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Myalgic encephalomyelitis or chronic fatigue syndrome: how could the illness develop?(2019) - G.Morris,Maes,Berk,Puri

Discussion in 'BioMedical ME/CFS Research' started by Sly Saint, Feb 13, 2019.

  1. Sly Saint

    Sly Saint Senior Member (Voting Rights)

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    https://link.springer.com/article/10.1007/s11011-019-0388-6
     
  2. Andy

    Andy Committee Member & Outreach

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    The paper is open access if anyone wants to have a read.

    I don't think they are trying to be funny or ironic with this bit but hard to be sure. ;)
    To those of you, like me, wondering what endotoxin tolerance might be this bit starts to explain. (Edited to add line breaks only)
    ETA: Smiley at the end of my comment showing they had repeated "slow thinking".
     
    Last edited: Feb 13, 2019
  3. S-VV

    S-VV Established Member

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    It's a great paper, if a little convoluted, but very up to date. They place emphasis on pem as a necessary part of study inclusion, which is great.

    The two strong points imho are the correlation of miRNA to immune dysregulation, and the conexion of tgf, il10 and cxcl8 with a hypoinmune state.

    They tie it all with a Lps-tolerance homeostatic state, where the body becomes "tolerant" to inflammatory stimuli, and enters a hypoinmune and hypometabolic state, shifting from oxphos to aerobic glycolisis and finally to b-oxidation as the source of ATP. However they write that in this state carnitine palmitoyltrasnferase I is upregulated, which I don't think matches the latest metabolome study.

    Finally they state that this hypo state is sustained by a high IDO activity and high kynurenine production. Kinda the opposite of the metabolic trap.
     
  4. Andy

    Andy Committee Member & Outreach

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  5. Andy

    Andy Committee Member & Outreach

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    Interesting to look at the author's affiliations, shows not all in the psych world are beholden to the BPS crowd.
     
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  6. Ravn

    Ravn Senior Member (Voting Rights)

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    Thanks for the summary @S-VV. Very helpful because this article is waaay over my head but it does sound interesting - or is it just the technical lingo fooling me?

    I did note - and appreciate - the number of times the authors commented on the impact of patient selection criteria on study results. But they did seem to equate Fukuda with international consensus criteria (in lower case, as opposed to International Consensus Criteria as in ICC)?

    Anyway, is there anyone here with the necessary knowledge and energy to provide a more detailed summary, in plain English?

    ETA: Also, it's not clear from the paper if the authors understand the difference between common-garden exercise intolerance and PEM. They seem to think their model of ME can explain exercise intolerance, which is good, but as far as I can see they don't explain PEM - though that's very possibly due to me not understanding much of the paper.
     
    Last edited: Feb 14, 2019
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  7. Snow Leopard

    Snow Leopard Senior Member (Voting Rights)

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    It's an interesting hypothesis, but unfortunately, it's also almost certainly wrong.
     
  8. Inara

    Inara Senior Member (Voting Rights)

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    Why? Why wouldn't it be correct for a subset? Or for a subset of symptoms? Could the direction be interesting? Why not?

    I agree though that nitrosative stress maybe is not the answer alone. (Is there any evidence of nitrosative stress/hypernitrosylation in ME or elsewhere?)

    They are not speaking of endoplasmic reticulum (ER) stress explicitly, but about elevated NO and ROS (amongst others), which leads to ER stress. ER stress is found in several diseases. There are indications in Alzheimer's, Parkinson's, ALS, inflammation etc. (though, up til now, these are only animal experiments, so...). Exercise, heat, fasting, infections etc are triggers of ER stress. They also mention LPS (Lipopolysaccharide), which is an ER stress trigger, too, and may interrupt with signaling pathways. Yet, there are so many ways that can lead to ER stress. And I think it's complex.

    I don't think it's the one and only cause, but maybe it plays a role? Personally, I think there might be something like a disruption in a signaling pathway (which may be different in different persons with ME, leading to a similar problem - for instance, it seems hypernitrosylation may impact similar pathways as, e.g., the IP3 pathway), which may contribute to ER stress, amongst others, which may lead to activity, heat, cold etc. intolerance, while cleavage of the misfolded proteins takes longer as usual or is otherwise disrupted, which may lead, amongst others, to a decrease of calcium transport to the mitochondrion, which leads to decreased ATP production etc. etc. (together, could this be PEM? and why not?).

    They mention calcium delivery to mitochondria (which is crucial for them to function properly), although I don't see why L-type calcium channels play the major role here. These are positioned on the plasma membrane. Does the mitochondrion move there for calcium transport? However, the ER and mitochondrion are in close proximity to each other, in the nanometer range (or the mitochondrion can move there), and it's the calcium from the ER that's "puffed" into the mitochondrion.

    Oh, I see a part of the authors already published in 2017 about the topic:
    https://link.springer.com/article/10.1007/s12035-016-9975-2
    There they also explain "hypernitrosylation".

    Edit: I need to correct: mitochondria can also move to the plasma membrane.
     
    Last edited: Feb 19, 2019
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  9. Inara

    Inara Senior Member (Voting Rights)

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    I found this interesting:

    Is this correct, does anyone know?
     
  10. Estherbot

    Estherbot Senior Member (Voting Rights)

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    Interesting list of authors...

    Anybody know more about Gerwyn Morris or Michael Maes?

    On some of the quoted papers Morris is listed as a resident of Llanelli....(@JohnTheJack a near neighbour to you)
     
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  11. Estherbot

    Estherbot Senior Member (Voting Rights)

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    Like most of you I have struggled with terminology & language used.

    However I did find this via Self Hacked (admittedly not always the most reliable source, however you may find the explanations on leaky gut, endotoxins, LPS etc a useful starting point.)

    https://selfhacked.com/blog/lipopolysaccharides
     
  12. JohnTheJack

    JohnTheJack Moderator Staff Member

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    Interesting. I didn't know of him, but he has a page on MEpedia.
    https://me-pedia.org/wiki/Gerwyn_Morris
     
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  13. duncan

    duncan Senior Member (Voting Rights)

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    Gerwyn was a force of nature in the XMRV days.
     
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  14. lansbergen

    lansbergen Senior Member (Voting Rights)

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    Maes always was interested in the biology

    Gerwyn is a patient. Maybe there are still some posts of him om phoenixrising.
     
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  15. lansbergen

    lansbergen Senior Member (Voting Rights)

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    Yep
     
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  16. jpcv

    jpcv Established Member (Voting Rights)

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    Would you care to elaborate a little bit?
     
  17. Michiel Tack

    Michiel Tack Senior Member (Voting Rights)

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    Michael Maes is a psychiatrist from Belgium. I think he was one of the pioneers of the inflammation theory in depression. In the years 2000, he started studying CFS with pretty much the same idea in mind: that researchers focus too much on behavioral aspects and too little on biological elements such as inflammation. His theory is that ME/CFS could be another example of a runaway inflammatory process. One mechanism that is central to his theory is "leaky gut", the idea that (elements of) gut bacteria "leak out" to other parts of the body and cause immune activation.

    Maes has been very critical of GET/CBT and the biopsychosocial model at a time when this was not common in academia. He has published about this together with Frank Twisk. See:
     
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  18. Stuart

    Stuart Established Member

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    Much of the history of that period was lost in the great purge of entire threads, massive after the fact editing and revision on forums leading to an exodus and the formation of new forums (themselves with great content now lost as they went into the bit void). Like the termination of the CFSAC and removing its online record into the memory hole, it can be pretended things either never happened, or happened other than they did.
     
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  19. Dolphin

    Dolphin Senior Member (Voting Rights)

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    I'm afraid some of my memories from that time are not very fond.
    I remember one time on the forum that no longer exists, somebody doxxed me giving my name (and not just my first name) alongside my username. This was at a time when I was a regular poster on the forum.
    I reported the message. Rather than edit the message, the moderator contacted person and asked them about it. They didn't want to change it. So the moderator said to me they were going to leave it.
    It was changed a day later, after the user (not moderator) changed their mind, but still my name and username has been out there at all that time.

    I didn't feel able to highlight this in the meantime elsewhere as it would draw attention to my name.

    The same moderator once told me that moderating wasn't much work on that forum. I wasn't surprised, given they weren't willing to properly act on a message like that.

    (I know one isn't supposed to discuss order fora but it no longer exists now so hopefully not a problem)
     
  20. MyalgicE

    MyalgicE Established Member (Voting Rights)

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    rvallee, Amw66, Ravn and 1 other person like this.

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