Post-Traumatic Stress Disorder and the Role of Genetics
Guest: Dr Zhewu Wang – Psychiatry & Behavioral Sciences, MUSC
Host: Dr. Linda Austin – College of Medicine - Dean’s Office, MUSC
Dr. Linda Austin: Dr. Zhewu Wang is a psychiatrist at the VA hospital and MUSC Psychiatry, as well as Associate Professor of Psychiatry here at MUSC. Dr. Wang, you are doing some very interesting studies in combat-related post-traumatic stress disorder. I’m sure you’re working mostly with soldiers?
Dr. Zhewu Wang: Yes.
Dr. Linda Austin: From which wars?
Dr. Zhewu Wang: We’re actually recruiting patients from every kind of war: Vietnam, the Korean War, and World War II. Now it’s Iraq and Afghanistan.
Dr. Linda Austin: What questions are you trying to answer in the research that you’re doing with these veterans?
Dr. Zhewu Wang: The focus is on basic genetics and pharmacogenetics. Post-traumatic stress disorder is a unique disorder. Basically, it develops after traumatic events. In the veteran population, it’s mostly related to combat situations. After combat, some develop; some not, PTSD. The ones who develop PTSD will have some kind of psychological consequence afterwards.
Dr. Linda Austin: And some of those psychological consequences include what sorts of things?
Dr. Zhewu Wang: Of people who develop symptoms of PTSD, there are three clusters. The first one, basically, is that you’re re-experiencing symptoms.
Dr. Linda Austin: Re-experiencing symptoms, like fear; trembling?
Dr. Zhewu Wang: Like nightmares, flashbacks; images. You re-experience events. When that happens, people may experience strong emotions. They may cry. They may become terrified for a moment. And if this happens a lot, it will affect people’s lives. Sometimes people may become violent. People may wake up with their heart beating so fast that they sweat and cannot catch their breath, and they’re then unable to resume sleep.
The next cluster is, basically, avoidance.
Dr. Linda Austin: What kinds of things do they avoid?
Dr. Zhewu Wang: They usually try to avoid situations that might remind them, like broadcast news, or maybe a movie that might trigger a reaction. Furthermore, they start to become really alert to these situations and try to avoid crowds.
Dr. Linda Austin: I see.
Dr. Zhewu Wang: They do not connect with the outside world because they’re afraid something might trigger again.
Dr. Linda Austin: Now, your work looks at the pharmacogenetics, meaning what medications will work for these symptoms in patients with different kinds of genetic types.
Dr. Zhewu Wang: Mostly, that’s it. We want to see whether we can use genetic variations to predict who is going to respond, and who’s not going to respond, to medication treatment. That is the purpose of the research. Currently, treatment for PTSD is really limited. There are only two medications available.
Dr. Linda Austin: Which two medications are those?
Dr. Zhewu Wang: Sertraline, the first one, was approved in the early 90s.
Dr. Linda Austin: Or Zoloft.
Dr. Zhewu Wang: Yes, Zoloft. The second one is Paxil, or Paroxetine.
Dr. Linda Austin: How about other medications in that category, like Prozac or Lexapro? They haven’t been approved.
Dr. Zhewu Wang: But they are used. Those are called serotonin reuptake inhibitors. Their response rate is really low. If you’re talking response rate, it’s only 50 percent. The remission rate is even lower. It’s only 20 percent.
Dr. Linda Austin: So, in other words, only 20 percent of people become completely well. And only 50 percent have even a partial response to those agents. Is that right?
Dr. Zhewu Wang: Right.
Dr. Linda Austin: Including Paxil and Zoloft?
Dr. Zhewu Wang: Paxil, Zoloft, and other agents.
Dr. Linda Austin: So, you’re trying to do research to understand why some people respond, and others don’t?
Dr. Zhewu Wang: We conducted research, first; in a previous trial, with a civilian population. Now, we want to see whether we’ll see the same effects in veterans. Next, we want to see why some people respond, and others don’t. To save time, we’ll know who will and will not respond before we give the medication.
Dr. Linda Austin: Do you have preliminary hunches as to whether there are differences?
Dr. Zhewu Wang: There are differences. We conducted this study in a civilian population, as well as a veteran population. Both have indications of having one of the genes we investigated, serotonin transporter gene, which is the target of the medication. That [serotonin transporter gene] is the target of the medication we use for the treatment of PTSD.
Dr. Linda Austin: If somebody wanted to participate in one of these trials, would they have to be a veteran?
Dr. Zhewu Wang: Actually, yes.
Dr. Linda Austin: And, is it being conducted only here at the Charleston VA hospital, or across the country, at VA hospitals?
Dr. Zhewu Wang: Right now, only in Charleston and surrounding areas, as with a community outreach clinic.
Dr. Linda Austin: If a person wanted to participate in a trial, how would they go about doing that?
Dr. Zhewu Wang: We have study coordinators. We have advertisement. There are several ways that we try to recruit.
Dr. Linda Austin: Is there a telephone number?
Dr. Zhewu Wang: Yes.
Dr. Linda Austin: What is the telephone number?
Dr. Zhewu Wang: We have two coordinators right now. One telephone number is (843) 789-7502. The other one is (843) 789-7950.
Dr. Linda Austin: In this study, how do you go about getting a gene sample from the participants?
Dr. Zhewu Wang: We usually do this when we first do the assessment. The participants will go through a series of assessments to see what their symptoms are. Some patients may be re-experiencing. Others may be hypervigilant. After that, the participant will sign consent to participate in the study. Then we take them to our pathology lab. We have participants give about 10cc of blood; about two tablespoons, and we extract their DNA from that blood.
Dr. Linda Austin: I see. So, it’s just a needle stick? And then do you treat the patients with medications?
Dr. Zhewu Wang: Yes. After the initial evaluation, we know their symptoms and how severe they are, and then we start the medication treatment.
Dr. Linda Austin: Is there a placebo part to this trial, or does everybody get medication?
Dr. Zhewu Wang: Everybody gets medication.
Dr. Linda Austin: Everybody gets medication? And then you do rating scales?
Dr. Zhewu Wang: Rating scales at one, two, and three months.
Dr. Linda Austin: I see. How many participants, altogether, are you looking for?
Dr. Zhewu Wang: For the first study, which lasts three years, we’re looking for about 100. We’ve already recruited 30 or so.
Dr. Linda Austin: When did the study start?
Dr. Zhewu Wang: This study started around 2007.
Dr. Linda Austin: So, you’re really actively looking for more subjects at this point.
Dr. Zhewu Wang: Right.
Dr. Linda Austin: And they have to be veterans. Dr. Wang, it sounds like a very fascinating study. I’m looking forward to hearing the results. Thank you so much for talking with us today.
Dr. Zhewu Wang: Thank you.
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