Gerberding - huh - did this come out of her mouth????

[Guest guest]

Has Gerberding been talking to Dr. Amy Yasko????

Press Briefing on Chronic Fatigue Syndrome - Interview

by CDC

ChronicFatigue.com

05-23-2006

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. Gerberding, and two of our

principle

chronic fatigue syndrome researchers here at CDC, Dr. Reeves and Dr.

Suzanne

Vernon.

To start the call, I'd like for the director of the CDC, Dr. 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. 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: , 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. '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, .

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.

QUESTION: Okay.

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?

QUESTION: Uh-huh.

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: , next question, please?

OPERATOR: Thank you. Our next question comes from Jenifer Corbett with the Dow

.

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, ?

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, ?

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: , 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: , 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: , 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: , we'll take one more question.

OPERATOR: Thank you.

Our next question comes from 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 URL:

http://www.cdc.gov/od/oc/media/transcripts/

t060420.htm

United States Department of Health and Human Services Centers for Disease

Control and

Prevention Office of Communication Division of Media Relations