope with stress and trauma. Early findings of the study show beneficial effects on working memory, attention and mood. Castro said Jha's "preliminary findings are promising. The study is investigating not just whether mindfulness techniques can enhance resilience in service members, but also how the technique works."

VA is increasingly funding research into complementary and alternative medicine (CAM) techniques such as meditation and mindfulness. A number of studies have already shown significant mental health benefits for veterans with PTSD from methods such as mindfulness-based stress reduction and mantram repetition.

Another important area of mental health research collaboration is suicide prevention. The VA Eastern Colorado Health Care System is part of a consortium set up recently by the Army and sponsored by the Defense Health Program to mesh military and civilian research. Dr. Peter Gutierrez of the Mental Illness Research, Education and Clinical Center at the Denver VA Medical Center is co-director of the group, named the Military Suicide Research Consortium. Some of his recent work has focused on suicide among those with TBI. The consortium is critical to ensuring that a clear scientific base exists to support suicide risk screening and prevention efforts.

"The Military Suicide Research Consortium is the most important effort established to address suicides within the military in the past century. It's an effort entirely dedicated to providing evidence-based approaches to preventing suicides," Castro said. Within a multi-disciplinary setting, researchers will develop screening and risk assessment measures to accurately identify high risk individuals and to develop prevention strategies and interventions for units, families and communities. More information about the consortium is available at http://msrc.fsu.edu.

Detecting brain injuries

Currently, there is no widely available objective diagnostic tool for identifying the presence and severity of brain injury. The Army alone has assessed over 60 different technologies in the last several years to meet this challenge. In 2009, DoD funded a company called Banyan Biomarkers to see if researchers can develop a blood test for detecting brain trauma, since it can be difficult for doctors to detect mild TBI through brain imagining. Col. Dallas Hack, a Defense Health Program committee chair and the Army director for the Combat Casualty Care research program, says he is encouraged by early findings. "This could rival the discovery of unique proteins in the 1970s that help doctors identify heart disease. It could in fact do for brain injury what that test did for chest pain," Hack said.

To develop a TBI-detecting blood test, Banyan Biomarkers and the University of Florida researchers are studying several different protein fragments. These proteins are produced at increased levels by the injured brain and spill into the blood stream after a trauma. Among other diagnostic research efforts, this one has yielded promising preliminary findings. An evidence-based, Food and Drug Administration-approved TBI biomarker blood test "would change medicine entirely," Hack added.

Progress on brain injury treatment

The Defense and Veterans Brain Injury Center (DVBIC), part of DCoE, is a DoD-VA collaboration that helps ensure high-quality care for active duty military, their dependents, and veterans with TBI. The program also conducts innovative clinical research. In late 2008, DVBIC researchers published the results of one of the first studies of its kind: a randomized clinical trial comparing different approaches for cognitive rehabilitation. The study involved 360 veterans and active-duty troops with moderate to severe TBI. Both treatment approaches proved effective. In fact, one year after treatment, six in 10 study participants were employed and living independently. Lead author Dr. Rodney Vanderploeg and colleagues wrote: "This is remarkable, given that none were capable of work or independent living at baseline." They noted, also, that 90 percent had brain injuries that were considered severe.

Another angle on TBI research is exploring the sensory deficits that often occur in blast injuries. In collaboration with Army colleagues, researchers with VA's National Center for Rehabilitative Auditory Research are investigating "central auditory processing" -- the way speech is interpreted into meaningful messages -- in combat veterans who have been exposed to blasts. The work may lead to new approaches to improve communication for those affected by TBI.

A joint DoD-VA brain-focused clinical effort includes a partner from private industry -- San Francisco-based Brain Plasticity. The company's chief operating officer and senior scientist, Dr. Henry Mahncke, says the computer-based training developed by the firm is now being tested for TBI in a defense-funded study at several VA and DoD sites. "The program is based on the basic science of brain plasticity -- new science that shows that anyone's brain, young or old, healthy or injured, is capable of tremendous change and improvement if we ask it to do the right kind of exercise," explains Mahncke. He says the intervention promises to "change the structure, function, and chemistry of the brain."

Leaders in brain imaging

Researchers are using advanced brain imaging to gain a deeper understanding of TBI and PTSD. Some of this work takes place at the Neuroscience Center of Excellence at the San Francisco VA Medical Center, a joint effort between VA and DoD. The program focuses on improving diagnosis and treatment of TBI as well as PTSD and other neurological conditions that may affect combat veterans. Begun in 2004, the center was among the first joint VA-DoD research efforts in neuroscience, and since its inception it has received more than $35 million in defense funding.

The program is nested within the larger Center for Imaging of Neurodegenerative Diseases, which houses a powerful seven Tesla MRI machine. Part of the research involves looking for signature brain changes associated with TBI, PTSD or both. Director Dr. Michael Weiner, an Air Force veteran, emphasizes that PTSD involves physiological and anatomical changes in the brain, even though -- unlike TBI -- the condition may not be brought on by external forces to the head. "Generally ... there are structural and functional biological changes that can be detected in people with PTSD, and ... these changes affect areas that make sense -- they are areas involved in our fear response."

Similar work is going on at VA's "Neurons to Networks TBI Center of Excellence" in Houston. Center director Dr. Harvey Levin explains the findings from a recent functional MRI study of 30 veterans: "By using a cognitive task, we found that the mild TBI group had higher activity in the prefrontal cortex, whereas those veterans with PTSD had reduced activity. This study demonstrates the possibility of using fMRI to dissociate between these two conditions and is consistent with previous studies indicating that PTSD tends to diminish prefrontal cortical activation. These results suggest that brains of veterans with mild TBI have to work harder on this task as compared to those veterans with PTSD and could be used to develop future diagnostic tests to yield better therapies for our veterans."

Researchers at the VA, Boston-based "Translational Research Center for Traumatic Brain Injury and Stress Disorders (TRACTS)" are focusing on how TBI, stress disorders and chronic neuro-degeneration from brain injury can be detected, monitored and treated. TRACTS co-director Dr. William Milberg describes this approach as "creating the most detailed and technologically advanced picture of the brain to determine any cumulative effects of multiple brain injuries." TRACTS director Dr. Regina McGlinchey adds: "The strength of this center is that we have a team that can integrate both biological and psychological mechanisms into the bigger question of how chronic traumatic encephalopathy is connected to the long-term brain and mental health of veterans."

Meanwhile, VA researchers working with Marines at Camp Pendleton have found that a combination of two imaging technologies -- magnetoencephalography and diffusion tensor imaging -- picks up subtle brain injuries that go undetected in conventional CT and MRI scans. The first type of scan detects signals neurons give off when they fire. The second shows abnormalities in the brain's nerve fibers. According to lead researcher Dr. Mingxiong Huang, injured brains generate pathological low-frequency brain waves -- like those seen in normal patients during deep, dreamless sleep. Damaged neurons become like frayed wires, unable to conduct impulses efficiently. Between the two types of damage, Huang believes researchers may find the TBI signature patterns they are seeking.

Also in San Diego, DoD is funding VA psychiatrist Dr. Murray Stein who is leading a $60-million, five-year, 10-site clinical consortium that is focused on both preventing and treating PTSD and TBI. The wide-reaching research effort covers topics ranging from the genetics and neurobiology of the two conditions, to new interventions aimed at helping injured service members, veterans and their family members.

The long view: Studies track deployed troops over time

Several large-scale efforts now under way by VA and DoD promise to yield important insights into PTSD and other effects of military deployment.

"Neuropsychological and Mental Health Outcomes of OIF: A Longitudinal Cohort Study" is examining the possible lasting health effects of Operation Iraqi Freedom. The effort involves several hundred soldiers who had taken part in an earlier VA-DoD study. Researchers hope to learn about any enduring effects of war on mood and stress symptoms, cognition and reaction skills and daily function.

The "Millennium Cohort Study" is the largest prospective health project in military history. Now in its 10th year, the study is funded by DoD and supported by VA and other researchers. Almost 150,000 service members have participated so far, about half of whom have been deployed to Iraq or Afghanistan or surrounding regions and a third of whom are women. The study has already produced valuable knowledge and resulted in dozens of scientific publications, addressing mental as well as physical health. A study published in May 2011, for example, traced the role of pre-deployment psychiatric conditions and deployment-related physical injuries in the development of post-deployment PTSD.

The "Millennium Cohort Family Study" is sponsored by DoD and being conducted at the Naval Health Research Center, with collaboration from Duke University and New York University. Military spouses will complete questionnaires on a variety of topics so researchers can assess the impact of deployment on family behavioral health, quality of relationships and related outcomes. The study aims to identify family vulnerability, stressors, and resilience factors that will provide an evidence-based guide for intervention.

Along similar lines, the Marine Resilience Study involves VA and DoD researchers and more than 2,000 Marines. The troops are evaluated one month before deployment and then at three time points after they return. The researchers are looking at many factors that might be associated with resistance to and risk for PTSD, ranging from biological to psychological, social and environmental factors.

Study collaborator Dr. William Nash, a former Navy psychiatrist who deployed to Iraq with the 1st Marine division in 2004, says: "Finding objective, physical markers for PTSD in our study would go a long way toward reducing the stigma. There are still too many military service members, including health care professionals, who don't believe PTSD is a real illness resulting from real injuries to the mind and brain, but instead think it is caused by a personal weakness. If we can show them biological markers for PTSD, service members will better accept that PTSD is no more their own fault than any other wound of war."

These studies are collecting valuable mental and physical health information prior to deployment, and then conducting assessments after the deployment ends. Such efforts will help researchers pinpoint the impacts of military service on this and future generations of service members and veterans.

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