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A 50,000 Foot Overview of Major ME/CFS Theories

Murph

:)
Messages
1,799
Hi Jesse...

You also have Melbourne Bioanalytics who found that CCC diagnosed patients were 21 times more likely to have gene mutations in G protein coupled Receptors than controls and 12 times more likely to have mutations in R Helicases...
https://www.melbournebioanalytics.o...mecfs-by-neil-mcgregor-written-transcription/
Yes. I wanted to make sure Armstrong and McGregor weren't overlooked. And their associated clinician, Dr Lewis.

They are probably too scientific to just have one pet theory but you could say maybe gut dysbiosis combined with genetic susceptibility leading to metabolic disruption of a sepsis type?

(it's also worth mentioning their fecal microbiome collaborator who end up in some of their studies, Dr Butt. The poop specialist! Not a joke, that's his real name.)
 

Jesse2233

Senior Member
Messages
1,942
Location
Southern California
A good overview of the absurdity of trusting in a doctor's theory and treatment plan.
Makes me sad how spot-on this is - we really are nowhere for the moment.

I agree that these can all see pretty disparate, but there's a chance many of them could be simultaneously correct (for all / most / or a subgroup).

Are you ready for this...

Genetic predisposition (Kerr / Armstrong / McGregor) leads to suboptimal liver function (@mariovitali) as well as a propensity toward gut dysbiosis and inflammation (KdM) which can be triggered by a variety of pathogens / environmental insults (Chia / Hyde / Ramsay / Jardin / Nicholson / Lerner / Montoya / Cutler / Weir / Miktovas / Shoemaker / Brewer) creating a mystery molecule (Fluge + Mella / R. Davis) that sustains chronic immune dysfunction (Scheibenbogen / M. Davis / Behan / @necessary8 / @Jonathan Edwards) which in turn impairs cellular activity in a variety of ways (Myhill / Pall / F. Davis / Van Kronenburg) causing brain dysfunction (Goldstein) all within the context of a stuck molecular response to trauma (Naviaux).
 

Gemini

Senior Member
Messages
1,176
Location
East Coast USA
I’ve tried to keep each theory to one simple sentence. Let me know if I’ve left out or grossly misstated anything important.

Jay Levy--chronic immune system activation (1980-90's)
Nancy Klimas--natural killer cell (NK) dysfunction
Anthony Komaroff--low-grade encephalitis
G. Lange--acquired brain injury (ABI), functional not structural

Nice list @Jesse2233! Like the simple sentence format!:thumbsup:
 
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Learner1

Senior Member
Messages
6,305
Location
Pacific Northwest
I agree that these can all see pretty disparate, but there's a chance many of them could be simultaneously correct (for all / most / or a subgroup).

Are you ready for this...

Genetic predisposition (Kerr / Armstrong / McGregor) leads to suboptimal liver function (@mariovitali) as well as a propensity toward gut dysbiosis and inflammation (KdM) which can be triggered by a variety of pathogens / environmental insults (Chia / Hyde / Ramsay / Jardin / Nicholson / Lerner / Montoya / Cutler / Weir / Miktovas / Shoemaker / Brewer) creating a mystery molecule (Fluge + Mella / R. Davis) that sustains chronic immune dysfunction (Scheibenbogen / M. Davis / Behan / @necessary8 / @Jonathan Edwards) which in turn impairs cellular activity in a variety of ways (Myhill / Pall / F. Davis / Van Kronenburg) causing brain dysfunction (Goldstein) all within the context of a stuck molecular response to trauma (Naviaux).
Of course!;)
 
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Gemini

Senior Member
Messages
1,176
Location
East Coast USA
Are you ready for this...

Genetic predisposition (Kerr / Armstrong / McGregor) leads to suboptimal liver function (@mariovitali) as well as a propensity toward gut dysbiosis and inflammation (KdM) which can be triggered by a variety of pathogens / environmental insults (Chia / Hyde / Ramsay / Jardin / Nicholson / Lerner / Montoya / Cutler / Weir / Miktovas / Shoemaker / Brewer) creating a mystery molecule (Fluge + Mella / R. Davis) that sustains chronic immune dysfunction (Scheibenbogen / M. Davis / Behan / @necessary8 / @Jonathan Edwards) which in turn impairs cellular activity in a variety of ways (Myhill / Pall / F. Davis / Van Kronenburg) causing brain dysfunction (Goldstein) all within the context of a stuck molecular response to trauma (Naviaux).
The ultimate "holistic systems biology model"!!!:balloons:

Thanks @Jesse2233!
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
I wonder how many subsets of these are (or can be made) consistent with each other.
This is a burning question that has bugged me for years. Lots of researchers come up with subgroups, but are these subgroups stable for all of the research? Do different responses in post exercise hormones match the subgroups from other causes? It would seem it should be answerable, but nobody has done it.
 

Murph

:)
Messages
1,799
I agree that these can all see pretty disparate, but there's a chance many of them could be simultaneously correct (for all / most / or a subgroup).

Are you ready for this...

Genetic predisposition (Kerr / Armstrong / McGregor) leads to suboptimal liver function (@mariovitali) as well as a propensity toward gut dysbiosis and inflammation (KdM) which can be triggered by a variety of pathogens / environmental insults (Chia / Hyde / Ramsay / Jardin / Nicholson / Lerner / Montoya / Cutler / Weir / Miktovas / Shoemaker / Brewer) creating a mystery molecule (Fluge + Mella / R. Davis) that sustains chronic immune dysfunction (Scheibenbogen / M. Davis / Behan / @necessary8 / @Jonathan Edwards) which in turn impairs cellular activity in a variety of ways (Myhill / Pall / F. Davis / Van Kronenburg) causing brain dysfunction (Goldstein) all within the context of a stuck molecular response to trauma (Naviaux).


That is all perfectly logical! But I think we want some research to be dead ends. We need more theories to be falsified so we can chuck them out and zero in on those that remain...
 

dreampop

Senior Member
Messages
296
This is pretty misleading for some of these researchers, research focus or treatment focus ≠ theory. As someone said in the symposium, they all are touching a part of elephant and so they necessarily talk about that side of it, while knowing it's only a piece in the puzzle.
 

Jesse2233

Senior Member
Messages
1,942
Location
Southern California
This is pretty misleading for some of these researchers, research focus or treatment focus ≠ theory. As someone said in the symposium, they all are touching a part of elephant and so they necessarily talk about that side of it, while knowing it's only a piece in the puzzle.

That's a fair point. Just because a researcher / doctor is focused on one area doesn't mean they are necessarily blind to others
 

Gemini

Senior Member
Messages
1,176
Location
East Coast USA
EM Tan-- Identification and characterization of autoantibodies (1996)
Mark Demitrack-- Impaired activation of the hypothalamic-pituitary-adrenal(HPA) axis (1991)
Elaine DeFreitas--Association between an HTLV-II-like retrovirus and ME/CFS (1991)
LO Simpson-- Altered red blood cell shape, inadequate oxygen delivery, and impaired capillary blood flow(1993)
 

Mel9

Senior Member
Messages
995
Location
NSW Australia
Hey guys - thought it might be interesting to list out all the major ME/CFS causal theories in one place.

This can act as a primer for newbies, and as a way to look at everything in a comprehensive manner in the hopes of making fresh connections.

I’ve tried to keep each theory to one simple sentence. Let me know if I’ve left out or grossly misstated anything important.

——————————

Enlightened GPs / laypublic - post-infectious non-specific immune dysfunction

Unenlightened GPs / laypublic - psychological construct / wastebasket diagnosis

Melvin Ramsay - polio-like illness following an enterovirus infection

John Chia - chronic non-cytolytic enterovirus infection

Byron Hyde - diffuse lower brain injury following enterovirus infection

Martin Lerner - chronic abortive herpes family infection

Kenny De Meirleir - inflammatory gut dysbiosis following tick-born illness

Jay Goldstein - post-infectious central sensitization of the brain

Jose Montoya - chronic HHV infection of the CNS

Carmen Scheibenbogen - autoimmunity against muscarinic and adrenergic receptors

Robert Naviaux - cell danger response mediated by purinergic signaling

Ron Davis / Fluge + Mella - a large molecule in serum disrupting cellular metabolism

Mark Davis - nonspecific antigen causing inflammatory T-cell dysfunction

Sarah Myhill - multicausal dysfunction of various mitochondrial mechanisms

Neil McGregor / Chris Armstrong - genetic susceptibility to gut dysbiosis causing sepsis-like metabolic state

Ritchie Shoemaker / Joseph Brewer - mold causing immune dysfunction

Jarred Younger - chronic microglial inflammation

Rich Van K / Fred Davis - blockage in glutathione production

Michael Van Elzakker - chronic infection of the vagus nerve

Martin Pall - dysfunction of the nitric oxide cycle

Garth Nicholson - chronic mycoplasma pneumonia infection

Peter Behan - enterovirus driven autoimmunity against ATP translocator

Andy Cutler - chronic heavy metal toxicity

Judy Miktovas - chronic XMRV / HERV infection

William Weir - chronic non-specific retrovirus infection

Cecil Jardin - chronic non-specific bacterial infection

Gupta / Hooper / Neuffer - non-specific autonomic dysfunction

Chalder / White / Wesely / Parker - self-limiting fear based beliefs

The 1980s - Candida

The 1990s - EBV

——————————

Some PR theories

@necessary8 - autoantibody to CD38 causing metabolic dysfunction through eATP

@Jonathan Edwards - 6+ subtypes involving immune sensitization, autoimmunity, and chronic inflammation

@mariovitali - suboptimal liver function leading to immunological / metabolic dysfunction


Goodness! No wonder I'm confused
 

Gemini

Senior Member
Messages
1,176
Location
East Coast USA
Sidney Grossberg-- JHK virus infection (1993)
Hugh Fudenberg-- persistent antigenic stimulation by dead, incomplete, or latent viruses (1993)
Paul Cheney--chronic, immunologically-mediated inflammatory process of the CNS (1992)

@Jesse2233 Paul Cheney has a system's perspective perhaps influenced by his physics background.
 
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