Publications that show ME is biological

Jonathan Edwards said:
I personally think it very likely that the primary problem in ME is a signalling one in either immune or nervous system or both.
Click to expand...

That idea is interesting but I cannot understand how faulty signalling can be the primary problem in the fluctuating, regularly relapsing and remitting, stage that many experience. Does there not need to be something even more fundamental to cause the fluctuations in the signalling?
 
chrisb said:
That idea is interesting but I cannot understand how faulty signalling can be the primary problem in the fluctuating, regularly relapsing and remitting, stage that many experience. Does there not need to be something even more fundamental to cause the fluctuations in the signalling?
Click to expand...

Actually, I think the relapsing/remitting aspect is in favour of a metastable state of a complex re-entrant signalling system - the main candidates being immune system and brain. Autoimmune diseases arise from faulty feedback in signalling cells that arises at random and can fluctuate wildly over time.
 
Jonathan Edwards said:
I think there is a reasonable chance that there is a key signal that could be corrected or blocked.
Click to expand...

I don't pretend to understand how this would work biologically, but this sounds like you are saying it's something central rather than localised in muscles, blood cells etc.

How can this explain localised effects in muscles? For example, whichever muscle group I over-use becomes more painful and weaker for hours or days afterwards?
 
Jonathan Edwards said:
I personally think it very likely that the primary problem in ME is a signalling one in either immune or nervous system or both. Symptoms are downstream of that. The same signalling problem could affect CPET results I think, through various mechanisms - which makes the CPET result a downstream by-product. It may be real but it does discriminate ultimate causes.
Click to expand...

I don't understand your reasonning here. Whatever the problem (signaling or not) the CPET tests suggest that there is a problem that is not malingering, nor deconditioning, but has a biological reality.

Jonathan Edwards said:
In the longer terms various thoughts leading to patterns of behaviour can change all sorts of bodily functions.
Click to expand...

I understand that you're challenging results to be sure they're reliable, but I think you're maybe going a bit too far. Is there any proof that "thoughts" or mental stress can have any impact on that type of tests?
 
Cheshire said:
I understand that you're challenging results to be sure they're reliable, but I think you're maybe going a bit too far. Is there any proof that "thoughts" or mental stress can have any impact on that type of tests?
Click to expand...
Suppose you consider something like a panic attack. Now I'm one of the most laid-back people you will meet, but I remember being in the shower a few years back, and the postman came with a registered letter to do with my brother-in-law's estate. My wife signed for it, but I remember suddenly my heart was pounding like mad, feeling dizzy, in turmoil etc. There was no particular reason - I was a joint executor with a solicitor, and it was all pretty straightforward.

Now were the very real effects of my (mild) panic attack down to a mental response, or to a physical condition? I guess it would be really hard to sort out the borders there – do I have a chemical imbalance that now makes me more sensitive? Or had my illness changed my mental state? Just because an effect is clearly physical doesn't make it easy to get behind it and decide what the trigger is.

Now for the even more weird part, that was my one panic attack. I haven't had one before, and haven't since.

So, back to muscles, do they ache after a minimum amount of exercise because of some physical imbalance, because they have not been used for more than a certain amount, or because my mental state sends my physical system out of kilter when I do exercise? Do I have a similar kind of mental panic reaction when threatened with exercise, that affects the way that my muscles respond?

As you know, I am quite sure that it isn't my mental state or that I am out of condition, but that's not the same as being able to prove it. The psychs that believe ME is psychological (and remember that there are very many who do not) have been unable to show that they are right, and they have had the bigger share of research funding, so that is one argument that tilts the balance in our favour, but that's all it is. Until there is a clear-cut biomedical finding (as opposed to groups of different spreads of abnormalities), we can only argue in terms of a balance of likelihoods.

In fact, I don't think the psychs have ever really bothered much about trying to show the cause is psychological. Like a fervent fundamental religious adherent, they know they are right: it is clear from the way that the PACE trial was set up that all they intended to do was to determine whether CBT or GET was the better or the most cost-effective treatment.

But this balance is important when we are considering something like GET, which shows no advantages, and where the biomedical understanding suggests harm.
 
Graham said:
Do I have a similar kind of mental panic reaction when threatened with exercise, that affects the way that my muscles respond
Click to expand...
Shouldn't you have the according thoughts and feelings then?

I still do light training. I know I don't feel great during and after it. Still, I have a passion for activity (training), and I am convinced activity (exercise...) is important - if you're healthy. I know that with ME I'm probably acting irresponsible. I admit I can't stop it completely.
Now I don't know what would be the outcome of a 2 day CPET test in my case. I can say that I don't feel fear; I just hope I can train as much as possible. I do know that after such a "training" day my capacity is reduced.

We all experience the play between mentality (thoughts, emotions) and physical reactions. But the question is the same as about psychological diseases: Does this lead to biochemical changes that cause illness or pathological processes? Up until now there is no "yes" to this. So the question is if a mental state (fear of exercise e.g.) can lead to those substantial changes that were observed during and after the CPET in ME.

By the way: Every participant must have the same or similar fear quality and quantity in order to produce the same or similar biochemical processes observed in the 2 day CPET study. I think that's very unlikely.

In total, I don't think that a certain mental state can be made responsible for the outcomes that were observed in the CPET study.

But probably I don't understand the argument?

I have made one observation though: My impression is that my body reacts stronger to mental/emotional things (e.g. excitement) than in the past. For instance, in the past excitement would lead to a faster pulse. Today I have the same, but I also feel breathless. So perhaps the pathological processes in ME also lead to an increased physical reaction to mental/emotional input.
 
Cheshire said:
I don't understand your reasonning here. Whatever the problem (signaling or not) the CPET tests suggest that there is a problem that is not malingering, nor deconditioning, but has a biological reality.

I understand that you're challenging results to be sure they're reliable, but I think you're maybe going a bit too far. Is there any proof that "thoughts" or mental stress can have any impact on that type of tests?
Click to expand...

I am deliberately being the devil's advocate here but I think it is important to do that because some people are I think making too simple an interpretation of these results.

Whatever the problem is it is a biological reality but thoughts are biological realities too. Effects of thoughts are biological realities. The argument we need is more subtle.

Try this for a thought affecting a result: a normal person in Richard Edwards's lab does a CPET and then is told to do step down exercises repeatedly for two hours. They have the thought that they should do these exercises to help the researchers and as a result do them. The step down exercises cause macrophage infiltration in the quadriceps overnight (an effect Edwards's group demonstrated) and a CPET the next day is less good - anaerobic threshold has changed. (I don't know if this happens in this particular context but I think it is entirely plausible.)

So a thought affected the CPET result. The thought is entirely a biological reality and entirely physiological but it is a thought. Moreover, there was nothing wrong with the person. They just did something that affected the test in an unusual way.
 
Jonathan Edwards said:
So a thought affected the CPET result. The thought is entirely a biological reality and entirely physiological but it is a thought.
Click to expand...
Surely you can't conclude that the thought was any more than peripherally relevant, in the way that eg, having legs is relevant for the test to occur, without testing to see whether a similar group that have the thought but are then told after all not to do the exercise have the same CPET result, and whether a different thought (I'll do this for the participation payment, supposing there was one) results in a different test result.
 
Jonathan Edwards said:
Try this for a thought affecting a result: a normal person in Richard Edwards's lab does a CPET and then is told to do step down exercises repeatedly for two hours. They have the thought that they should do these exercises to help the researchers and as a result do them. The step down exercises cause macrophage infiltration in the quadriceps overnight (an effect Edwards's group demonstrated) and a CPET the next day is less good - anaerobic threshold has changed. (I don't know if this happens in this particular context but I think it is entirely plausible.)
Click to expand...

The CPET isn't substantially less good, on average at least. If someone exercises for two hours, then perhaps yes. The typical CPET takes 2-15 minutes.
 
Graham said:
It's more like a religion than a science: any effort to "disprove" that there is a God is ignored, because believers "know" it is true.
Click to expand...
I remember a lifetime ago (almost) when us RAF apprentices had to go to a sort of "Sunday school" (cannot recall what it was called now), and someone asking "What if an all powerful being turned up who proved to be even more powerful than God?" The answer given by the vicar was along the lines of "Well if this being truly did prove to be more powerful, then it would obviously be the true God instead." Really did bring home the distinction between preaching and teaching.
 
On the theory that PACE had no participants who were frightened of exercise because these people would not sign up (and that therefore PACE did not test the theory of exercise-phobia as a cause of ME):

I don't think this idea works. I might be terrified of flying because the plane might crash and I would die a horrible death. Despite that, I might be willing to sign up to a program that will cure me of my phobia and allow me to travel by plane. Lots of people do. That is because they rationally know that the vast majority of the time, people get on a plane and get safely to where they are going. And that it is just that when they get on a plane, they can't think rationally.

Similarly, I might be frightened of exercising because I think I will feel a lot worse after it. But if everyone around me is saying, 'you might feel bad initially, but if you push through it, you will recover', and I see people with other illnesses using exercise to rehabilitate, and I really want to recover, then I might sign up for the PACE trial to help me get over my "irrational fear".

So, if there were chronically fatigued people with a fear of exercise, then I think they could have been recruited.
 
On a person's state of mind affecting the 2-day CPET result:
I was slightly apprehensive about the first test. I had heard that it is quite difficult, and there was the wearing of a mask, getting the mouthpiece in... But, the people were nice, it was only 7 or 8 minutes of cycling and it wasn't bad at all. So, for the second test, I was much more relaxed. But the second test showed that I hit the anaerobic threshold much more quickly and at a lower work rate i.e. a typical ME result. I imagine some people were like me, more relaxed on the second test - and some were less relaxed.

I'm not understanding why the abnormal 2- day CPET should be dismissed on the grounds of some possible confounding impact of thought or mood. Presumably healthy people doing the CPET might also have a range of thoughts or moods - and yet healthy (even sedentary) people seem to be able to produce consistent results over the two tests (as do people with the other illnesses tested so far).

The CPET results and initial findings to do with cell respiration seem to hang together. I'd like more evidence about how abnormal thinking or behaviour might produce abnormal CPET results before they are waved away as not evidence of an underlying biological problem.
 
Hutan said:
On the theory that PACE had no participants who were frightened of exercise because these people would not sign up (and that therefore PACE did not test the theory of exercise-phobia as a cause of ME):
Click to expand...

I think that is fair argument @Hutan. However, I think there are subtle differences between phobia desensitisation therapy and CBT. Phobia sensitisation is something that anyone is supposed to be able to do just by exposing the patient to their bogeyman. I did phobia therapy as a student with no training other than this. CBT, according to Wessely and Chalder, requires skilled 'cognitive strategies'. The whole point of having professors of CBT is that it is a special skill that cannot be delivered by anyone (as the nurses in the FINE trial found).

I also think there is quite a big difference between fear of flying and the proposed false beliefs about exercise they propose. It is complicated but it seems to me the reality will include two situations. One is people who have genuinely come to believe exercise does them hear, unlike the flying phobic who realises there fear is irrational. The other group will be people who have felt bad sufficiently often after exercise to have evidence for it being bad. They might try 'pushing through' again but I strongly suspect most will have already tried it and failed.

I concede that the argument that not absolutely nobody with the false beliefs about exercise CBT is intended to cure would have volunteered. On the other hand I still think the likelihood is that a high proportion of people with beliefs about exercise being bad would not have volunteered. After all. it seems that a huge number of people identified as candidates turned the trial down, and this is likely to have been one of the chief reasons.
 
The first test was in the morning of day 1. I felt pretty good after the test and good all afternoon. In the evening/ night, I had maybe 5 hours of feeling awful - the usual PEM: exhaustion, chills, sore throat, burning feet, crushing pain, unable to sleep. But the next day, I was ok.

This was a 48 hour retest. So I was retested on the morning of day 3.

I still haven't really worked out how PEM works - what factors influence how soon PEM happens and how long it lasts. I don't know why I got PEM so quickly on day 1, unless it was the impact of the travel (including preparing the house for my teenage son to survive on his own, packing and a plane flight) on day 0.

I didn't feel the CPET test was very hard. 8 minutes cycling, with only some of it hard cycling, was easier than a trip to the supermarket for example. Having done the test, I understand that there might be factors that aren't controlled such as how much activity is done outside of the tests. I know there should be more replication.

But, my day 3 test was substantially worse. I went from average to good for my age on the measures to poor to very poor. The measure of effort showed I did my best.

If that is very often found in people with ME and if that is not a common finding in healthy sedentary people, then it seems to me to be a clue.

(Hopefully I answered your question somewhere in there).
 
Last edited:
Hutan said:
The first test was in the morning of day 1. I felt pretty good after the test and good all afternoon. In the evening/ night, I had maybe 5 hours of feeling awful - the usual PEM: exhaustion, chills, sore throat, burning feet, crushing pain, unable to sleep. But the next day, I was ok.
Click to expand...

OK, so in a way this was a trick question, but in good faith.
Various people, including Willy Weir and the MEA purple book interpret the deteriorated result on the second CPET as 'an objective demonstration of PEM'. I strongly suspect that van Ness and Keller tend to think something like that too. But your PEM was over and done with. You might have had PEM again after the second test but by all accounts during the second test you did not have PEM.

If anything it looks as if the symptoms of PEM may be caused by some process that as a later knock on effect reduces anaerobic threshold. That is of course very consistent with an organic process involving immune system or nervous system or both.

I very much go with go with that way of looking at things but I think this illustrates the danger of saying 'Ah well, the 2-day CPET gives definite objective evidence the PEM is real'. It shows that some biological effect is definitely going on (assuming the methodology was reliable) but we are still left with all sorts of vaguely possible alternatives routes to that, including ones that may be dependent on thoughts, either recent or in the distant past. I am just warning people against claiming cast iron proof of this or that when science is so often more of a grey area.
 
You must log in or register to reply here.
Back
Top Bottom