Seth Norrholm, Ph.D.; Atlanta VA Medical Center and Emory University, PH/TBI New Investigator Award

My background in PTSD started when I was a graduate student. I was interested in how early life experiences can affect your mental health later in life. And over the last several years, I actually transitioned from doing animal models of PTSD to actually working with humans in PTSD, looking at the same sorts of things, the long-lasting effects of a traumatic event. So in this case, I'm now working with combat veterans from Operations Iraqi Freedom and Enduring Freedom, specifically looking at what psycho-physiological changes occur as a result of their traumatic experience.

So we look at a number of factors such as the acoustic startle response, which is a response that all mammals have. You hear a loud noise you're going to respond to it, and in humans, the best way to look at that is through the blink response. If you hear a sudden tone, you're going to blink your eyes in response to it. And that blink response is something that's characteristic to everybody so we all have a baseline response. And we use that baseline as our measure of normal startle activity. And you can modulate that startle activity through certain things like changing the context or to turn off the lights and then present the 108 decibel tone, too; you're going to blink much more than if the lights are on. That's just one of the evolutionary things that's characteristic of being human.

You can also use Pavlovian conditioning and that's what-very much what we're doing here. So what we do is we put an individual into a startle booth and they're presented with different shapes. One set of shapes is paired to an air blast and so they have a vest on with a tube that gives a very brief puff of air and it's aversive and so it's something that you don't want to happen. But it's by no means painful.

So if you pair one set of shapes with that blast of air while at the same time measuring the startle response, you get a much greater increase in the startle. That's called fear-potentiated startle. At the same time, we show a second set of shapes that's not paired to the air so that becomes a safety signal. So at the end of a session, if you show these repeatedly, one that's paired to the air blast and one that isn't, you get a very different response in the startle. So you get fear-potentiated startle to the danger signal, and you get lower startle to the safety signal. So that's the first thing that we're actually interested in is how well individuals that have been exposed to trauma can discriminate between danger and safety.

We then take that to the next level and we look at a process called fear extinction. And fear extinction is very important with stress and anxiety disorders because it's the fundamental process by which a lot of therapies are based. We then take those same two shapes and present them over and over again, this time without the air blast. And in healthy individuals what you see is that elevated startle response comes down over time. That's called normal fear extinction.

What we believe is that in PTSD and other stress disorders, the ability to extinguish fear doesn't drop off as quickly and so you get things like re-experiencing symptoms and pervasive PTSD symptoms. So what we hope to do through my experiments is to learn what's different about individuals with PTSD, so how well do they extinguish fear. And then we take it to the next level and we ask the question, is your inability to extinguish fear related to something that happened to you during a traumatic event or is it a consequence of that, or is it an inborn trait that we all have. You're more susceptible to develop PTSD because something is genetically different about you.

And so what we're doing is in addition to doing these fear extinction experiments, we're collecting genetic data from everybody so we can see if there are specific biomarkers that individuals who are poor extinguishers have that those that are good extinguishers don't have. So the ultimate goal as far as the military and how we can apply these things if you could do some sort of battery of tests that included the psycho-physiology processes and fear learning, you could almost get a sense of who is going to be more susceptible to developing PTSD upon their return from deployment by looking at those biomarkers before deployment. And then you can tailor treatments based on what you learned about someone's inability to extinguish fear.

Overall the response has been very good. Many of the people that come in to do the studies have that sense that maybe this will help me understand what I'm going through a little better and maybe it'll help future veterans understand what they're going through. So really, the response has been very positive.

My experience with CDMRP has been that they're more open to experimental designs that may not necessarily have a wealth of pilot data and in other words, they're going to take more of a risk if they think an idea has merit or has potential. It goes a long way to be able to tell research participants and patients that we are funded by CDMRP and DoD because it gives you a sense of credibility. It gives you a sense of this is an issue that government funding agencies are very interested in. And it gives us more credibility and more reason to bring in patients to our research studies.