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Wolfe Hypothesis ~ Key causative processes involved in CFS/CFIDS/M.E.

Discussion in 'General ME/CFS Discussion' started by John H Wolfe, Sep 13, 2012.

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Does this theory seem plausible?

  1. Yes

    9 vote(s)
    24.3%
  2. Didn't read it

    5 vote(s)
    13.5%
  3. Not sure I fully understand it

    5 vote(s)
    13.5%
  4. No

    18 vote(s)
    48.6%
  1. John H Wolfe

    John H Wolfe Senior Member

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    Haha, no comment

    Ditto

    Beyond bizarre, it's scandalous! However, just to reiterate, as far as I'm concerned, such malpractice is not the same as proof that CBT approaches do not bring benefits
     
  2. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    There is also probably no proof that there is no flying teapot in space, or that mice are not secretly plotting to take over the world.

    There is also no proof that there is a flying teapot in space, or that mice are secretly plotting to take over the world.

    And I am not aware of any proof that CBT can help to treat ME/CFS. Do you have any?
     
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  3. John H Wolfe

    John H Wolfe Senior Member

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    Have you not seen soviet space craft? :lol:

    Was alien lizards last time I heard, clearly out of the loop..

    Nope, just anecdotal/experience of it having a positive impact, plus those studies (we can trust) that suggest that in subjective terms at least, some patients do see benefits

    Btw, Elph was good enough to send me a couple of articles, the first of which I've just got round to having a proper look at and the discussion appears to accord, in principal, with my thinking on potential explanations for the interplay with central effects and (important, if plausibly epiphenomenal) GI disorders to a T!:

    "... a variety of findings [from various studies] ... suggesting a state of low grade inflammation or immune activation ... [associated] increased serum concentration of cytokines have been interpreted as evidence of a spill-over from a primary focus in the gut"
     
  4. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    This paper was first discussed on Phoenix Rising here in 2010.
     
  5. Valentijn

    Valentijn Activity Level: 3

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    Exactly. I think in one or two of the three studies they didn't mention actometers at all. In the Stulemeijer paper they do mention that they were used, and in a context which makes it sounds like the results support the other outcome measurements. But without ever reporting the results.

    And yet, these studies were better than most, as they're among the very very few CBT studies which even use actometers.
     
  6. John H Wolfe

    John H Wolfe Senior Member

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    Thanks. I wonder whether any of the contributors have found the drugs they mention to be helpful. Personally I prefer to try organic antibacterials (first) but I guess if your problem is viral, or a viral-bacterial mix, then you may need to go nuclear!
     
  7. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    Have you tried a search? I found the thread by searching for keyword 'lakhan' from March 2010 onwards.

    You might be surprised what you can find on this site by searching. You may get answers to a lot of your questions, and be able to really gen up on papers in your areas of interest and read useful discussions about them.

    Saves reinventing the wheel, as it were!
     
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  8. Snowdrop

    Snowdrop Senior Member

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    With regard to the efficacy of CBT lets not overlook the power of the 'white coat syndrome'. Experts applying their theories on test subjects may no longer be white males with horn rimmed glasses and decked out in white lab coats but their position vis a vis the subject is one of authority. Two things come to mind with regard to subjective responding. Ill people want (desperately) to get well. When they come in for treatment there is an expectation and hope that colours any immediate response. Also, we are geared to please. This is because we are social creatures but also when you add an 'expert' there is often deferral. (MEer's have that social nicety knocked out of them eventually). If as seems to be the case you are talking about teenagers, well, they may not take the garbage out when a parent asks but they're likely to respond positively to the expert because the power gap is even larger and someone who is not their parent seems to be taking a keen interest in them and their condition.
     
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  9. John H Wolfe

    John H Wolfe Senior Member

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    Finished going through that article and developing the concepts in the context of my disease model yesterday, have to say it's one of the most helpful/interesting/thought provoking papers I've come across! :)

    The H2S connection with nerve impulse amplification and implied gut-CNS interface, and hence mood, modulation was of particular interest and has helped me broaden, and deepen, the picture re: my pathways involving infection

    I might be, aye, and I do like to examine things through an experiential lens/see what others have to say (hence posting here in the first place prior to completion); little short on time/energy at the minute tho

    Reinventing the wheel is fun though, if you're a problem solving addict like me! Granted insights do come quicker/dead end leads are invalidated sooner if you take a multi domain approach, and I do try, it's just I'm male, so multitasking is a little tricky..
     
  10. John H Wolfe

    John H Wolfe Senior Member

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    All fair points aye, subjective measures can only tell us so much

    I guess it's a little hard to control for these effects as that would ostensibly mean giving the control a non-CBT placebo pseudo-psychological treatment (to control for placebo, psycho-therapeutic effects of the attention they receive, and associated desire to please), as well as telling the CBT cohort that the treatment they are receiving is purely experimental and not necessarily expected to work on anyone, without undermining the efficacy of delivery (CBT/NLP are obviously best administered in an upbeat/optimistic fashion)
     
  11. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    Re 'implied' gut-CNS interface, are you aware of the vagus nerve? If you do a search here using the word 'vagus' and/or 'vagal' you will get a large number of hits.

    Why do you consider mood to be significant?
     
  12. John H Wolfe

    John H Wolfe Senior Member

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    Yup, I don't currently comment too much on specific nerves in my discussion but VanElzakker (2013) theory re: neurotropic viruses vs. exaggerated sickness behaviour gets a mention, along with tropism of enteroviruses for the CNS.(Chia, 2005)

    Some relevant excerpts:

    'factors associated with migraine pathophysiology may contribute to the type of headaches and cognitive impairments associated with ME/CFS.' ~ towards the end of the cortical spreading depression (CSD) model of migraine: "...pain, emotion, memory, frontal processing and other inputs converge on the anterior cingulate gyrus and interfere with its executive decision-making functions".(Rayhan et al. 2013)

    'It has been argued that stress system dysregulation may have the primary role in normal physical, mental and emotional adaptability.(Van Houdenhove et al. 2013)

    Psychological stress results in immune activation and cytokine elevation, a (further) source of sickness behaviour,(Anisman & Merali, 2003) the severity of the symptomatic manifestation of which is a strong function of basal levels of stimulated cytokines IL-6 and TNF-α in ME/CFS, already noted as being associated with HPA control and found to be elevated in ME/CFS.(Gaab et al. 2005).

    HPA responses to sickness behaviour signals result in (further) mood dysregulation and enhanced potential for the evolution of depressive/anxiety disorders in the context of a history of stressful experiences.(Anisman & Merali, 2003) Additionally, as discussed, through their impact on pain facilitation mechanisms, forebrain products such as cognitions, emotions, attention, and motivation, influence the clinical pain experience,(Zusman, 2002) hence the potential for ‘cognitive emotional sensitisation’.(Brosschot, 2002)

    Combined with the rest of the model, this picture implies a circular relation between the psychophysiological affectation of mood and stress system dysregulation by factors directly/indirectly associated with central sensitivity, and enhanced potential for the affectation of (further) central sensitisation by (enhanced) psychopathological modulation of nociceptive regulation.'

    © John H Wolfe (2013)​
     
  13. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    The vagus nerve is a real biggie, and considered important in many processes.

    Some of that may be credible, but just a few possible reasons for caution:

    I hardly get headaches at all (just mild ones that appear to be sinus-related), and have no history of migraine, my only possible vaguely migraine-related experiences in the 19 years of having ME being two brief episodes of what appeared to be scintillating scotoma, which lasted 15 and 30 mins and involved no pain or other symptoms.

    Chronic stress impairs rather than activates the immune system. I do believe that early-life stress could contribute to ME and/or other autoimmune conditions by this means. There are some very good threads on the immune aspects, especially this one.

    As I've said before, I do not have an abnormally-high level of pain. Indeed, a nurse was bewildered by my lack of pain when I broke my wrist. My muscles ache when they are as tight as a piano wire, as one would expect. I get mostly-mild pain associated with sinus congestion - again normal. I get mild gut pain, probably due to the gut having to deal with an excessive volume of lactate/lactic acid - again, to be expected.

    My lifelong anxiety has been dramatically reduced by reducing carbohydrates, cutting out gluten and taking certain supplements.

    So would you expect such improvement to be followed by a remission of physical symptoms?

    BTW I am not aware of any good evidence that people with ME have a higher rate of depression than the general population. Anxiety, yes, but from my experience and that of others, this may turn out to have a physical (gut-related) cause. There are threads on this too.
     
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  14. John H Wolfe

    John H Wolfe Senior Member

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    Aye, same really, although my mother has a history of migraine and I have had one or two over the years. Usually just get low-grade heavy head headaches (particularly in the AM)

    Ta for that :) I have touched on some of the reasons why Rituximab may be producing results in my discussion:

    'Rituximab is a monoclonal antibody, notably purportedly effective in the treatment of peripheral neurological diseases, that depletes B cells, inhibits the production of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and blocks Tumour necrosis factor alpha (TNF-α).

    NF-κB is a protein complex that stimulates the production of adhesion molecules and produces inflammatory cytokines including interleukin-1β (IL-1β) – an inflammatory cytokine, which sensitises peripheral nerves, increases the rate of glycolysis and compromises mitochondrial functions.(Morris & Maes, 2012a)

    TNF-α is an inflammatory cytokine that mediates altered central nervous system (CNS) excitability, (Riazi et al. 2008) induces and up-regulates IL-1β,(Woolf et al. 1997), is known to impair astroglial glutamate uptake,(Fine et al. 1996) and has been found to be significantly elevated in ME/CFS patients.(Moss et al. 1999)

    Glutamate is the most abundant neuroexcitatory neurotransmitter in the CNS.

    Another TNF-α inhibitor, etanercept, has apparently demonstrated considerable benefits.(Lamprecht, 2001)'

    Rowe believes our increased resting muscle tone relates to irritable nerves, often subject to mechanical tension

    Do you do anything to help mitigate that? I've found manual lymphatic drainage quite helpful. Probably tempting fate by saying this but I haven't had a sinus problem/sinusy cold for as long as I've been doing Perrin Technique (18 months) :)

    Excellent. I am the same, although my dietary discipline has lapsed a little out of convenience

    Improvement in what, GI bacterial dysbiosis?

    I'm not sure I compare prevalence rates in that sense in my discussion, although I do mention:

    'Thus, the glial activity described results in neuroexcitation, neuroinflammation and neurodegeneration, and hence (further) microglial multiplication – subject to neuronal damage, and is associated with depressive-like behaviour and cognitive deficits.(Norden & Godbout, 2012). Cognitive deficits are a hallmark of ME/CFS,(Shanks et al. 2013) and around half of patients demonstrate evidence of mild to moderate depression.(Light et al. 2013)'

    Aye, as I may have mentioned, from what I have read there appear to be a plethora of psychophysiological factors (including, but not limited to, GI impacts, in my view)
     
  15. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    I'm not familiar with the term 'irritable nerves'.


    Nothing worked until I cut out gluten, reduced carbs, etc. That did it. I still get a bit of congestion which I think is due to dust mites, but if I hoover the house I will get the adverse effects of exertion. Think I will have to pay someone to vacuum about once a week!

    I was referring to my preceding text:


    So I am asking: if you think that anxiety is an important factor in (causing? perpetuating?) ME/CFS, would you expect a reduction in anxiety to be followed by remission of physical symptoms?

    [depression]

    Again, I was referring to preceding text, in this case your quotes of a study referring to
    Did the Lights compare CFS patients to others with chronic disabling illnesses, or with controls? Chronic disability can itself cause mild depression, perhaps partly due to poverty and inability to exercise or get out. But from my reading of messages from people with ME/CFS there is little evidence of a high prevalence of
    I have experienced depression due to traumatic life events, and know what it is like. It is typified by a lack of motivation. People with ME/CFS appear to be generally extremely highly-motivated, indeed remarkably so in light of their problems.
     
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  16. Snow Leopard

    Snow Leopard Senior Member

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    Yes, the patients with post-cancer fatigue had a rate of 43% of 'mild to moderate' on the "Quick Inventory of Depressive Symptomatology-Self Report 16". This is not the same as clinical depression and I personally wouldn't read too much into this alone.

    @John H Wolfe

    Pulling all the observations made so far makes for an interesting story, but it is not a hypothesis (or a set of hypotheses) unless it makes specific testable observations. It needs to be something that you could present to researchers and have them easily design an experiment to test it.

    If you have access to scientific literature, you can actually do this using existing studies, which you are not yet familiar with. Eg when trying to understand the observations of different HPA axis functionality compared to healthy controls, I made a series of hypotheses and then went and looked to see whether those hypotheses had been tested. Some of them had been tested, which allowed me to build a few competing theories. I had also made specific predictions about GR expression for example, therefore my theory took on a new direction after the most recent study from Light et al.
     
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  17. John H Wolfe

    John H Wolfe Senior Member

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    Essentially a shorthand colloquialism for what I've been talking about in relation to what Rowe describes as: "irritable peripheral tissues" subject to: "movement restrictions" and "neural provocation" associated with "biomechanical and behavioural factors", and hence "neuromuscular strain"

    I did the same during the autumn last year so I suppose that could also have been a factor with me

    Does PEM include a sinus issue for you then?

    I'm no clinician but, on a theoretical level, partial remission perhaps, yes, but there are many potential sources of temporal summation, or ‘wind-up’, including cognitive/emotional yes, but not limited to those, nor limited to anxiety within that group

    Furthermore, because such forebrain products appear both psychophysiological and, to an extent, psychosocial, products of the illness, as well as psychopathological contributors to it (via descending pain facilitation, and other adverse mechanisms related to 'stress' and central sensitisation), it is difficult to disambiguate contributory cause and effect. If anxiety or depression are reduced that may only mean that one part of the symptomatological picture is improved, whilst core processes remain active, albeit probably at a lower level

    I'm not sure about prevalence rates for anxiety but I understand that:

    "..the Val(158)Met [COMT gene] polymorphism is associated with obsessive-compulsive disorder in men and with anxiety phenotypes in women.(Harrison & Tunbridge, 2008)"

    I do not suffer with anxiety and nor do many of the (admittedly relatively few) men I have met who have ME/CFS but I do have compulsive traits, and I have met quite a few female members of the community who do suffer with anxiety. In one study 88% of those ME/CFS patients who had 'depressive symptoms' were female, but only 35% of those who did not were female

    This narrow/anecdotal picture is, to me, suggestive that anxiety and depression are relatively highly correlated with illness in female patients owing to things like sexually dimorphic effects (associated with distinct hormone interactions) and distinct brain structure (enhanced limbic systems etc) and that an improvement in those features of the disease could be expected to be associated with a more general remission I suppose - rather loose to say the least but there you go!

    Oh right, it says: "enhanced potential for" e.g. puts patients at a higher risk of developing such co-morbid disorders

    Indeed, and my sense is that psychological issues are in many cases a 'psychophysiological and, to an extent, psychosocial, product of the illness'
     
  18. John H Wolfe

    John H Wolfe Senior Member

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    Yeah. I need to put a lot of thought into how I'm going to present this/attempt to get it published when it's finished. At the mo it's a 'hypothesis and conceptual model' but the central hypothesis is pretty vague (synergistic neuro-glial dysfunction) and God knows how I could turn it into a testable hypothesis even if I had the expertise and data to narrow it further

    So essentially it's a review and theoretical disease model for the time being but that doesn't mean it won't sprout testable hypotheses (I already have a few jotted down, although I haven't got round to giving this serious thought)

    That's the ideal end game aye

    Cool. Sounds like you're coming at it from quite a rigorous, scientific angle

    Mine is a layman's approach to reviewing research, something akin to a primitive systems biology approach, aiming to provide a multidisciplinary platform for the greater understanding of the illness by all, including/especially those who, like yourself, prefer to investigate individual elements in a more rigorous/focused sense but could often use some extra ideas as to where to look and why
     
  19. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    Hard to say, but not sure why you ask. The two potential causes of my sinus problems that I know of are diet and dust mites. PEM is obviously an undesirable thing to have in itself - more so than sinus problems as it means that a pathological loop is probably continuing, and one is no further towards remission/improvement.

    [psychopathic] Is that a typo?!
     
  20. Valentijn

    Valentijn Activity Level: 3

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    Yeah, when someone tries to squish different papers from a traditionally dodgy area of research (psychology) into one integrated theory, they're going to get some weird results.
    How shocking - you managed to find a way to suggest that most of us are likely to have certain unflattering psychological disorders, while safely extracting yourself from the group.

    For the third time, you seem to have spectacularly failed to read the research sufficiently to answer some basic questions: how are they diagnosing or defining depression? Is "depressive symptoms" as mentioned in the study the same thing as crossing a threshold for a depression diagnosis? Were physical ME/CFS symptoms considered indicative of depression?

    I know you don't have answers to any of the questions, because the paper doesn't answer them. Though the researchers are not psychobabblers themselves, most of their sources are psychobabblers, and heavily skewed toward psychogenic theories. The odds are extremely good that anxiety and depression assessment was based on having certain symptoms which have physical causation for ME/CFS patients.

    Of course, no appropriate control group involving patients with a better-understood chronic and multi-system was used, and the results for mood disorders among the healthy patients was not shown either. Because the the controls were certainly assessed for the purpose of making comparisons between genetics and mood disorders, it is rather suspect that those results have been withheld, indicating that they were likely quite overzealous in labeling participants as having "depressive symptoms".
    I think you need to stop trying to warp the world to fit your anecdotal picture. You're starting with a conclusion, and working backward, which means the only question is how you're going to present the data to best support your conclusions. Good research should involve looking for answers, rather than looking for justification for your pre-emptive conclusions.

    Your anecdotal picture also seems highly incorrect and insulting, which is not helping.
     

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