More on Chronic Fatigue
August 2nd, 2006,I’ve had a chance to read the Centers for Disease Control press briefing transcript that I mentioned in yesterday’s post. The briefing explains that the CDC study on chronic fatigue syndrome (CFS), which used data from patients in Wichita, Kansas, resulted in 14 scientific articles published simultaneously in the journal Pharmacogenomics (April 2006 edition). It used new approaches in integrative biology and genomics and represents a new field called public health genomics. (CDC has actually created a new Office of Public Health Genomics.) It involved researchers from the fields of medicine, molecular biology, epidemiology, genomics, mathematics, engineering, and physics. The leaders of the research feel it can be used to study other complex diseases such as autism.
The briefing is highly technical and in many ways beyond my capacity as a non-scientist, and I won’t comment any further on it now. Suffice it to say that it seems to represent an important step in identifying a biological basis for chronic fatigue syndrome. It also makes me wonder about the specifics of my own genetic makeup, particularly in relation to my own experience of the effects of stress.
Below are what I’ve judged to be the most important parts of the briefing. Ellipses and stars indicate where I’ve made cuts:
…DR. REEVES: 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.
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DR. REEVES: [W]e 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,…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…
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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.
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DR. REEVES: The sequence variation that distinguishes individuals 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…
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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.
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DR. REEVES: [I]llnesses 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.
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DR. REEVES: [T]he 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.
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DR. 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.
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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.
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QUESTION: 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.