Toward an Objective PTSD Diagnosis

The possibility that only half the service members or veterans with PTSD seek treatment might be surprising to many people – but many people aren’t in the military, whose culture focuses on completing a mission, sometimes at the expense of fully expressing a mental or emotional problem. At all levels of its command structure, DoD has worked to break down this stigma against help-seeking behaviors.

One factor that may help to reduce this stigma is a reliable diagnostic tool that is as objective as the observation of a broken bone – a measurable neurophysiological change that provides a biological marker of PTSD, distinguishes it from other conditions, and perhaps even indicates improvement as a patient heals over time. Much of the work being done by VA researchers today, said O’Leary, involves brain imaging technologies: “There’s a lot of work using techniques such as functional magnetic resonance imaging [fMRI] or magnetoencephalography [MEG] that are trying to understand when PTSD occurs, how does the brain function differently than it did? Some of this work is showing that communication pathways in the brain that were active in people without PTSD are different than the pathways in people with PTSD. This provides the beginning of an understanding of what we need to deal with if we’re going to develop new kinds of treatment.”

“There’s a lot of work using techniques such as functional magnetic resonance imaging [fMRI] or magnetoencephalography [MEG] that are trying to understand when PTSD occurs, how does the brain function differently than it did? Some of this work is showing that communication pathways in the brain that were active in people without PTSD are different than the pathways in people with PTSD. This provides the beginning of an understanding of what we need to deal with if we’re going to develop new kinds of treatment.”

Last fall, for example, a VA/Duke University research team reported an association between PTSD and a smaller amygdala, an area of the brain critical to formulating fear and anxiety responses. In February 2013, investigators at the Minneapolis VA Medical Center (VAMC) reported that MEG scans of PTSD-affected brains revealed clusters of neurons that appeared to be locked in a trauma-encoding phase that made it difficult for subjects to encode new information. Later in the summer, researchers at the Boston VAMC’s Translational Research Center for TBI and Stress Disorders (TRACTS) suggested a linkage between PTSD and thinning of the cerebral cortex’s gray matter, which may result in cognitive impairment. VA scientists have also investigated linkages between genetic information and PTSD.

These markers can only, for now, be described as associative – it’s not possible to say whether the changes caused a person’s PTSD, or whether PTSD caused the changes, or neither. VA’s research program is aimed at identifying and characterizing biomarkers that can predict a person’s vulnerability to PTSD, indicate worsening symptoms, demonstrate a positive biological response to treatment, or indicate which neurophysical process to target with a treatment or drug.

“We want these biomarkers to help us understand who is going to benefit from the current treatment modalities we have,” O’Leary said, “such as prolonged exposure and cognitive processing therapy – and whom these modalities are likely to fail. We don’t know the answer to that question now, and it’s a very important question, because some people do marvelously with these therapies, and for other people it just doesn’t work at all. Either they don’t tolerate it and they’re not willing to complete the course, for whatever reason, or they complete the course and two months later they’re right back to where they were. So these biomarkers are a very, very important part of the portfolio.”

 

Better Treatments, Better Outcomes

Knowing which psychotherapies or medications will be most effective will be a critical tool in helping veterans with PTSD. Up to 60 percent of PTSD patients respond successfully to evidence-based psychotherapy – which sounds encouraging unless you consider the remaining 40 percent. While there are no medications developed specifically for PTSD, several drugs are used by clinicians to target specific symptoms such as anxiety or depression. Overall, very few treatment interventions target the underlying biological causes or mechanisms of the disease, which is why these areas of research are so important to VA and DoD researchers.

In the meantime, VA clinicians are working to measure the effectiveness of different therapeutic interventions – and different variations on those interventions, such as videoconferencing, couples therapy, or prolonged exposure therapy administered in a group setting.

While VA clinicians currently use psychotherapy in combination with antidepressants, sleep aids, and anti-anxiety drugs to attack the symptoms of PTSD, the VA is pushing to increase the use of psychotherapy, while also conducting trials that study drugs – such as the beta-blocker propranolol or the steroid mifepristone – designed to counter the intensity of memories that lie at the source of PTSD.

Often, the issue for veterans with PTSD isn’t so much emotional as functional. Their success, and therefore the success of any treatment they’re receiving, is measured by how well they deal with everyday life. Many veterans with PTSD do fine; others have problems with family, or difficulty holding down a job – which can put that person on a path toward worsening outcomes such as homelessness or substance abuse. VA is currently conducting a clinical trial of an intervention designed for these veterans called Supported Employment, in which clinicians provide PTSD counseling as well as counseling about how to get along in a workforce with a different culture and authority structure from the military.

While VA clinicians currently use psychotherapy in combination with antidepressants, sleep aids, and anti-anxiety drugs to attack the symptoms of PTSD, the VA is pushing to increase the use of psychotherapy, while also conducting trials that study drugs – such as the beta-blocker propranolol or the steroid mifepristone – designed to counter the intensity of memories that lie at the source of PTSD.

In the fall of 2012, ORD launched an ambitious Drug Development Initiative (DDI), aimed at forming public-private partnerships that may someday yield pharmaceuticals aimed at PTSD’s underlying causes. Studies will be administered through a Cooperative Research and Development Agreement (CRADA) with a pharmaceutical manufacturer. The VA issued its first request for proposals (RFP) in late 2012.

VA’s researchers are also looking at ways to combine interventions to see which treatments supplement or increase the efficacy of others. The VA and Army are working together, for example, on a clinical trial to evaluate the effectiveness of Trazodone, an antidepressant and sleep aid, to assist in the psychological treatments. “It’s absolutely crystal clear that although treatments such as prolonged exposure can be effective,” O’Leary said, “they are also very time-consuming. They don’t give rise to immediate relief. Maybe they’re not the best therapies. Maybe we can add a drug therapy, and use those therapies together in a way that makes them each more effective sooner.”

 

The Consortium to Alleviate PTSD

As part of the National Research Action Plan launched by the departments of Veterans Affairs, Defense, Education, and Health and Human Services in the summer of 2013 [see TBI article, this section], VA and DoD formed the Consortium to Alleviate PTSD, a collaborative effort between the University of Texas Health Science Center-San Antonio, San Antonio Military Medical Center, and the Boston VAMC, with the goal of developing the most effective diagnostic, prognostic, treatment, and rehabilitative strategies to treat acute PTSD and prevent chronic PTSD.

The consortium, said O’Leary, is taking the VA and DoD’s collaboration to a new and even more promising level. Goals of the consortium include confirming biomarkers for PTSD and TBI, identifying changes in brain function and circuitry after successful treatment, and identifying genetic risk factors.

“I think that is an immeasurable gift,” he said. “It shows the incredible generosity our veterans have towards each other, and towards the remainder of us in the country.” It’s a rare quality, one that inspires the VA’s researchers to seek solutions for returning veterans.

The work the VA and DoD have done, together and separately, has laid a critical foundation for helping service members and veterans with PTSD – but O’Leary said the future, at least in the near term, will require even closer coordination and stewardship of budget resources. “As we plan our work together with DoD, we are working more closely together to leverage the strength that each organization can bring,” he said, “so that as we approach this group of heroes, we can optimize the federal government’s investment in a coordinated way.”

PTSD is, in a sense, a veterans’ disorder, and the difficulty in finding a universally effective treatment is particularly frustrating for O’Leary and his colleagues, who see veterans with PTSD continuing to give service to others with the same disorder by giving their time to participate in these valuable studies. “I think that is an immeasurable gift,” he said. “It shows the incredible generosity our veterans have towards each other, and towards the remainder of us in the country.” It’s a rare quality, one that inspires the VA’s researchers to seek solutions for returning veterans.

“The kind of high-performance service they’ve given in the past, in the military,” said O’Leary, “they can give again in the civilian workforce. And we need to give them that opportunity, because when we do, they will pay us back a hundredfold.”

This article first appeared in the The Year in Veterans Affairs & Military Medicine 2013-2014 Edition.