Discussion in 'General ME/CFS Discussion' started by Ema, Aug 9, 2018.
I am obviously several years behind on current CFS research, but when I read Health Rising’s blog The RCCX Hypothesis: Could It Help Explain Chronic Fatigue Syndrome, Fibromyalgia and Other Diseases? I couldn’t decide whether to shout for joy or break down and cry. Dr. Meglathery puts a name to a theory (albeit a complex one) that reinforces some thoughts about CFS I’ve been harboring for decades.
First, the idea of stressors and cell danger signaling. Three decades ago, when I realized something was going terribly wrong with my body, I desperately tried to explain to medical professionals what this “wrongness” was like. I explained in a way I thought they could understand, that I was certain that, for months at a time, I had survived only on Adrenalin. And then one day I woke up and my supply had dried up. I would ask them to imagine coming only inches from having your car hit by a train. Rather than fear, you feel superhuman strength and mental focus as you maneuver your vehicle out of the path of the train. It is the instant you realize you are safe that fear sets in, along with muscle-burning weakness and profound mental fatigue. Of course, we all know this is the “fight or flight response.” And that it is perfectly normal. The “wrongness” begins when you have the “near-miss” physical experience again and again, and for no apparent reason, and the weakness and fatigue last for weeks, not seconds. My attempt at describing my symptoms never worked. I was inevitably told that I must be suffering from an anxiety/panic disorder and should see a psychiatrist. But anxiety and panic do not put you in bed for weeks, and physically exhausted for months. There had to be something more going on. But what? Nobody knew.
In the 90’s I began to wonder if there was a sociological cause for my symptoms. About that time, we began to see an increase in autoimmune disorders. The medical establishment claimed that it wasn’t an increase in chronic illness, but an increase in their ability to diagnose it. But it was also in the 1990’s that the corporate culture changed dramatically. Eighty to 120 hour work weeks suddenly became the norm for ambitious young professionals, fresh out of grad school, who wanted to climb the corporate ladder. This new business model quickly spread across the country, along with the corporation-encouraged myth that working to the point of exhaustion was a badge of honor. This change in the norm, was particularly hard on working women. So, to counter negativity and encourage productivity, corporations spent millions on classes for women that focused on the myth that they could have it all—a lucrative professional career along with a husband, family, and a house in the Hamptons. Corporations began offering on-premises child-care, dry cleaning, take-out restaurants, and “minute” clinics—to ensure they got longer and longer hours from their female employees. These services were sold as employee benefits, when in truth they benefited only the pocketbooks of employers. The toxic effect of this sociological swing was that employees were rewarded for pushing themselves past their physical and mental capabilities—the result being a bunch of sick people being treated for stress-related physical and mental disorders.
Though, no doubt there are a few individuals, who thrive in a environment defined by stress, the majority of the working population, most especially the carriers of CYP31A2 mutations, become overwhelmed. This group develops either a stress ‘switch,’ where symptoms are not experienced until a certain threshold is reached,” or “an exaggerated stress response...(that) likely creates PTSD wiring in the brain, with dysautomanis and elevated danger responses over time (Remy, 2018).
Dr. Robert Naviaux’s work on Cell Danger Response fits neatly into Meglathery’s RCCX mutation theory, especially the hypothesis that, during prolonged stress (such as the corporate culture described above), a chronically stressed individual with a CYP21A2 mutation will enter into a vicious cycle of high cortisol levels followed by a lowering of basal cortisol until “overwhelm” occurs—causing an increase of Cortisol Releasing Hormone with all the negative physical symptoms and intolerances increased CRH implies. (Hopefully, I got that right...if not, forgive a novice).
One would need a post graduate degree in chemistry to truly understand these brand new theories. But so many of the common denominators of CFS are addressed here, most importantly stress in all its forms—physical, emotional, infectious— that the study deserves our attention and support.
My posts are far too long, but there is so much in this study to digest. From here I hope to read all the other posts in the forum on this study, so I can better understand the studies potential efficacy long-term. But I am excited about the human genome study and its potential to make a difference in our lives—and in the very near future.
It doesn't make sense to me. I wasn't living a stressful life before ME. I definitely didn't consider myself chronically stressed. My ME started after a tetanus booster, and most definitely involved t-cell activation, so I'll stick with the hypothesis that ME/CFS starts with immune system activation and that some feedback loop keeps it in that abnormal state.
Do you think that the tetanus booster, or your body’s reaction to it was not a “stressor”? Maybe not in the same way as a person who has been abused or neglected is stressed, or a student struggling through medical school is stressed. But definitely in the same way that a simple viral infection, for no apparent reason, can physically stress a person when his or her body becomes compromised, as a result. I’ll
be the first in line “to grasp at straws” if there is the slightest chance that that one straw will shine some light on this illness.
What I appreciate about the study is that it is not one-size-fits-all. My hope all along has been that the Human Genome Project will open doors that have, up until now, been shut tight. Our past and our future are in our DNA. The answers are there. We just need to find them.
I didn't notice any immediate effect from the booster, so it can't have been all that stressful, even for my immune system. Far less stressful than a cold virus. The hypothesis is interesting, but does it match reality (did the majority of ME/CFS victims suffer from chronic stress before developing the disorder?)? I've seen lots of hypotheses for ME/CFS that look really interesting in the fine details, but just don't seem to match reality very well.
Continuing that thought: I don't think that there is One True Cause of our disease, and it is probably a family of diseases rather that exactly one. My guess, speaking only as someone who has had it a while and met a bunch of others over the years, is that there are multiple roads in to the same condition. There are probably few roads out.
Stress is probably not a single thing. It's a useful concept to some extent, but in terms of exactly how one gets sick, not so much. Stress is a chameleon word, it means different things in different contexts, and sometimes it has a specific meaning, in other use it's conversational shorthand.
A 3rd degree burn is a stress, often fatal. Final exams are also a major stress. A large amount of either burns or final exams will .... mmmm, no. The two are not alike, we just have a common word that conveniently covers both.
She is a member here and you might want to read this thread on the topic: https://forums.phoenixrising.me/ind...dule-may-explain-overlapping-syndromes.44362/
Conflating stress and stressors is where a lot of explanations go wrong. Everything that acts on the body is a stressor ... including drinking a glass of water.
Theories like this are common. When they are specific enough, like this one is, they are testable. That means real science can be done to see if there is merit to it. This starts with investigatory studies, and when they have a candidate treatment they can start a pilot study. Most such hypotheses fail, and will continue to fail till we find the right hypotheses and test them.
Several existing ME and CFS hypotheses are similar. Some are being investigated, and a trial of the drug Cortene is underway for one of these.
I consider it viable to think of several similar diseases, or many roads to the same place, or a spectrum problem, in which case by case differ from each other only in minutia, and divisions are arbitrary. We will know only when enough science is done.
There are many post-physical-trauma categories in medicine. There is growing evidence they have the same underlying biochemistry. That will put ME and CFS in the same category as sepsis and severe burns according to current metabolomic science. ME is now also linked to African Sleeping Sickness, and Ron Davis is looking into that. So post-cancer, post-Lyme, post-sepsis, post-encephalitis and post-burns, which is only a short list of many, might have the same underlying biochemistry. We know that is probably the case with ME, sepsis and burns, but the others will be investigated in time now that we know what to look for.
I read this on Health Rising last night and I feel as though as a load has been lifted from my whole body/mind (in severe crash this week). I don’t expect cure, or help, or for these genetics to be unravelled and verified completely, for a long time.
But to have at least a dozen diseases, conditions, symptoms, that I have long suffered - related to each other, and related to one genetic module, was a relieving, validating, experience.
To connect all the different dots in one's own version of ME (and we all know that we are all different, if somehow the same) was what gave her conclusions the ring of truth, for me.
Of course I have no way of criticising her procedure, or even understanding it - but....instinct, experience, and common sense?
No doctor that I’ve come across has ever done that; or if they could, they have would never had been able to give any scientific explanation.
For ages, only fellow sufferers - i.e. people on PR - have understood what it is like to live with ME, and also to live with a medically unexplained (lol), disease.
To think that it might be medically explained has made me feel like a human being.
I believe a stressor in scientist speech is simply an environmental cause. I think it very likely that me has an enviromental cause, even if genes play a role too. The only person I can think of who doesn't seem to agree is prof edwards, who believes it may be a stochastic process in the body. Stochastic here is scientist speech for I something I don't understand.
I agree that it is “soul affirming” to see symptoms you have been told for decades are totally unrelated addressed as a group in a CFS research study—especially after years of being ignored and dismissed by the medical community
In the 1980’s I had no reason to believe that the group of symptoms I presented as an illness might be related. It was the dark ages of ME/CFS, and physicians then, like many today, had tunnel vision.
But the same group of symptoms presented two years later, and in the same sequence—and again and again over the next two decades, and always as a group. There had to be a relationship between them, no matter how improbable. So, yes, to see a study that confirms what many of us with CFS already believed to be true is worth celebrating—if only for the fact that, at last, we have some validation.
I am not a scientist, and I have the most basic understanding of biology. But I have to assume that a great deal of blood, sweat, and tears goes into all human genome research, regardless of its purpose. And even if the hypothesis is later discovered to be flawed, any discoveries made along the way will benefit the next step of the research process. So I am a little confused by negativity from a few who take issue with the direction certain CFS research is or isn’t going. Isn’t all legitimate research positive research? I respect the expertise of the forum members who have special knowledge in research and statistics. and work hard to weed out “the snake oil salesmen.” Without your help we could not begin to understand the complexities of VFS research and biology.
This may be irrelevant—but thirty years ago I was blessed with the opportunity to meet Dr. James Watson during a three-day DNA symposium. With little biology or chemistry background, I was definitely a fish out of water. But I didn’t have to understand everything Watson said to know that he and Francis Crick had done something that would change the world—-and call it intuition or Gypsy fortune telling, but somehow I knew after only a few words with this great man, that he held the key to my non-existing illness.
What I didn’t understand at first was Dr. Watson’s frustration with “the system.” He didn’t try to disguise his anger at the U.S. government for shutting down his and Francis Crick’s research for more than a decade—simply because in the 1950’s the government didn’t understand DNA and were terrified of what they didn’t understand. Can you imagine where we might be if the the close-minded men who controlled the U.S. government hadn’t stolen more than a decade of DNA research from us?
The miracle is that today Dr. Watson serves on the Scientific Advisory Board of OMF, the research group working to find the cause of CFS and other mysterious disorders. And even though Dr. Watson has gone on to develop his DNA hypothesis in ways that have changed life as we know it, I noticed while listening to one of his recent interviews, that there was the same thinly-veiled anger in his voice I had detected in 1986.
Dr. James Watson and Dr. Francis Crick (who died before the ban on DNA research was lifted) are owed much more than an apology. The U.S. government and the historically backwards NIH owe the entire world an apology.
I didn't either - no recognizable major stressors that I could tell - in fact I was something of a high...I had found my niche at my University, knew exactly what I wanted to study, was studying in a beautiful location, doing very well in school and then "it" happened - whatever it was. Hope to find out some day....
One interesting thing about the hypothesis is that it does present different roads corresponding to different assortments of those genes.
I really like the post-sepsis - sepsis-like - hypothesis.
Dr. Bell started that idea off years ago and Ron Davis and Ron Tompkins have lots of experience with it. Check out this blog for more - http://simmaronresearch.com/2018/01/chronic-fatigue-syndrome-mecfs-chronic-form-sepsis/
I interviewed Tompkins about the sepsis angle but can't post it here because it's on my website....
Thanks @Cort. I read that book when it first came out, but I forgot the post-sepsis link. The current push is because the metabolomics is nearly identical. A lot of research has been done in sepsis.
I wonder if one day we will see the label CFS change to Type 2 Sepsis?
I find the stressor argument to be very confusing. And perhaps it is not relevant to CFS studies. How is the word “stressor” defined for research purposes? Semantically, at least in the English language, the word can mean a hundred different things depending on the situation. A stressed or overwhelmed cell is not the same as a person who feels stressed and overwhelmed because she is locked in a cell. Perhaps in the interpretation of CFS research, the word “stressors” should be replaced with a term that has a more definitive and biological definition. At least for laypeople, like me.
However, I can’t help but remain curious about PWCFS who did not experience a major stressor in their lives prior to onset of symptoms. Based on my own totally unprofessional and strictly anecdotal research, I can’t come up with a single case of autoimmune disease among my limited constellation of research “participants” that’s trigger can’t be traced to a physical or emotional event.
Not that I’m suggesting that CFS is a direct result of a stressor, but perhaps, all things being equal, a major life events could tip the balance between wellness and disease without being the actual disease trigger. I also find myself questioning the research logic of including an infectious stressor (like mononucleosis) in the same category as an emotional ot physical stressor (like a divorce or a Triathlon.)
This may not make sense to anybody but me, but I’m going to post it anyway.
The problem with that definition is that it becomes so broad that it's effectively meaningless. We need a narrower definition to make it useful for predictions or analysis.
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