frozenborderline
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Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of, and finding treatments for, complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia, long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.
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i found this theory, which is very complicated, and I can barely begin to understand, that seeks to explain underlying genetic causes for CFS and overlapping illnesses
@Learner1 @Hip @pattismith @Iritu1021 I don't know if you guys have all seen this
Yes, I have investigated Meglathery and her RCCX theory. She seems to be very devoted to it, having put a lot of effort into it.From your link:
If you are not familiar with the theory, on first blush, you may be skeptical as the RCCX Theory defies many common myths which are still widely held by patients and doctors alike.
Yes, I have investigated Meglathery and her RCCX theory. She seems to be very devoted to it, having put a lot of effort into it.
I think I fall into the skeptical category. I don't know what myths she is talking about and tend to prefer things that can be identified and measured to verify any theory, which seems impossible from what I've read with this one.
I don't know if the theory is correct or not, but the issues I have are:
ME/CFS is indeed a complex disease. The scientists believe causes are heterogeneous and that there are subsets. There likely is a subset with some of the qualities Meglathery describes. The scientists have already been finding SNPs that seem to cluster in ME/CFS patients, none of which seem to be the same as those on Meglathery's list.
- She is a psychiatrist and I don't believe in what psychiatrists do, having learned that most mental illness is do to food allergies, leaky gut, nutrient deficiencies, infections, inflammation, toxicity, and very occasionally and less commonly some awful SNP or SNPs.
- She is not providing rs numbers that anyone can check, either on 23andme, WES, etc. She just goes on and on and on about these genes, which everyone has. Which SNPs are they and what role does each one have in this? How do you know if they are doing it?
- Genes can express differently based on environmental factors and how other genes are expressing themselves. Just because one has a pathological SNP, in many cases, it's not expressed until tje right environmental factors are there.
- Sure they can create many of the symptoms she refers to, but I have found it's more productive to look at what's going on biochemically or perhaps with physics, and to try to "normalize" whatever is out of whack, using a systems point of view, with a combination of supplements, pharmaceuticals, hormones, stress reduction, and techniques that affect the physics (acupuncture, trigger points, and other modalities).
- If she is correct, this may apply to some of us, but likely not to most of us, as she herself admits.
- Then there is the question, if one can figure out that all this applies, what does one do about it? After reading and reading and reading, I don't see a thoughtful, comprehensive, treatment approach that will get anyone anywhere. Mindfulness is wonderful, but what she is describing is going to take more than mindfulness to fix.
My own journey has brought me a long way with personalized medicine. It's been by necessity, because there just isn't enough research out there to nail the perfect ME/CFS theory and I don't have years to wait for perfection. I've also found that I have some SNPs (HFE, Factor 2, SOD2, and many more) and environmental factors (carboplatin and paclitaxel) likely not shared by others and on top of all the usual ME/CFS factors that have confounded my situation, so that unique treatment components must be personalized. Each one of us will have unique factors as well.
So, while theories are interesting, the way to get well is to normalize the body's biochemistry and physics. Theories can help us, but there is no substitute for high quality lab work and other testing
and a prioritized, personalized, systematic treatment plan, which unfortunately is no easy task.
Thanks for sharing @debored13 - I appreciate your continued quest to bring in interesting ideas and move the dialog along.
The CYP21A2 mutation contains an evolutionary switch which is flipped as the person desperately tries to make enough cortisol to handle the stress, triggering 21 hydroxylase overwhelm and then possibly stress induced mitochondrial shutdown.
Dauer-like response or stress-induced mitochondrial shutdown has very recently been discovered in patients with severe CFS/ME by Ron Davis PhD and Robert Naviaux MD PhD (initially described by Naviaux).
The symptoms which occur after 21 hydroxylase is overwhelmed are the same, independent of the trigger. For more information about this, please see RCCX Theory Part I.
Mutations [in CYP21A2] result in an exaggerated stress response (high acute stress response cortisol), low basal cortisol and elevated CRH (corticotropin releasing hormone, aka CRF) which directly turns on the immune system and inflammation.
I wrote about the RCCX theory in a blog for Health Rising.
- The autoimmune conditions that can be affected by the RCCX gene cluster
- The pros and cons of RCCX
- The link between complex chronic illness and hypermobility
- The evolutionary tradeoff of genius and illness
- The unorthodox way to identify if you have RCCX gene cluster issues
- Michael’s theory about the RCCX gene cluster and the stress response system (HPA axis)
- How the RCCX gene region is affected by retroviruses
- How the lymphatic system is connected to RCCX
- How each gene mutation has its own benefits and drawback
- The connection between the Cell Danger Response (CDR) and the RCCX gene cluster
Copy number variation gene sequence is only comprised something like 4.5% to 9% of human genetics, which is not a huge percent but we know that copy number variations are strongly associated to a lot of different disease processes, especially chronic disease processes, complex diseases.
Certain people that have certain RCCX genotypes, they are often brilliant. They often have a genius intellect and emotional intelligence and are highly in tune with different emotional parts of themselves.
I would even argue that there are spiritually advanced individuals in some cases but they have … often, they have a preponderance of chronic disease and an intolerance to stress and they may border on mental illness or have full-blown schizophrenia or bipolar disorder so it’s two sides of the coin.
Currently as it is at this time, there’s only a very small handful of labs in the world that are capable of sequencing the RCCX gene region. You can’t go to 23andMe and get this cluster sequenced. You can’t walk into LabCorp or Quest Diagnostics to get it sequenced either.
The gene region on chromosome 6 that RCCX is found in is known as the MHC region or the HLA MHC set of genes. It’s said to have what’s called a very long linkage disequilibrium which basically means that this is a really, really, really complicated part of our human genetics that is involved in immune response and immune signaling and inflammation and it’s just a whole parade of complex genes that have so much different variability and RCCX is literally right smack in the middle of this complex thing.
We’re dealing with a very complex gene cluster in the middle of arguably the most complex part of the human genome.
The RCCX gene cluster contains in it two retroviral elements. One of the retroviruses is known as HERV-K and HERV-K is actually situated within the complement C4 gene in the cluster.
Retroviruses play important protective roles in how the immune system is supposed to behave. What the research suggests is that if we don’t have enough of these HERV-K retroviruses in the C4 genes, we don’t have adequate protection.
It was not easy! I went through three drafts of that paper (the longest was nearly 8 pages single spaced!) before we got to the final one that Dr Meglathery and I both liked.Glad that you were able to understand the essence of the theory, Ema! My brain is struggling!
What's strange to me is that she completely omits the role of thyroid hormone in this. As a psychiatrist, she should know that it's an effective treatment that's shared both in people with bipolarity and CFS/POTS - three conditions that she correctly linked together. Although I guess the new generation of psychiatrists are no longer using thyroid hormone after the big pharma intervened with more expensive and less effective drugs.
Also, she talks about copper and berberine as something she tried with mixed results and attributes their effect to steroid synthesis. However, berberine is a 5HT1A receptor agonist (similar to T3) and copper is involved in dopamine synthesis (which explains why she initially felt better on it and then felt worse - similar to what happens for most of us when we take stimulants).
@debored13,
T3 clearly does something for CFS - and you've experienced it for yourself. But T3 is not a solution on its own.
I'm now pretty much back up and running back at my pre-crash level thanks to a well-calibrated combo of lithium orotate and levothyroxine (took a lot of faith into what I was doing to get to this point). While this may not work for everyone, I doubt that I'm a total outlier as I was diagnosed with a "classic CFS" and POTS by some very respectable specialists in those conditions (who either did nothing for me but waste my time or made me feel a lot worse). Also, mine is not some accidental recovery - if I stop what I'm taking I begin to slide back right to where I was.
The treatment I use is the classic "old school" psychiatry treatment with the only exception that I use lithium orotate instead of lithium carbonate. Lithium orotate is much more bioavailable for the brain and doesn't require toxic doses. I no longer use any exogenous T3 because I've realized that given the specifics of my CNS, it destabilizes my neurons, especially in higher dose or with prolonged use, or when combined with other stimulating drugs.
In addition, I now understand how to regulate the conversion (again lots of trial and error there - see "Peripheral Deiodination Table" I've compiled). It is much better to allow the cells do the work at their own pace than to bombard them with external T3 (which when used this way is less of a hormone and more of a stimulant).
Lithium plays a huge part in my CNS T4 conversion. I need enough levothyroxine to be able to tolerate lithium. If I were to use either one of these drugs without the other, this method wouldn't work.
Everybody is chasing something that will make them better the same day. The reality of treating CNS disorders is that it doesn't work like that. I have benefited hugely when I began reading more about psychiatry than about CFS - and the message I derived from there is that it takes time, patience and the willingness to tolerate initial side effects while the body re-adjusts before one can get better.
Complex theories may be interesting but treatments that work is what we should really care about.
I did have a reaction to thyroid that was initially positive enough that I'm convinced it's "the thing" to an extent, but it's so tricky. And even if I treat it, i'm not sure that it will entirely treat my CFS, there are patients who are on thyroid replacement and still sick. Metabolism seems very complicated, and mine is severely broken, albeit with totally normal blood levels of thyroid.
Michael McEvoy has written some great stuff on RCCX but he has gone off in some directions of his own, as one does, after learning about this complex from Dr Meglathery. She doesn’t support all of the conclusions he draws
anyway, i agree with @Hip that the part in RCCX theory about predispositions and personality, negative traits and gifts, was interesting. The biopsychosocial people and the backlash to that psychosomatic model of CFS has probably made it less in vogue to talk about stress and trauma, even though those are complex physiological phenomena, not just in your head, and predispositions to these could be important in looking for etiology, genes, etc.
I know pre-illness I was "healthy" but not that healthy... Obviously I can't even compare the mental illness and stress I had then to the awful level of impairment I have now, but I certainly was not good at handling stress, I'll put it that way. It wasn't "just" stress that caused my illness but I wonder about the genetic components to handling stress.
But I like Dr Sharon Meglathery's approach, and I much appreciate it when a psychologist brings in biology to the picture, and tries to understand personality characteristics in terms of what goes on in the physical brain and body.
Yes, the backlash against the psychosomatic/biopsychosocial model of ME/CFS was, and is, necessary, because this model resulted in much of the medical profession viewing ME/CFS as a purely "all in the mind" condition, which then led to inappropriate psychological treatment, and sometimes abuse of especially young ME/CFS patients.