That's true, but ME may not involve significantly abnormal levels of anything; it could be an abnormal response to normal levels. I've also suggested that it could be a set of some number of factors that are only slightly off-average, but each factor is off in the same direction, and their effects add up. How do we ask researchers to check their existing data for such correlations?
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Using deconditioned people as controls
- Thread starter forestglip
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Yann04
Senior Member (Voting Rights)
More research funding will surely get us more data that we crucially need. And the rise of statistical analysis using more sophisticated regression or other machine learning techniques will help find these kinds of abnormalities. However, as this thread discusses, I would be concerned such abnormalities would be pointing to deconditioning more than anything.
I never looked too deep into it but the “Ramen spectroscopy” pilot study of a diagnosis test found something of the sort i believe.
I'm not 100% sure what you mean by abnormal response, but presumably even that would theoretically produce a biomarker. Whether an altered set of genes, an altered brain region, I don't know. But if the body is doing something different, then something in the body is chemically different. And using severe patients should provide the greatest chance of noticing it. Whether it's levels of leukocytes in the blood, or copies of a problem gene.
Same with multiple factors. It might be harder, and might not be possible to find even with severe patients, but at least that would give us a better shot.
Yann04
Senior Member (Voting Rights)
I don’t personally understand this well myself, but I think it’s important to distinguish between a biomarker and biological abnormalities. Because as far as I know we have consistent findings of a couple of biological abnormalities, such as in T-cells.
I might not be using the terminology correctly. Abnormality may be what I mean to say.
Yann04
Senior Member (Voting Rights)
I would guess that biomarker is something unique to the disease that consistently differentiates between that disease and healthy people/people with other diseases.
A biological abnormality might be more of an “abnormality” found on “average” in patients, ie. the average patient has a larger region of the brain compared to controls, but this comes out when making averages, not accurate enough to say if an individual has the disease or not. Or something that is not “normal” but present in various diseases (such as T-cell dysregulation) so it doesn’t properly differentiate one disease from another.
I am not educated in medicine so take that with some salt, thats just how I understand it.
A biological abnormality might be more of an “abnormality” found on “average” in patients, ie. the average patient has a larger region of the brain compared to controls, but this comes out when making averages, not accurate enough to say if an individual has the disease or not. Or something that is not “normal” but present in various diseases (such as T-cell dysregulation) so it doesn’t properly differentiate one disease from another.
I am not educated in medicine so take that with some salt, thats just how I understand it.
A brain cell produces certain outputs for given inputs. That can be modeled as a mathematical equation: IF input A>.6 AND B<1.8 AND C>2.3 THEN trigger output pulse. Some other factor in the brain can change that equation, resulting in an output pulse maybe when C>.13. The inputs remain the same, so no biomarker there, but the response to those normal inputs is different. The result to the person might be hypersensitivity to inputs, or changes in body functions. The change in the cell might be too subtle or hard to measure to be a biomarker.
As an example of the complexity of glial interactions with neurons, have a look at https://www.nature.com/articles/4402144 I only skimmed it (it's very technical), but it shows that there are a lot of complex interactions affecting how neurons work. It's easy to imagine just one of those factors being slightly abnormal result in brainfog, malaise, etc.
That paper surprised me with the importance of glial cells to human intelligence. Human brains have a large difference between glial/neuron ratios and varieties compared to mouse brains. If ME isn't common in non-humans, maybe this is why.
The paper also gives the impression that there's still a lot to be learned about how the brain functions. It's hard to find a biomarker if you don't even know all the chemicals or structures in the brain that are supposed to be there.
I'm thinking it might be a good idea to add to MEpedia a page which is a repository of ME/CFS studies which had deconditioned controls. This would be a reference of data which has applied another level of due diligence that it truly applies to ME/CFS, and one could have more confidence that it's true about ME/CFS itself.
Maybe also even studies that did not have such a control, but the same abnormality was tested in another study using a deconditioned group and a healthy group.
Maybe also even studies that did not have such a control, but the same abnormality was tested in another study using a deconditioned group and a healthy group.
Studies controlling for deconditioning or other confounders
Got it started. Not super easy finding studies to add. The one I added so far compares two studies testing muscle acidosis after exercise - one in ME/CFS, one in primary biliary cirrhosis, a condition they say causes a similar level of fatigue. Not sure *how* similar though.
I might include the buspirone challenge test, which differentiates ME/CFS from healthy controls, but has also been tested in numerous other conditions, such as depression, mania, non-ulcer dyspepsia, and social anxiety, some of which also produce similar results to ME/CFS and some which do not differ from healthy controls.
Got it started. Not super easy finding studies to add. The one I added so far compares two studies testing muscle acidosis after exercise - one in ME/CFS, one in primary biliary cirrhosis, a condition they say causes a similar level of fatigue. Not sure *how* similar though.
I might include the buspirone challenge test, which differentiates ME/CFS from healthy controls, but has also been tested in numerous other conditions, such as depression, mania, non-ulcer dyspepsia, and social anxiety, some of which also produce similar results to ME/CFS and some which do not differ from healthy controls.
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Does your new version show up when you go to the page? I see it in history, but the page itself is unchanged. I've tried Purge and using another browser.
Yann04
Senior Member (Voting Rights)
@forestglip I think Rob Würst studies both people in bedrest and pem and has stated on multiple occasions the abnormalities are different. maybe his unite to fight talk and his research might be relevant to the mepedia page you are making.
Oh nice, I'll dig into those, thanks!
Merged posts
And please also compare to very deconditioned or other unhealthy people so we know whether or not the biomarkers are found in all deconditioned or unhealthy people. In that linked thread, we brainstormed some potential deconditioned control groups, such as bedbound hospital patients or people with severe muscular dystrophy.
And please also compare to very deconditioned or other unhealthy people so we know whether or not the biomarkers are found in all deconditioned or unhealthy people. In that linked thread, we brainstormed some potential deconditioned control groups, such as bedbound hospital patients or people with severe muscular dystrophy.
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Muscular dystrophy may not be a good example of pure deconditioning as a negative control, though potentially a positive control. Eg the vascular and coagulation systems have been implicated in DMD.
Advancing Biomarker Discovery and Therapeutic Targets in Duchenne Muscular Dystrophy: A Comprehensive Review (2024, International Journal of Molecular Sciences)
The Role of MicroRNA in the Pathogenesis of Duchenne Muscular Dystrophy (2024, International Journal of Molecular Sciences)
Structural and Functional Alterations of Skeletal Muscle Microvasculature in Dystrophin-Deficient mdx Mice (2015, The American Journal of Pathology)
Targeting angiogenesis in Duchenne muscular dystrophy (2019, Cellular and Molecular Life Sciences)
Serum levels of vascular endothelial growth factor elevated in patients with muscular dystrophy (2008, Brain and Development)
Coagulation system activated in Duchenne muscular dystrophy patients with cardiac dysfunction (2005, Brain and Development)
Coagulation and fibrinolysis disorder in muscular dystrophy (2001, Muscle & Nerve)
The Role of MicroRNA in the Pathogenesis of Duchenne Muscular Dystrophy (2024, International Journal of Molecular Sciences)
Structural and Functional Alterations of Skeletal Muscle Microvasculature in Dystrophin-Deficient mdx Mice (2015, The American Journal of Pathology)
Targeting angiogenesis in Duchenne muscular dystrophy (2019, Cellular and Molecular Life Sciences)
Serum levels of vascular endothelial growth factor elevated in patients with muscular dystrophy (2008, Brain and Development)
Coagulation system activated in Duchenne muscular dystrophy patients with cardiac dysfunction (2005, Brain and Development)
Coagulation and fibrinolysis disorder in muscular dystrophy (2001, Muscle & Nerve)
Hmm, yeah, I hadn't looked at it from the angle that many deconditioning markers might depend on normal muscle function in order to be similar across conditions (although we're not sure muscle function is even normal in ME). Another option could be people paralyzed from the neck down from spinal trauma.
Although even with muscular dystrophy, if you see that a biomarker looks exactly the same in people with MD and healthy controls, and is wildly different in ME, I think that'd be a good clue that it's probably not related to not using muscles, because if it was related to muscles, you would expect it to be different between MD and HC as well.
I'm not sure, this is straining my foggy brain. I'm trying to think of a mechanism where HC and MD could look the same in a biomarker but ME looks different, but where the marker difference is due to not using muscles.
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Kitty
Senior Member (Voting Rights)
I guess you could do a study on pwME and controls over the age of 65? There are plenty of sporty older people, of course, but there are also many who're no more active than folk with mild/moderate ME.
I rent a bungalow on an independent living development entirely populated by them. A combination of painful hips, knees and backs worn out by the physical jobs working-class people do, being retired and not having demanding care responsibilities, and having a low key social life that revolves around seated activities, means they'd be well matched with me.
Yeah, that's a good thought. I'd feel a lot better about such a study if they put activity trackers on everyone for maybe a week to make sure the activity levels are at or below pwME, and didn't just use questionnaires.
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