The causes that aren't genetic or pathogenic

[Hutan]

I couldn't think of a better title.

Of course there must be some a genetic vulnerabilities - hopefully DecodeME will find something. And of course the onset of ME/CFS seems to have something to do with infections of various pathogens.

But, all of us will have had multiple infections before the one that precipitated ME/CFS. For some of us, some of those infections will have been of the sort that are implicated in ME/CFS. So, what was it about the particular infection or the particular circumstances at the time that seems to have resulted in ME/CFS.

Or is it just random?

For example, some people are getting Long Covid on their third infection with SARS-CoV-2. Same genetics, same pathogen, different outcome. My daughter got ME/CFS after a viral infection, then recovered, and now she's had 3 Covid-19 rounds, and thankfully no return of symptoms.

Another example, I had ME/CFS for a year when I was ten, and recovered. When I was 17, I got shingles and EBV together - but I recovered quickly and easily, no ME/CFS. And then I got ME/CFS again after a viral infection when I was 47.

So, it's not just a simple equation of 'If genetics are vulnerable, and if there is an infection that causes ME/CFS, then ME/CFS'.

What other things do you think might be causing ME/CFS? What is the evidence for and against them? In my family, three of us got ME/CFS at the same time, so I have a bit of personal experience to triangulate against. I'm interested to hear your thoughts.


Over-exertion before/during the acute illness? Maybe, although I don't think that is a common factor.

Emotional stress? Again, maybe, although probably working via something like sleeplessness or smoking rate. But, I don't think it's a common factor, it wasn't for my children and I.

Hot weather or some other environmental factor like mould? I think we'd expect to see epidemics of ME/CFS, or geographic concentrations, and I don't think we have evidence of that. That said, has anyone been looking for that evidence? My children and I were in a brick house without AC for an extended heat wave, with a house full of newly delivered personal effects that had just been delivered after sitting in a container going mouldy in a tropical country, just before we got ME/CFS, so I could perhaps be persuaded about those factors.

Air pollutants e.g. sulphur compounds, pesticides. Again, for my children and I, we had those boxes of things that had been treated with methyl bromide, causing the proteins in wool and leather to react, giving off a terrible stink of volatile sulphur compounds.

What else? Medicines? Hormones?

 

[EndME]

I guess one could ask the exactly same question about MS, dementia and most other diseases. With the only answer being, we currently don't know...

Over-exertion before/during the acute illness? Maybe, although I don't think that is a common factor.

Agree, I don't think this plays much of a role. There have been acute illnesses during which I exercised and many athletes exercise during acute Covid infections and other infections (or do things like riding the Tour de France or running a marathon whilst having Covid without any long-term consequences).

Emotional stress?

Never had any, that only occurred post ME/CFS, but maybe for some it plays some minisucle and non-relevant role similar how to stress plays some miniscule and non-relevant role in autoimmune diseases even though autoimmune diseases have absolutely nothing to do with stress.

Hot weather or some other environmental factor like mould? I think we'd expect to see epidemics of ME/CFS, or geographic concentrations, and I don't think we have evidence of that. That said, has anyone been looking for that evidence? My children and I were in a brick house without AC for an extended heat wave, with a house full of newly delivered personal effects that had just been delivered after sitting in a container going mouldy in a tropical country, so I could perhaps be persuaded about those factors.

I'm not convinced by any of this, especially with thinks like ACs not existing in most countries, especially the hotter ones in Africa, South America etc. I'd be more inclined to think that ME/CFS is more common in colder countries if Vitamin D plays some miniature role, which it seemingly sometimes does in some autoimmune diseases (of course that role is not causal). If there would be good genetic studies and geographic studies, maybe something interesting would pop-up. The only thing interesting on that end to me would probably be things like the Royal Free outbreak or the Lake Tahoe outbreak.

What else?

Stochasticity!

 

[Hutan]

Stochasticity!

Well yes, and I guess chance does throw up some really odd coincidences at times. But I'm sure you can understand why I would be looking at stochasticity with a little bit more suspicion, given three family members became ill with ME/CFS at one time.

the Lake Tahoe outbreak.

Yes, I think some new investigations of the outbreaks, including the one here in NZ around Tapanui, might give us a clue.

If there would be good genetic studies and geographic studies, maybe something interesting would pop-up.

yes

 

[rvallee]

Stochasticity!

Most of the population carries H. Pylori. Most of the population never develops peptic ulcers. Similar with EBV, in some cases causing mono, in most not, in some cases leading to ME, in some cases after mono, in some cases without it, in most not.

Some people die from a falling piano and other freak accidents that require a thousand pieces to align perfectly. They had to be at the exact wrong place at the exact wrong time, doing a sequence of events where a single tiny event could have delayed their walk by a single second and they could have only been injured, or by 2 seconds and escape unscathed with the scare of their life.

Millions of people make cuts and scratches every single day. In some rare cases, the wrong bacteria get in at the wrong place and the immune system response, part of which is random based on matching antibodies to antigens in the Thymus after having being scooped up by a neutrophil (?), arrives just a tiny bit too late, or way too late, and they lose a limb, or worse.

I think that randomness is undervalued here. It's not always possible to know the cause of something, in fact human bodies not having the "shut down, pick apart, put back together, turn back on" feature means that more often than not it's not even realistic to get an accurate picture of the problem beyond the largest scale.

Why did some people who were healthy and fit drop dead from COVID in their 40s? When some centenarians got it and were barely ill with it? 4-5 times over?

Most of life is actually chance. Evolution is chance. Most natural processes are chance. It's like the weather, or Maxwell's demon. We simply cannot account for everything except in the simplest or most controlled systems. Immunity is a lot like that. It largely depends on chance, on fluid dynamics in chaotic systems and even more chance on top and underneath it, in addition to genetics, in addition to the outcome of similar past events equally dependent on chance upon chance.

I said this a few times before, but medicine needs to go through a growing phase like physics did when accepting quantum theory, which they only did at first because the math worked and it started becoming too useful to ignore. Medicine has to do that while accepting that they simply won't be able to know the cause and precise mechanism of everything ill and injury, and that they can't simply use it to argue "God did it", which psychosomatic ideology is a mere extension of.

 

[EndME]

Well yes, and I guess chance does throw up some really odd coincidences at times. But I'm sure you can understand why I would be looking at stochasticity with a little bit more suspicion, given three family members became ill with ME/CFS at one time.

Certainly, but that wouldn't make it less stochastic if the processes are purely stochastic but still involve certain things like genetics or certain exposures to get closer to some threshold. Stochasticity is more than just the flip of a coin.

But I certainly agree that it seems sensible to me that a genetic study could be launched to focus on families with a high incidence of ME/CFS and see if anything interesting can be found. Hopefully DecodeME yields something and one can take things further from there...

 

[Trish]

Yes, I think some new investigations of the outbreaks, including the one here in NZ around Tapanui, might give us a clue.

The biggest and most long lasting outbreak is Long Covid. I'm still hoping something might be found from all the research that might help shed light for the rest of us too.

 

[Mij]

There was an outbreak of EBV in my area in 1991 and 15 separate people in the same neighbourhood developed MS. I developed M.E in 1991.

 

[Kitty]

Stochasticity!

AKA luck. I agree—it might turn out that there's some fascinating combination of events that are necessary, but it seems just as likely there aren't.

 

[Kitty]

But I'm sure you can understand why I would be looking at stochasticity with a little bit more suspicion, given three family members became ill with ME/CFS at one time.

I feel the same, because there were also three of us (though not at the same time). Also, I have two close but unrelated friends that I've shared houses with, and we all developed ME (again, not at the same time).

But there three or more cases of all sorts of other things as well, in both family and friends. ME sticks out because it's unusual and devastating, whereas a family's peculiar tendency to develop lactose intolerance in middle age isn't. The endometriosis wasn't exactly a picnic, but at least we eventually saw the back of it.

 

[duncan]

I think immune tolerance will eventually be shown to play a role, but that is tied into pathogens (e.g. latent viruses). This is a theory that seems to have morphed from just pregnancy and infants being born with it.

I've been trying to get my arms around it, but having difficulty. It could apply to Covid, at least in theory.

 

[EndME]

I said this a few times before, but medicine needs to go through a growing phase like physics did when accepting quantum theory, which they only did at first because the math worked and it started becoming too useful to ignore. Medicine has to do that while accepting that they simply won't be able to know the cause and precise mechanism of everything ill and injury, and that they can't simply use it to argue "God did it", which psychosomatic ideology is a mere extension of.

As a complete outsider, I do think the discipline does somewhat try to accept this, after all medicine has never been about knowledge but much more about helping people (at least that has been my layman understanding), and that is precisely were some of these problems have arisen. Having to be solution oriented, instead of knowledge oriented, seems to have created some strange dynamics were the acceptance of incomplete knowledge doesn't always translate well into clinical practice, where the discipline is suffering from a publication bias were only positive results are publishable and pharmaceutical companies are purely run like ordinary economical companies were only positive numbers count and gaining knowledge is rather irrelevant.

And it is good that doctors never ask themselves "does something interesting happen if I were to give this person a third eye, a second heart, were to cut-off their arm and inject them with this bacterial infection" which is precisely how physicists or mathematicians work. They should be there to help.

*I wanted to note that by stochasticity I'm not referring to "true stochasticity", which only exists in philosophical thought experiments and quantum mechanics. Almost everything we describe as "stochastic" is not inherently "truely stochastic". The flip of a coin and throw of a dice are purely deterministic events, we just can't gather complete information to describe all of the involved variables and as such we model them using probabilistic ideas. That is the type of stochasticity I'm referring to.

 

[poetinsf]

You can only speak in terms of predisposing factors (of which I have multiple) rather than the causes since there are so many unknown/random variables. In my case, I can rule out pathogens as the cause with about 90% confidence. But I'd agree with Trish: Long COVID is definitely the biggest outbreak and should offer some clue. I think the novel virus uniquely put strain on human immune system causing the huge outbreak of ME/CFS. I suspect innate immunity in particular, obviously because that's what gets into over-drive against a new pathogen. That is probably what gets strained in cases of OTS as well, which was the genesis of my MECFS, since it is responsible for clean-ups and repairs.

 

[JemPD]

Well yes, and I guess chance does throw up some really odd coincidences at times. But I'm sure you can understand why I would be looking at stochasticity with a little bit more suspicion, given three family members became ill with ME/CFS at one time.

I feel the same, because there were also three of us (though not at the same time). Also, I have two close but unrelated friends that I've shared houses with, and we all developed ME (again, not at the same time).

Hysteria? Surely just talking about being ill amongst yourselves is what caused you all to get it, like George Monbiot spreading long covid by talking about it?

Perhaps you were living in a 'hysterical house'
or one with a 'conversion conker tree' in the garden that infected you all?
Or maybe exposure to 'Functional fungus' was the culprit? Eating with 'Psychosomatic Spoons'?



Sorry i know that joke was in bad taste but i couldnt resist it, its so frustrating that these things havent been studied more. All that money wasted researching bull sh*t theories about hysteria, or any of the other more modern names for it. It may well be random luck etc, but its hard not to look for patterns... its instinctive and yeesh if we could spend some money looking into it we might find something. Its intriguing for sure.

Edit: for those who wonder what on earth im on about with the 'conversion conker tree' etc, pls see the jokey/fun thread Members only - Pompous parsnip - a silly word game - adjective and noun with no obvious connection | Page 5 | Science for ME (s4me.info)

edited for sense

 

[Kitty]

Or maybe exposure to 'Functional fungal spores' was the culprit? 'Psychosomatic Spoons'

You should definitely enter functional fungus and psychosomatic spoons for a prize in the Pompous Parsnips thread.

 

[JemPD]

You should definitely enter functional fungus and psychosomatic spoons for a prize in the Pompous Parsnips thread.

lol i just realised 'fungal spores' is 2 nouns, have edited to functional fungus, which is what i meant. Have edited

Sorry totally off topic. Anyone not a member or not read the pompous parsnip thread its a silly word game we have been playing to bring us some much needed laughs

 

[Jonathan Edwards]

I wanted to note that by stochasticity I'm not referring to "true stochasticity", which only exists in philosophical thought experiments and quantum mechanics. Almost everything we describe as "stochastic" is not inherently "truely stochastic".

I am not so sure. I have recently uploaded an article to the journal Qeios on the basis of what people call free will and discussed fundamental stochasticity there. It is actually entailed logically by the continuous nature of the spacetime metric, the discreteness of events and the impossibility of infinite precision - as understood by Leibniz in 1700 although he never quite explained why he understood, just said it must be so.

Quantum theory reflects this and since everything is quantum everything is truly stochastic to a degree. The more practical side of things is that in the fluid phase of biological systems at the chemical level the fundamental stochasticity dominates - so all chemical dynamics in that environment are statistical. The slight indeterminacy of every event, with events taking femtoseconds, very rapidly makes everything random.

The interesting thing is that biological systems have evolved to manipulate true randomness in clever ways. The one I got used to is the re-arrangement of immunoglobulin genes to form individual antibody species using DNA breakage and repair. So autoimmune diseases are likely to occur in a given individual at a particular time in part due directly to a truly stochastic process, with mass positive feedback amplification.

 

[rvallee]

As a complete outsider, I do think the discipline does somewhat try to accept this

Somewhat, unfortunately leaves out a lot of space, like the entirety of psychosomatic ideology. Basically, they accept it, except where they don't, and where they don't want to, they do the exact opposite of what needs to be done. I guess that's the real problem, that it's not enough to accept it when it's convenient and ignore it when it's not, but to universalize the implications of what it all means, that even in many cases where they could do something if they only knew, they won't always be able to know, there is a fundamental, nearly universal, uncertainty principle in the way.

It could be argued that this is what biopsychosocial medicine is about, where not understanding what the problem is, the best they can do is help in whatever ways they can, but it has long been extended into "there isn't even a problem, none will ever be found, and there is no point bothering to look for one". That's just the opposite and wrong on every level.

That's usually how those problems go. It's like liars, even serial liars don't lie all the time, just precisely where it is most convenient to them. But it should be treated more like murder. It's not possible to be 99% not a murderer. It's a 100% or 0% thing. Just like science is also an all-or-nothing, defaulting to some religious system or a mythical quackery from the 19th century isn't acceptable sometimes, it just never is.

 

[rvallee]

I think the novel virus uniquely put strain on human immune system causing the huge outbreak of ME/CFS

Most of the pathogens we come in contact with, it's the first time we ever encountered them. There are so many out there. Trillions and trillions and combinations and permutations among many of those we regularly come into contact with. I don't think that's especially relevant. It's too easy a cop-out.

 

[EndME]

I am not so sure. I have recently uploaded an article to the journal Qeios on the basis of what people call free will and discussed fundamental stochasticity there. It is actually entailed logically by the continuous nature of the spacetime metric, the discreteness of events and the impossibility of infinite precision - as understood by Leibniz in 1700 although he never quite explained why he understood, just said it must be so.

I read this work by Leibniz back when I was studying philosophy but I cannot remember any of it and my brain is certainly not functioning well enough to be able to understand any of it anymore. I tried reading your text on Qeios but quickly had to admit that I’m not made out for those things anymore and as soon as I saw the term condensed matter I anyways knew I had to resign.

I did attend a talk by Roger Penrose a couple of years ago on conciousness and quantum mechanics in relation to neuroscience and anaesthesia. He seemed rather convinced of the ideas and I would trust his word on anything, but his angle seemed rather different, focused on the quantum mechanics of it all and had nothing to do with inherent notions of Minkowski spaces, infinite divisibility, uncertainty principle and the like, at least as far as I can remember.

Quantum theory reflects this and since everything is quantum everything is truly stochastic to a degree.

My extremely basic understanding had always been that at those levels wave functions have long since collapsed and you're left in a rather deterministic world, which we describe in a probabilistic language, where any particles that used too have long since spun (Penrose argued that it is precisely that collapse that gives rise to consciousness rather than the opposite, but what that exactly is supposed to mean is beyond me). I think the question would be what “to a degree” means and at what degree do are we making the observations. How much "true stochasticity" is left, if any?

The more practical side of things is that in the fluid phase of biological systems at the chemical level the fundamental stochasticity dominates - so all chemical dynamics in that environment are statistical. The slight indeterminacy of every event, with events taking femtoseconds, very rapidly makes everything random.

Wouldn’t this just be a possibly infinite amount of dice all rolling at the same time and interacting with each other creating random phenomena, that however have nothing to do with “true stochasticity”? Of course there may be underlying events that are “truely stochastic” but at that level of interaction is any of that left?

In the limited time I had the opportunity to work as probability theorist, I never came across any "true stochasticity".

 

[Hutan]

The interesting thing is that biological systems have evolved to manipulate true randomness in clever ways. The one I got used to is the re-arrangement of immunoglobulin genes to form individual antibody species using DNA breakage and repair. So autoimmune diseases are likely to occur in a given individual at a particular time in part due directly to a truly stochastic process, with mass positive feedback amplification.

Yeah, but presumably there are processes in some individuals that fix a system that went awry due to some random chance. Why not in everyone?

I accept that things happen just by chance, but I reckon there's a risk of replacing psychosomaticism with stochasticism - a sort of the 'god of the gaps' shrug of the shoulders. For sure stochasticism is preferable to psychosomaticism, at least there is no blaming going on. But I like answers, as do we all. And sometimes there will be an answer if it is looked for hard enough.