I mentioned that there have been some genetic studies associated with Alzheimer’s disease. Another disease that some have related to military service is Lou Gehrig’s disease, ALS. As a result of that, VA has established a brain bank, collecting brains and spinal cords from veterans with ALS who volunteered to donate these after they died. VA investigators have done some very large studies on the genome of these patients with ALS, to try to understand genetic association. I can’t say that the work that has been done so far is providing a clear roadmap to how we treat ALS, but it does indicate, that as the technologies available to us are expanding, VA investigators are adopting them, trying them out and seeing whether they can help give us new insights into intractable problems that have sometimes, as in the case of ALS, been suggested to be of greater concern among veterans than in the general population.

VA’s 2009 study reported that 40 percent of Iraq and Afghanistan veterans enrolled to receive VHA care have at least one mental health diagnosis. So mental health is certainly a significant research concern. Has that always been the case?

There wasn’t a lot of emphasis on mental health at all back at the beginning of VA research. But you do see it beginning to show up early on in the 1950s and 1960s – and, in fact, studies done cooperatively by VA and the National Institutes of Health in the 1950s and early 1960s established the use of lithium for treating what we call bipolar disorder now. This was an amazing change, because at the time, mental health disorders were being treated primarily with psychotherapy. The Freudian model had really taken hold. And while the initial work on lithium was not VA work – in fact it wasn’t even done in the United States – when this work was adopted and pushed to a larger scale by this cooperation involving the VA/NIH collaboration, it really led to the understanding that yes, we can use drugs to effectively help people with mental illness. That also led to an explosion of research overall in what we call the discipline of biological psychiatry today.

The NIH has also proposed a million-person cohort for its database and is really building on the concept that we’ve shown can be achieved – getting information from electronic health records from a broader group of Americans and moving forward. That initiative and ours have a lot of places where there is complementarity. I think we have a clear commitment to be able to exchange data for those veterans that wish to participate in their cohort and for us to be able to learn from veterans that may be participating in the NIH cohort but aren’t receiving care within VA.

Then, immediately after this, the Vietnam War occurs, and much more concern arises in VA about the returning veterans. They are suffering flashbacks and things of that sort, and they are talking about it to a much greater extent than the World War II generation had talked about it. And the result is that large studies begin to be done on what becomes known as post-traumatic stress disorder, to define first of all how frequent it is, the course of it, and how we treat it. And those topics over time came to be a major part of our research portfolio, understanding the causes and consequences of PTSD.

There are three studies that we have funded coming out of the Vietnam War, and we’re now beginning to publish results that look at the long-term course and consequences of PTSD. One, called Health ViEWS, was a very large study that looked at health outcomes of about 5,000 women veterans of the Vietnam era. That doesn’t seem like a lot, in the context of women serving in the military today, but in terms of Vietnam, it was about half of the women who served overseas. A second, the Vietnam Era Twin Study, made it possible to begin to understand something about genetics in PTSD – in this case, the study design allowed one to find that PTSD is largely about combat exposure, but some of it is about genetic influence as well. Investigators could tell that by comparing identical twins with fraternal twins who served in combat.

A third study, funded at the same time, was the NVVLS, the National Vietnam Veterans Longitudinal Survey, which looked at outcomes in a large group of veterans, some of whom were not being taken care of by VA.

While all of this investigation into the background and the natural history of PTSD has been going on, there has also been work on therapy. One study that has had profound impact was a study by [Executive Director for the National Center for PTSD] Paula Schnurr, looking at the effect of cognitive processing therapy on PTSD and showing that this approach could be very effective in treating people with PTSD. It doesn’t help everybody. It doesn’t cure people, but it does reduce PTSD symptoms considerably. Interestingly, she focused on women who served in Vietnam, but other studies have grown into widespread adoption of cognitive processing therapy as a treatment for PTSD. And then since the adoption of that, a second therapy has become important and supported by evidence, called prolonged exposure. Now VA is undertaking a study to again compare these two established therapies to find out: Is prolonged exposure better? Is cognitive processing therapy better? Is one better for some people and the other better for other people? So it’s going through this evolution.

We’ve also studied the use of drugs for treating PTSD – but those studies have not yielded good pharmacologic interventions, so there’s a need to understand better what is happening in the brain in PTSD. And that’s being pursued in several different ways. One is studies using functional imaging technologies to see what communication looks like in PTSD. Investigators are using all sorts of technologies. Some of them are using something called functional magnetic resonance imaging. Apostolos Georgopoulos in Minneapolis has used something called magnetoencephalography, to look at communication pathways. And on the more basic side of things, a study building upon the Million Veteran Program has begun to look at the genetic heterogeneity, the actual gene changes, that may be associated with PTSD, building upon the Vietnam Twin study that showed there is a genetic influence.

The Million Veteran Program (MVP) is in its fourth year now, and has recruited more than 388,000 participants. It’s been suggested that it served, in some ways, as a model for the NIH’s Precision Medicine Initiative (PMI), announced at the beginning of the year by President Barack Obama. How are the MVP and PMI related?

The Million Veteran Program is already the largest epidemiologic cohort ever seen in the United States, and by this time next year, we’ll be at about half a million. We’ve actually shown that in the United States, you can create a large cohort of volunteers that are willing to participate in this kind of research, and we’ve provided at least one model by which it can be done.