Search for tag: "altitude"

Interviewer: Could altitude play a part in depression? If so, could something as simple as a dietary supplement fix the problem? Up next on The Scope.

Announcer: Examining the latest research and telling you about the latest breakthroughs. The Science and Research Show is on The Scope.

Interviewer: I'm talking with Dr. Perry Renshaw, professor of psychiatry at the University of Utah. He's currently seeking crowdfunding for a project on Experiment.com to improve depression caused by living at high altitude, a particularly worrisome problem here in Utah.

Dr. Renshaw, you're researching the effects of altitude on depression. What led you to make that connection in the first place?

Dr. Renshaw: Well, you know the risk of being too long winded . . . I and my wife moved here as part of the USTAR program in 2008. In conjunction with that move, we started working at the VA Research Center on Mental Health. The assigned focus of that center which is called a MIRECC is on suicide. Never having done suicide research before, I was casting about for a topic. So this remarkable map of the United States which showed that across all the different states in our country, it was really the Rocky Mountain states that had a much higher rate of suicide than other places, which led to the idea that maybe that had something to do with the altitude in the Rocky Mountain states.

Interviewer: Do we know that this suicide is due to depression and not something else like suicidal pressures or other factors?

Dr. Renshaw: Well suicide is a complex phenomenon. People chose to end their life for a variety of reasons. However, in general, diagnosis like depression are pretty strongly linked to suicide. If we just look at rates of depression in Utah, there are two unfortunately. We seem to lead the nation in terms of the prevalence and severity of depression affecting both adolescence and adults.

Interviewer: So how are you addressing this problem in your research?

Dr. Renshaw: The most important goal that we have for our research is not so much to find the problems and understand them, but to rather to use that understanding to come up with better treatments. Really it's not going to be practical for every depressed Utahan to move to the coast or to some place at sea level. That would be a rather drastic intervention. The goal is really to see if there are simple things we could do that would just help people to feel better.

Interviewer: You're doing some investigations in rats. Why is that important?

Dr. Renshaw: Our motivation in looking at animals is to give us a way to test potential new treatments because we can do that much more quickly and effectively and safely, at least as a starting point in animals before beginning clinical trials. Well the test we use in animals is with rats. We ask rats to go swimming, which seems sort of like a silly thing but it's been a test that's widely used in trying to figure out what's going to be a good anti-depressant both in terms of changing animal behavior and in terms of people who have depression.

What we see is being the real benefit of having an animal model is that it gave us clues as to what's changing in the brain. What we find is that particularly for the female animals, they don't swim as much as you go up in altitude. We don't actually take them up to Park City. We have a hypobaric chamber. It can simulate any altitude we want. Particularly for the female animals in this experiment, the higher up you go, the more and more depressed they look. It's really a straight line showing that whatever else is happening in animals that makes them behave as if they're depressed to altitude is really a critical factor.

Taking the example of creatine which is the same substance, a natural product used by weight lifters and high school football players to build strength. Well if we use it on our animal model, the male rats couldn't care less. It has really no effect on their behavior using our simple test of a swimming test, which is widely used to study the effects of potential treatments for depression.

The female rats, though, are sort of off the charts thinking that this is really a powerful anti-depressant.

Interviewer: What is creatine and how is it connected to this effect that you are talking about?

Dr. Renshaw: So creatine can be converted into phosphocreatine, which is the highest energy compound that exists in the body. It exist predominantly in skeletal muscle and in brain. It's sort of a battery for anything that you need to have a very rapid supply of energy. So it becomes very important and it's been studied a lot in athletes in terms of their athletic performance. But it's only the 5 or 10 years that scientists have turned their attention to the brain.

In the area of depression, if you have low levels of phosphocreatine in the brain, you're very unlikely to respond to any kind of anti-depressant treatment. So having a high enough energy level in the brain if you will is something that really facilitates a good response to treatment.

In Utah, what we see is a lot of treatment resistant depression in children and adolescents. So we started the trial of creatine in adolescent young ladies who've not had a good response to treatment. This is an on-going trial funded by the National Institute on Mental Health. What we're doing is just adding creatine to a standard anti-depressant treatment, and so far the results are very encouraging, very positive.

Interviewer: What you're observing, is that if you add creatine to the regimen in addition to taking these anti-depressant drugs then you do see some improvements?

Dr. Renshaw: That's right. The first seven young ladies we studied, just to test the idea with our local population. Six of the seven were suicidal at times. None of them were working. None of them were in school. By the end of eight weeks of treatment, the group as a whole, and in fact every single individual have lost about half of their depression symptoms. Four of them had gone back to work or to school, and the outcome was really very positive.

Side effects to the creatine were really very modest because were using doses that have been well established to be safe for children particularly. When we look at football players, it's been estimated that approximately 60% percent of American high school football players take creatine as a nutritional supplement to build strength.

Interviewer: Right. So this is something you can just get at your local health food store, right?

Dr. Renshaw: Absolutely. Although in general, you don't want to start anything that's going to affect how you feel or how you behave or how you think without checking with your doctor.

Interviewer: It's kind of striking to me that there are all these kind of fancy drugs around but you may be coming back to sort of natural supplements to help people with this problem. I mean, that's kind of good news in a way.

Dr. Renshaw: I think so. If you look at what drives the use of any particular treatment in medicine, it's often having a company that is marketing a product that they really want to sell. Natural products tend to be inexpensive and you can't make a lot of money selling them, which means that there's not necessary be a lot of research using this compounds. Frankly, that's been a challenge for us raising funds to do treatment studies that are sort of Rocky Mountain or Utah specific.

We think it's really important because if you're depressed, feeling better is really going to make you happy, your family happier. You're probably going to be better off economically as your work performance goes up. There's a lot to be gained by treating depression effectively.

If we look at the increase rate of depression in the state of Utah at 25%. We think that this is probably due to the altitude. The economic consequences of that for the state are something like $200 million, direct and indirect losses. So addressing this problem has a lot to gain not just for those people who are depressed, but for the state economy as a whole.

Announcer: Interesting, informative, and all in the name of better health. This is The Scope Scientist Health Radio.

Announcer: Examining the latest research and telling you about the latest breakthroughs. The Science and Research Show is on the Scope.

Interviewer: Tibetans thrive in the high mountains of the Tibetan Plateau, conditions that most others just can't survive in. My guest, Dr. Josef Prchal, a professor in internal medicine at the University of Utah, led a study; identifying an 8000-year-old variation in the DNA sequence of Tibetans that help explain their amazing adaptation.
Today, I'm also joined by first author of the study, Dr. Felipe Lorenzo, and Dr. Tsewang Tashi, who is also an author on the paper and a native Tibetan. Dr. Prchal, Tibetans and lowlanders like us adapt very differently to high altitude conditions, what are the differences that you're interested in?

Dr. Prchal: The obvious difference is that if lowlanders go to very high altitude, they may die, but if you stay there for a long time, there are some chronic consequences which are not suitable for reproduction and for thriving in this high altitude. There are many and some of them we will not fully understand, but one of them is, what we call, pulmonary hypertension; that the pressure on the lungs is so high that it interferes with the circulation and you get, eventually, heart failure.
The other well-known adaptation is the level of oxygen tightly controls how many red cells we make. It means if we don't have enough oxygen, we make more red cells. So if you go to high altitude where the oxygen pressure is lower we make too many red cells. That's called polycythemia. That means the blood gets too thick and it's not very suitable for them, but it has been known that most of the Tibetans have a normal level of hemoglobin in very high altitude and this is something which gave us tools to study this.
And we selected then the Tibetans who had high hemoglobin and low hemoglobin, and that allows us to look at the genetic differences in these two populations. And with a graduate student here from department of genetics, Tatum Simonson, we selected these two population, did, at that time, the state of our genetic studies and we were able to look at the fingerprint of the genes of interest. We selected about 300 genes and 10 of them had clearly selected, that means they achieve much higher frequence in Tibetans, in those who were adapted well to high altitude.
And these adaptation mutations then must have some beneficial effect and so that was the first lead. And at two of the genes, which are selected, had something to do with how the body responds to oxygen, so one of them, a gene called PHD2 is a negative regulator of master regulators of response to hypoxia which is called HIF.

Interviewer: And what does the gene do?

Dr. Prchal: It decreases the over-response to very low oxygen. So sometimes our physiological responses may be detrimental. And so by modulating the intensity of the response, I think that was one of the benefits.

Interviewer: Dr. Lorenzo, you've been on the trail of this gene for a long time. It must have been satisfying to find it at last.

Dr. Lorenzo: It's really a challenge actually. Sequencing that region of a gene we just recently reach took me like six to nine months of trial and error. Finally, when we get it, it was just like you win a lottery and it's something to move on.

Interviewer: So when you saw it, you knew that was the one.

Dr. Lorenzo: Yes, because it's reproducible, it's there, it's common in our sample, and not common in the controls, so there's a story to tell.

Interviewer: So if the variation was selected for it, it must be important.

Dr. Prchal: If a gene happens to be beneficial in a given environment, with each generation the prevalence of these genes will increase. And so, again, if the Dr. Lorenzo's mutation of variant is find of 85% of Tibetans, it must be beneficial.

Interviewer: Dr. Tashi, you're a native Tibetan, it sounds like you guys went through great lengths to gain acceptance by the Tibetan community.

Dr. Tashi: So I join here in 2012 in University of Utah and one day Dr. Prchal approached me while I was in clinic and he was very excited that I was a Tibetan and I was kind of surprised.

Interviewer: Who's this guy?

Dr. Tashi: Initially, it seemed to me that he just wanted some blood and I said, "Well, that's easy. I can get some friends and get some blood."

Interviewer: Were you one of the ones sequenced in this study?

Dr. Tashi: Oh, of course, yes.

Dr. Prchal: He is.

Dr. Lorenzo: One of the first ones.

Dr. Tashi: And later on as the study progressed, I realized the significance of the whole study and this is a new potential, a very groundbreaking discovery, in a sense, and the importance that it would have, not only for the science as a whole. But being a Tibetan and also something uniquely Tibetan that's potentially the result of this, then we decided, okay, we should go and get involved more Tibetan. Actually, we went there twice and they don't really like to give blood because when you hear blood, it's kind of "Wow."

Interviewer: Yeah. But once you were able to explain it to them, and probably the fact that you are a Tibetan yourself and you're willing to undergo this, that helped them to accept it?

Dr. Tashi: Yeah, that was one of the major helping point.

Dr. Lorenzo: This is why Tsewang is a key for the success of this study because Dr. Prchal and I went actually to the community. It took us six to nine months talking to them and we got two samples.

Dr. Tashi: It's really difficult.

Dr. Prchal: We were well received.

Dr. Tashi: When it came to collecting blood, they just backed out. So it's really a key to get them into the study, and it really did go well.

Interviewer: And in the end, how many took part, the Tibetans?

Dr. Tashi: For here, locally, we have 26 or 28 and then I brought it 60 plus.

Interviewer: Wow.

Dr. Prchal: Well, began probably more than 200 samples.

Dr. Lorenzo: More than 200 in China.

Dr. Prchal: Yeah, more than 200 samples.

Interviewer: It's important for you to get letters of support from high leaders in the Tibetan community, including the Dalai Lama.

Dr. Prchal: The Dalai Lama was contacted by a principle physician called Dr. Dorjee, who easily organized all these Tibetan health care in exile community and that only happen through Dr. Tashi. And Dr. Dorjee has contacted Dalai Lama, explained to him what we try to do, and Dalai Lama felt a better of the Tibetan adaptation would be helpful to Tibetan community, but also to humanity at large. And I think that Dalai Lama is very ethical man and when it comes to ethic issues, I think it's very important to him.

Interviewer: What are the implications of this work?

Dr. Prchal: There are many human disorders which are regulated by oxygen; not only the pulmonary or lung diseases, brain edema, but also cancer. So we think that delineation of this Tibetan adaptation and deeper understanding of this can eventually lead to better understanding of common human diseases.

Announcer: Interesting, informative, and all in the name of better health. This is The Scope Health Sciences Radio.