Press Briefing on Chronic Fatigue Syndrome
Date Thursday, April 20, 2006
MR. SKINNER: Thank you for joining us today for this conference call where we’re going to be updating you all on some important research that we’re publishing in a journal on chronic fatigue syndrome.
With us today is the director of the CDC, Dr. Julie Gerberding, and two of our principle chronic fatigue syndrome researchers here at CDC, Dr. William Reeves and Dr. Suzanne Vernon.
To start the call, I’d like for the director of the CDC, Dr. Julie Gerberding, to talk a little bit about CDC’s work around genomics, why it’s important, and what we’re doing here at CDC with genomics.
You’ll find later, in talking with Dr. Reeves and Dr. Vernon, that genomics played a pretty important role in this particular study that they’re going to be talking about, and this is just one of a number of examples of important research going on at CDC around genomics and the role that it has in health.
And so Dr. Gerberding is going to spend a few moments, right now, just speaking about the big picture here, when it comes to CDC’s work and genomics, and how important it is.
So Dr. Gerberding, I’ll turn it over to you.
DR. GERBERDING: Thank you. Can you hear me okay? Tom?
MR. SKINNER: Yes.
DR. GERBERDING: Thank you. I’m delighted to have a chance to introduce to you Dr. Reeves and Dr. Vernon, who will be presenting the details of their work that’s just been published.
But I wanted to frame this in three ways. First of all, this is very exciting research in the field of chronic fatigue syndrome. It really is the first credible evidence of a biological basis for chronic fatigue syndrome, that’s come out in 14 articles, simultaneously, in the journal Pharmacogenomics. And I think it really reflects a remarkable confluence of a number of scientific advances really coming to bear on a problem of great importance to many people around the United States and one that’s had controversies in the past.
I think this is a very important step forward in the field of chronic fatigue research and we are delighted to have been able to contribute from the CDC as well as our collaborations with other investigators.
The second reason that I’m very excited about this particular press briefing is that this work illustrates the importance of the new field of public health or health protection genomics.
I think most people are aware of the Human Genome Project and all of the escalating science that this technological breakthrough has brought to bear on so many human diseases, but many are not familiar with why this is important for the population health.
In this particular example, by identifying specific genes and gene activities associated with people who have chronic fatigue syndrome, we’re really beginning to tease out the biological foundations of the manifestation of a disease in the population, not just at the individual level and this represents, I think, a very great illustration of how the whole enterprise of integrative biology and genomics can really escalate and accelerate our ability to understand diseases that up until this point may have been somewhat illusive.
This approach is likely to work on a number of other vexing public health challenges, for example, autism, where, again, there is an unexplained appearance of a disease in the population and there is a growing hypothesis, at least, that an underlying genomic basis may set the foundation for other potential environmental events that trigger the expression of the disease.
So this methodology is, in our opinion, a breakthrough, and one of the reasons why, at CDC, we have recently developed a new Office of Public Health Genomics, so that we can stimulate additional opportunities for this kind of integrative biology.
And the last point I would like to make is exactly that. The integration of people across multiple disciplines, that it takes to do this kind of work. That’s really been the theme of the development of the new CDC, our concept that the whole is greater than the sum of the parts, and by intentionally building linkages between scientists in different disciplines and different fields, that we will be able to accelerate and escalate our own road map toward achieving greater scientific advances as well as escalating their application and utility to people with important health problems.
So for all three of those reasons, the work itself and the importance to the field of chronic fatigue syndrome, the illustration of the value and importance of public health genomics as a very critical component of the science of public health, and then lastly, the illustration of how multidisciplinary, integrative biological approaches within CDC can really enhance and accelerate our ability to understand problems and make a public health difference.
So with that, let me turn it back to you, Tom, and again thank our investigators, Dr. Reeves and Dr. Vernon for their leadership and their excellent science.
MR. SKINNER: Thanks, Dr. Gerberding.
Now I’m going to turn it over to Dr. William C. Reeves, who is the principal CFS investigator here at CDC, that will provide you an overview of our work here, this new research, and then will be available, along with Dr. Vernon, to answer your questions.
So Dr. Reeves.
DR. REEVES: Thank you, Tom, and thanks to all of you for taking time out of your busy days to join us.
Before I get started, I want to take a brief moment to thank all of those who were on the research team. As Dr. Gerberding said, it was a massive joint effort, not just one person, and multiple institutions as well.
Without their hard work and expertise, none of it would have been possible. What I want to do first is provide you a little background information on chronic fatigue syndrome, or as I will usually call it, CFS.
The illness was first recognized in the late 1980’s, and despite more than two decades of basic and clinical research, and at least 3,000 peer-reviewed papers, we’re still learning a lot about it.
CFS is characterized by debilitating, medically and psychiatrically unexplained symptoms that include fatigue, diffuse problems sleeping, problems with memory and concentration and pain. At least a million Americans suffer from CFS, and its costs to society are staggering.
The average family in which someone suffers CFS forgoes around $20,000 a year in lost earnings and wages.
Today, CDC is reporting in the April issue of Pharmacogenomics some new and exciting results from the largest clinical study of people with CFS ever undertaken.
Hopefully you’ve been able to get into the journal’s Web site and read the articles for background information, but I’ll give you a brief overview of it.
Dr. Vernon organized the effort and will be able to answer your questions that you may have.
Basically, CDC scientists have worked with additional experts in medicine, molecular biology, epidemiology, genomics, mathematics, engineering and physics, to analyze and interpret information gathered from 227 people with CFS.
They were selected from thousands of individuals who participated in a population survey trying to learn about CFS.
The volunteers spent two days in a hospital research ward and during this study they understand detailed clinical evaluations, electrophysiologic measurements of sleep physiology, measurements of cognitive function which is memory and concentration, measurements of how their autonomic nervous system functioned, and extensive blood evaluations which included an assessment both of their genetics and of the activity levels of 20,000 genes.
The objective was to identify factors that could have caused or be related to CFS. The results are groundbreaking.
For the first time ever, we have documented that people with CFS have certain genes that are related to those parts of brain activity that mediate the stress response.
And that they have different gene activity levels, this is outside which genes are there, that are related to their body’s ability to adapt to challenges and stresses that occur throughout life, such as infections, injury, trauma or various adverse events.
Why is it important? Well, knowing that there is now a biologic basis for CFS will help us identify better ways to more effectively diagnose the illness and to come up with more effective treatments, including cognitive behavioral therapy, medications or a combination of both.
As the nation’s health protection agency, CDC is going to continue to study and learn as much as possible about CFS and other similar illnesses, in the hopes of helping people who suffer from them to lead more healthy and productive lives throughout all stages of their lives.
Thank you, and Dr. Vernon and I would be happy to entertain any questions you might have.
MR. SKINNER: Laura, we’re ready for questions, please.
OPERATOR: Thank you, and at this time, if you would like to ask a question, please press star followed by one on your touchtone phone. You’ll be prompted to record your first and last name.
If you would like to withdraw your request, you may press star two. Once again, please press star one if you would like to ask a question.
Our first question comes from Mike Stobbe from the Associated Press.
QUESTION: Hi, Doctors, thank you for doing this. Hey, hasn’t there been some research out of the United Kingdom in the last six to eight months, that has also identified genes that seem to be tied to CFS?
I was wondering,could you distinguish what’s new here versus that previous research from Glaxo and St. George’s.
DR. REEVES: I think both Dr. Vernon and I will reply to it. The major difference is that we were not trying to, in a simplistic manner, associate the illness, CFS, with a specific gene. What we were able to do in the very complex and multidisciplinary effort was to associate the illness, CFS, and those aspects of CFS, not only with a variety of genetic differences, all of which were related either to the hypothalamic pituitary adrenal axis, or to the sympathetic nervous system.
So we have an underlying biologic basis rather than a single simple marker, and at the same time relate that to the expression profiles or to the activity of all of the genes.
So we were much more trying to approach this from a physiologic or pathophysiologic process than, say, a single gene type was associated with it.
QUESTION: I’m sorry, I don’t understand. I understand you had a different approach, but did you find genes that previously had not been associated with CFS?
DR. VERNON: This is Suzanne Vernon. The study that Dr. Kerr reported on was a relatively small study that only measured the activity of the genes. I think they measured the activity of about 10,000 different genes, and they found, as a number of people have reported, including us, that they could distinguish different gene activity patterns between people sick with CFS and people not, healthy people.
And what we have shown now, in addition to the differences in gene activity, which we know occur, is that it’s a little bit more complex than that. There’s differences in the actual genetic makeup – the DNA code, that [could explain] the differences in the gene activity and also results in the manifestations of the illness itself.
So another big difference between what we’ve done and what others that have just looked at gene activity have done, is bring together a whole bunch of different types of data, not just gene activity but genetics. Gene activity, clinical information, physiologic markers, ways to describe how the person is feeling, and wrap that all together and try to generate a molecular profile of what that person that is sick actually looks like [editor’s note: the molecular profile of the person when they are sick].
DR. REEVES: This is Dr. Reeves. I’ll just add one other thing.
There is one major difference between this study and any other study that we are aware of.
For example, the U.K. study involved patients identified because they were attending a tertiary care clinic.
They were attending a specialty clinic for chronic fatigue syndrome. Our study identified people with the illness, who we found in a survey of a quarter of the population of Wichita, Kansas.
So we surveyed the population of an entire city. Fewer than 16 percent that had been diagnosed ever or treated for CFS. So the study is unique in that it is free of the biases that inevitably occur when only people who have already attended tertiary care clinics are involved.
MR. SKINNER: Next question, Laura.
OPERATOR: Thank you. Our next question comes from Joanne Silberner with National Public Radio.
QUESTION: Hi. I have two very different questions. I’ll ask them all at once.
The first is the cost of this study and the plans for further work. For example, Dr. Gerberding mentioned autism. Is anything about to happen with that?
The second question is can you, looking at the future, and look at how this would be used clinically and how soon it might be used clinically?
MR. SKINNER: Joanne, this is Tom Skinner. I can get back to you in regards to about, you know, in regards to other research involving genomics that we may be doing, you know, around other types of illness, and I’ll ask Dr. Reeves to respond to the cost of this study as well as your second question.
DR. REEVES: This study is part of an overall integrated research program, so the study followed after four years of surveillance of CFS in Wichita, a surveillance study trying to get at basically the clinical aspects of the illness.
We then had the two day in-hospital study which could not have happened without the first one.
The actual direct costs of the hospital study were about $2 million. Interestingly, the team approach for analyzing and working up the data, those people who were not CDC employees spent about a year of their time doing that at no cost. They were interested in getting at the data, at having a data set that was this complex involving physiology and the various markers. They did their time and put the time into the publications because they were interested in what would come out of it.
QUESTION: And then the clinical question?
DR. VERNON: Can you repeat your clinical question?
QUESTION: Looking towards the future, how could this be used clinically and when would that be likely?
DR. VERNON: I think it is not far from being able to be used clinically, because now, basically what we’ve done, is create, again, a molecular profile of individuals.
So perhaps we are closer to being able to predict how someone could respond to the types of medications, for example, that they’re currently taking to manage their symptoms.
QUESTION: In terms of diagnosis?
DR. VERNON: Say that again.
QUESTION: Could it be used for diagnosis?
DR. VERNON: Oh, absolutely. Absolutely.
QUESTION: How soon could that happen?
DR. REEVES: You realize that’s a terrible question!
DR. VERNON: Hopefully as soon as possible. That’s what we’re working for.
DR. REEVES: In terms of like a diagnostic marker–the question is a complex question.
What we’re getting at is the pathways involved. In terms of diagnosis, we use this information in our physician education program, to teach them about the illness so that they can approach it in diagnostic manners, not part of this publication, but part–the first publication that came out of the Wichita study, CDC has published a diagnostic algorithm using international–using a public domain available, and B, internationally validated instruments to diagnose the illness based on replicable criteria.
That’s apart from, you know, a biomarker. I can’t give a prediction on when that might happen.
DR. VERNON: I think what we’ve been able to show is that CFS is very heterogeneous, it’s not just one thing, so there’s probably not just one diagnostic marker.
We’ve actually demonstrated that there are probably at least four or five molecular profiles or groups of people that make up this complex of CFS, implicating perhaps subtle alterations in the system, that person’s, that is affected, more or less.
Does that make sense?
MR. SKINNER: Next question, please.
OPERATOR: Thank you.
Our next question comes from Rick Weiss with the Washington Post.
QUESTION: Thank you.
First of all, I want to say that at least I have not been able to read most of these papers, and the one or two that I can read on screen seems to be under a protected system that doesn’t allow me to print them, and I really think if you guys want to hold a big press conference and get some coverage for a 14- or 15-page package of papers, I think you need to make sure in advance, or at least now, that we can read them and not just count on your comments on a phone call to write a news story out of.
I think that’s asking a bit much and would be irresponsible on our part. So I encourage you to do something to make these papers available to us.
Complaint done, I have sort of two questions. One, I want to be more clear about the genetic differences you’ve seen that are not, you said, expression. To the extent the difference are not having to do with expression, are you talking about actual sequence differences or epigenetic differences, the importance to my mind being–I’m trying to figure out if you’re looking at something that’s clearly probably a cause versus perhaps something secondary to this disease.
The second question, after epigenetic versus sequence, is isn’t this a little bit circular?
I mean, people have made up a definition for CFS based on symptoms, and now you’re describing a collection of gene expression and other patterns that seem to go along with that.
It’s not clear to me how this improves the diagnostic or even, perhaps, the treatment options, but especially not the diagnostic ones, since you’re just looking through another lens at a collection of symptoms you’ve defined, in advance, to be CFS.
DR. REEVES: Okay. Let me deal with the symptom question first. The definition of CFS is based on symptoms. One could ask the question as to whether those symptoms are, in fact, real. But case definition was basically a consensus opinion has been done now twice of experts. We have done and published and actually have in manuscript a variety of studies looking at people who have CFS and other illnesses trying to do an empirical approach using factor analysis and other techniques to look at.
It is clear that CFS and other fatiguing illnesses, involve fatigue, they involve problems with memory and concentration, they involve sleep difficulties, and they involve various flu-like symptoms like pain, sore throat, etc. There is a fair amount of published information that the core construct is correct.
That having been said, is that core construct, is CFS a thing or is it a variety of illnesses? We do know that some CFS begins suddenly, all at once. Some people describe a very insidious onset. Again, CDC and others have published that the outcomes of those appear to be different. The risk factors for those appear to be different. And we have published that there are different gene expression profiles associated with sudden and gradual onset CFS.
One of the things we’re trying to get at in this study is within now the rubric CFS, are there subtypes that could be identified by these other measurements. The gene [polymorphisms or changes] that are involved, we’re talking about the sequence level methylation or epigenetic is a fascinating topic that we need to get into. But we’re talking about sequence variation.
The sequence variation that distinguishes individuals with with unexplained fatigue from those who do not have it involve both the HPA axis, those components of it that involve cortisol, and they involve the–the other groups involve the serotonin system or some signaling within the brain and the sympathetic nervous system.
We’re still trying to work out exactly what that means. So I don’t think it’s circular in that we’re trying to divide the pie and see if we can get better understanding of what might be the different parts.
MR.SKINNER: Laura, next question, please?
OPERATOR: Thank you. Our next question comes from Jenifer Corbett with the Dow Jones.
MS. CORBETT: Yeah. Hi. Thanks for taking my question. And I have to say, first, I actually dialed in a little late. I apologize if my question is already answered. And you have to forgive my ignorance on chronic fatigue. It’s been a number of years since I actually looked at it.
And I guess what I’m trying to figure out is that I know a number of years ago when there was sort of first reports of this kind of syndrome that was not necessarily taken seriously. It was, you know, some people questioned whether it was a real thing, a real disease. And I’m wondering, does your study, you know, refute that and/or has it been accepted now in recent years that chronic fatigue is a real condition?
DR. REEVES: I think there is no question the acceptance that chronic fatigue syndrome or CFS is a real condition. One of the most, one of the common stereotypes is that this is a bunch of hysterical upper-class professional white women who are seeing physicians and have a mass hysteria.
The fact that in the population studies, fewer than 16 percent, in the two population studies that have been done, have actually been diagnosed and treated for this means that in the population most of the people aren’t aware of CFS or that they might have it or anything.
At the same time in the population, using instruments like the medical outcomes survey short form 36, which are good, validated, and replicable measures of basically functional impairment, people with CFS–and, again, CDC has published this, as have others in clinic settings–are as impaired as a whole as people with MS, as people with AIDS, as people undergoing chemotherapy for cancer. Now, they’re not going to die. They don’t have something we can say that is the cause of it. But they are as impaired.
Our economic impact study shows that a family in which someone has this forgoes 20,000 a year in annual earnings and wages, and that a quarter of them are either on disability or out of work following the illness, indicates to us that it is a serious public health problem. Most people aren’t aware they have it.
A lot of the stress of our research is getting them into treatment. To some extent, studies like this, we use to, again, help in our physician education programs telling them about the pathophysiology and showing concrete evidence that it is real.
MR.SKINNER: Next question, Laura?
OPERATOR: Thank you.
Our next question comes from Delthia Ricks with Newsday.
MS. RICKS: Hello, there.
I just very quickly wanted to ask why Wichita, Kansas? Why was Wichita chosen as the site to study?
DR. REEVES: We chose Wichita for a variety of reasons. One of the reasons is historical. When CDC first started doing chronic fatigue syndrome and we did physician surveillance, Wichita was picked as one of the sites of physician surveillance. It was picked as that site because it is very typical of the United States and because there is not a lot of in and out migration with respect to physicians. So when we started the population-based study, we wanted to try to compare what we had seen in physician surveillance to what we saw in the population.
However, in addition, Wichita is, with respect to the census, its economic make up, its socio economic make up, basically a prototype United States. So it is a normal size U.S. urban center. Those are the reasons we did surveillance there. Because we had done the population studies and we wanted the clinical study to involve people identified from the population, we did the study in Wichita.
MS. RICKS: Thank you.
MR. SKINNER: Next question, Laura?
OPERATOR: Our next question comes from Casia Tsaseka from Jointandbone.org.
MS. TSASEKA: Hello. If I can go back to the question of whether CFS is a legitimate disease, if it seems a legitimate disease. Because I’ve read and heard from patients that they are very frustrated that sometimes their doctors aren’t taking them seriously. And you mentioned using some of your work already in physician education.
How would you say that attitudes of doctors have changed and over what sort of time span towards this disease? Is it being taken seriously now as a disease?
DR. REEVES: I think there are two–three answers to that question. One is that CDC’s chronic fatigue syndrome public health research program involves a fairly serious effort involving physician education, provider education. And we are in the process of publishing a paper showing the effects of that education. We actually have improved providers knowledge, attitudes and beliefs.
The second is, illnesses or things like chronic fatigue syndrome get more and more credibility as good research occurs. We collaborate with many people around the world doing research. Our own tracking of important or papers on chronic fatigue syndrome, both on treatment, on risk factors, on things of the UK study of gene expression was mentioned, are increasing and picking up every year. So it is becoming much more of a mainstream area for medical research. So, it, and I think thirdly in the UK there is now a concerted effort by the National Health Service to actually provide unified care and treatment for people with CFS.
You know, we’re trying to work in the U.S., which has a different system, with the providers, with medical schools, and with HMOs to get this more into their mainstream as well.
MS. _________: Could I just ask you to put some sort of time on that. So it was first reported as a syndrome in the 1980s. When would you say that it was becoming more accepted that it was a disease? Recently in the last five years?
DR. REEVES: I would say it has been an increase over the entire time period. If I track publications, the publications are going up, I wouldn’t say logarithmically, but something approaching logarithmically. I would say that clearly, in the last five years, yeah, there is a, you know, a much improved recognition, overall, of the illness.
The problems you mentioned are still there, they’re there with many illnesses like this, but, you know, I am very enthusiastic that this is changing.
I think that CDC, as the institution of the U.S. Government responsible for public health, has put, you know, a lot of effort into this. The agency is quite interested. The comments that Dr. Gerberding made as to how this fits into our public health genomics effort, into our effort across the life span, are all very telling.
CFS is not a simple disease like many of those that we look at. It is a complex illness with many ramifications, and CDC, NIH as well, but particularly CDC, from a public health perspective, is trying to approach this in all of its aspects, in all of its ramifications.
MR. SKINNER: Laura, we’ll take maybe two or three more questions, please.
OPERATOR: Thank you. Our next question comes from Helen Pearson from Nature magazine.
QUESTION: Hi. Thanks for taking my question. Because I also haven’t had a chance to look at these, or had access to these papers, I feel like we’re missing some specifics here about exactly what you found, like what genes are involved, what are they doing in the brain, and how exactly does this help us understand what’s happening in the brains of people that causes them to get CFS?
DR. VERNON: This is Suzanne Vernon.
We took a pathway-specific approach, so we targeted about 50 genes and about 500 polymorphisms in genes that are active in the HPA axis pathways. so that’s the hypothalamus pituitary adrenal axis.
The genes, of those 500 SNPs, five SNPs in three genes were very important, not by themselves but together, and those were the glucocorticoid receptor, the serotonin, and Tryptophan hydroxylase, are three of the very important genes.
Again, all are very important in the function of the HPA axis, which is the body’s stress response system.
DR. REEVES: And actually just to take it one more, we’re going to have to talk about how we can get various people access to the journals. Those were the genes that were in common of all of the groups. Other groups found some other genes, monoamine oxidase A and B, for example, are related to other parts of the HPA axis in the way that they chose to divide it up.
So, you know, we’ve intentionally, on this, tried not to–the genes that Dr. Vernon mentioned were key to all groups interpreting this, and perhaps further conversations, we need to figure out how we can get you the articles, and then how we can discuss that in more detail.
QUESTION: So is the idea here then that people who are susceptible to CFS encounter stresses in their everyday lives, like an infection, and they are less able to fight off that stress?
DR. REEVES: That is correct, and one of the things we have not mentioned in this, we’ve mainly focused this talk on the gene activity. One of the groups approached this through the concept of allostatic load, which is a physiologic marker, it’s a complex one, it’s put together of accumulated wear and tear on the body through continued adaptation to stress.
Those people with chronic fatigue syndrome have significantly increased allostatic load indices and there is a significantly increasing risk of that with normal medium level and high-level allostatic load indices.
MR. SKINNER: Laura, next question.
OPERATOR: Thank you. Our next question comes from Mike Stobbe with the Associated Press.
QUESTION: Hi. I just wanted to follow up. You all mentioned there are four or five profiles that were identified. That sounds like that’s new here.
Could you amplify just a little bit more about that?
DR. REEVES: Each one of the groups found, to some extent, different profiles, again, depending on their approach. One group did the approach, using what we identified as chronic fatigue syndrome, unexplained fatigue and not fatigue.
They found a variety of differences and they found that they overlapped. They didn’t look at the parts of the overlap.
Another group looked specifically and found three quite different groups of people with unexplained fatigue. One of them was more characterized by the extreme fatigue. The other was more characterized by heart rate variability, differences in cortisol, and basically sympathetic nervous system differences. The third was primarily menopausal women.
So that was that particular division. That group found that the genes that Dr. Vernon mentioned distinguished the three fatigued groups from those that were not fatigued and two of those genes distinguished between the fatigued groups.
It is a complex question, and we will have to apologize for not having the articles to everybody, and it’s kind of a copout, but perhaps best approach, when we can get availability of the articles and we could perhaps discuss those in separate queries.
MR. SKINNER: Laura, a couple more questions.
QUESTION: Thank you.
Our next question comes from Rick Weiss with the Washington Post.
QUESTION: Hi. Thanks. I want to follow up with the genetic business again also.
So it seems to me that if you’re gonna try to use these gene profiles, especially with regard to the sequence information, to help diagnose and perhaps get clues to treatments and mechanisms, the important thing is how well the various genetic profiles you’re finding really point to these groups, how well they define the groups, and I think–but correct me if I’m wrong–that maybe the positive predictive value is the best way to put that into numbers.
What is the positive predictive value of any of these genes or gene combinations, to really identify these people, and to what extent, you know, do people who don’t have the disease have these gene variants, or vice-versa?
How precise are these profiles matching up with the patient symptomatologies?
DR. VERNON: This is Suzanne. They all match up quite well. That’s how we were able to identify these genetic and genomic differences. They’re all very significant differences.
QUESTION: I mean, can you put some numbers on it so we can write about it.
You know, what are the odds, if you have this particular profile, that you are actually a person with this kind of disease?
DR. REEVES: Actually, I can’t give you those numbers and this is a confusing thing about this study. What we did is we did a clinical study in Wichita. We, as a simple case controlled thing, found that serotonin, TPH-2, and glucocorticoid receptor were associated with CFS and they had an odds ratio, which I don’t remember, quite frankly.
QUESTION: But are they up or are they down, or what direction–are they more active? Less active?
DR. VERNON: These are changes, these are actually genetic changes.
DR. REEVES: Now what we did, unfortunately, and again your question on access to the articles is a key one. We formed four teams comprised quite independently, some with people from CDC, some from other countries, some from other organizations, and we said we would like you, in any way you wish to do this, to approach this dataset. We would be interested in your computational and theoretical approach and we want to see what you find with your approach independent of the other teams, very similar to what Duke University does at CAMDA.
So we put them together as independent entities and we then, this particular issue of the journal reports four quite different approaches to this. The group that did allostatic load did a simple case control approach.
The group that, one of the first groups finding snips is actually in the article, did the approach we’re going to look at the fatigued and not fatigued people and we are going to empirically put them together, independent of whether they were CFS or not. Another group did a somewhat different approach.
What was key and came out of all of them was the same snips were found by those groups that chose to use snips. The same gene expression profiles were found in those that chose to do gene expression profiles. But everybody approached it somewhat differently.
So I can’t give a simple–glucocorticoid receptor has an odds ratio of six. So what it is doing, it is, to us, strong evidence of that involvement and it is to us how we structure the next look at this.
In other words, can I now subdivide in a study set to test the hypotheses that came out of this, based on that? In fact important–and would be shocked if you didn’t ask it–we are currently trying to replicate the findings of this study, both with a different approach to the Wichita sample, and with data that we have just gathered in a study of 30,000 people representative of the metropolitan, urban and rural populations of Georgia.
So we’re not saying yes, I have a marker, it is this. We’re saying a multidisciplinary approach, which I think is necessary to get at complex illnesses like this, they’ve very different approaches when smart people do something, but at the core of it was the same thing.
Now can we put it together in a more rigorous fashion in Wichita, and then, more importantly, can we replicate it in a completely independent sample in Georgia? Again population-based.
MR. SKINNER: Laura, we’ll take one more question.
OPERATOR: Thank you.
Our next question comes from John Rikert from Congress Quarterly.
QUESTION: Thanks. I was curious whether you know anything about how this particular genetic makeup that you identified as being associated with the disease occurs.
Is this something that can occur through, you know, environmental factors?
DR. REEVES: The genetic makeup–no. Our hypothesis that the HPA axis is involved in this, which is very clear in this allostatic load, is a physiologic marker of one’s accumulated adaptation to stress.
The working hypothesis is that the HPA axis and the brain is a plastic organ which changes its actual physical architecture depending on stresses that are accumulated over the lifetime.
So as people experience stress, and that can be childhood abuse, it can be childhood infections, it can be multiple injuries–all the stresses that we experience as these are experienced throughout the lifespan, to some extent the genetics determine how you are going to react to them, they determine how your allostatic load may accumulate, and more importantly, they actually determine your subsequent reaction to stress applied at a later time during the lifespan, and, you know, that is a very “hot” area for us, this again, the finding of the HPA axis, the adrenal part of it, and the sympathetic nervous system part of it, and the finding of allostatic load is making us do, again, some more very hypothesis testing studies in some other defined populations.
QUESTION: Thank you.
MR. SKINNER: Thank you, and thanks to all for joining us.
We’re going to be also reaching out to the journal to see what we can do to make sure those articles are unlocked.
A transcript from this press conference or this media availability will be posted on the CDC Web site within a matter of a few hours, so hopefully that will also assist you all in writing your stories.
So thank you for joining us.
OPERATOR: Thank you. This does conclude today’s conference call. We thank you for your participation. You may disconnect at this time.
[End of press conference.]
This page last updated April 20, 2006
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