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Blocking glucocorticoid receptor in GWI (Klimas at #MECFSConf18)

Discussion in 'Health News and Research unrelated to ME/CFS' started by adambeyoncelowe, May 5, 2018.

  1. adambeyoncelowe

    adambeyoncelowe Senior Member (Voting Rights)

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  2. Amw66

    Amw66 Senior Member (Voting Rights)

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    I have not seen a paper published, but Dr Amalok Bansal had suggested in LiME conference in Sweden 2014, that glucocorticoid B receptor was affected in ME.
     
  3. Sly Saint

    Sly Saint Senior Member (Voting Rights)

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    "
    Veterans told: there is no Gulf syndrome
    By Michael Evans, Defence Editor


    March 25 2006, 12:00am, The Times

    GULF WAR veterans suffering from illnesses since the 1991 conflict were told yesterday that, after 15 years’ research, no single cause had been found for their health problems.

    The final judgment on “Gulf War syndrome”, dismissing it as a recognisable disease, was delivered by scientists from the Royal Society, the leading science academy in Britain.

    In a study of all the work carried out into the syndrome since the conflict, the Royal Society said that it was time to call a halt. “I believe there is little value in conducting further research into the causes,” Simon Wessely, the co-director of King’s College Centre for Military Health Research, said.

    Professor Wessely co-edited a special journal documenting the research findings that was published by the Royal Society…"


    anyone told the Times/Simon Wessely? and the people who gave him a knighthood for his 'work' on this subject?
     
  4. Helen

    Helen Senior Member (Voting Rights)

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    As professor Wessely is a psychiatrist he surely won´t find the cause of the Gulf Syndrome. I wished the Royal Society would listen to Dr. Garth Nicholson a.o. instead, but it is surely cheaper for the well-fare systeme not to. It would be interesting to read the list of references to his claim.
     
  5. Helen

    Helen Senior Member (Voting Rights)

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    Interesting. Here is the video from his talk at the Swedish RME conference in Stockholm, 2014

     
    Last edited: Jun 2, 2018
  6. Hutan

    Hutan Moderator Staff Member

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    Hmm. I am a bit dubious of these mouse models. How do you make a mouse model when you don't know what caused a physiological problem or what that physiological problem is? (Remember that CFS model produced by having the mice/rats? swim until exhaustion?)

    And while the mathematical modelling of biological systems and stable disease states is very interesting and may one day be useful for ME/CFS, I suspect we don't know nearly enough about how the body works yet. Or for that matter, how to define the perturbed start point in ME/CFS.

    There seems to be a big emphasis on high cortisol in GWI, or low cortisol in ME, or, well you know, something wrong with cortisol and, stress... and HPA axis, and PTSD, and, did I say, stress. I'm probably being too harsh with respect to Klimas' work, but that publication in the first post doesn't sound terribly different to the BPS crowd (e.g. that recent hair cortisol paper) apart from the fact that the BPS crowd are certain that the right kind of talking therapy will fix things whereas Klimas and Broderick et al think that medicines are needed.

    Given the lack of evidence for levels of cortisol being abnormal in ME (maybe for some individuals, but not overall), I'm not getting excited about a report of work on blocking the glucocorticoid receptor in ME/CFS, or of success in fixing a GWI mouse model with, presumably, high cortisol and low testosterone.

    Hopefully I'm wrong and they come up with something great.
     
    Last edited: Jun 4, 2018
  7. adambeyoncelowe

    adambeyoncelowe Senior Member (Voting Rights)

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    To be clear: she claims the glucocorticocoid problem is in GWI, not necessarily ME. She doesn't yet have a mouse model for our illness, which appears distinct from GWI. I didn't read it as 'stress causes GWI', but even if she is saying that, it doesn't mean ME follows suit. GWI occurs in the context of major conflict (war, not interpersonal conflict) while ME doesn't.

    Also, the BPS model specifically focuses on psychological and behavioural interventions. Klimas' model involves a biomedical switch to turn something off. Psychological illnesses don't usually get resolved that easily. That an illness involves dysfunctional neurotransmitters does not in itself mean that illness is psychological. Take Parkinson's, where there's a depletion of dopamine (not the only problem, I know, but treatment often involves replenishing neurotransmitters).

    I can see that superficially the two things may look similar, but it's what the researchers conclude from their results. The BPS crowd always twists any finding to support a psychosocial aetiology. I think Klimas is more realistic (and scientific) than that.
     
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  8. Hutan

    Hutan Moderator Staff Member

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    Well, the tweet says
    Why would they be working to block the glucocorticoid receptor if there wasn't at least a suspicion that it was a problem in people with ME/CFS?

    True. But my doubt about a mouse model extends to GWI for the same reasons - you have to have the right biological mechanism before that is of use. The tweet says that ME/CFS has no mouse model yet, but that they are in phase 1 of trying to block the glucocorticoid receptor in ME/CFS. That implies that there will be a mouse model at some time later.

    The paper says
    To be fair, the paper suggests that it is a multifactorial process. And yes, stress may be a factor in GWI.

    From the paper;
    The answer they propose includes blocking the glucocorticoid receptor.

    That's the same answer they are proposing for people with ME, even though, to me, the ME/CFS question is different. There is no good evidence that we have, on average, that same group of signs.

    It's the focus on cortisol and glucocorticoid receptors in people with ME that I have the biggest problem with. Leaping to work on glucocorticoid receptors on the basis of assumed abnormal cortisol levels and HPA axis problems is premature. I don't think that there is evidence to support abnormal cortisol levels being a widespread or diagnostically important problem in people with ME.
     
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  9. Hutan

    Hutan Moderator Staff Member

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    Here are the results from the hair cortisol study in women with CFS I gave a link to above. Does it look like women with CFS have a problem with raised cortisol like the men with GWI are supposed to have? Or indeed anything really odd with our cortisol that can't be explained by a global hypometabolism? If not, then why would the same approach of blocking the glucocorticoid receptors be helpful?

    [​IMG]

    I'm just saying, this doesn't seem to me to be the type of work that is likely to bear fruit. I'd be putting more work into defining a problem in cortisol or some other problem relevant to glucocorticoid receptors in ME/CFS before fiddling with the glucocorticoid receptors. But on the other hand, who knows what intervention will find the answer to ME/CFS and I don't know much about what else this team has done. At least they are trying something I guess.
     
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  10. adambeyoncelowe

    adambeyoncelowe Senior Member (Voting Rights)

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    I asked #MEAN what Klimas is blocking but they didn't answer, so maybe she didn't say. I don't think it's the same receptor as in GWI. I think the tweet is just ambiguously worded.

    My take away from it was that she's trying to block a different receptor for us, after identifying the GCR in GWI. I may have misunderstood, though.
     
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  11. Fungi

    Fungi Established Member

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    I am not sure I follow all of the previous messages but it sounds a little like what I was thinking.
    The symptoms for PTSD are similar to chronic fatigue. According to an article I read in Psychology today,

    https://www.psychologytoday.com/us/blog/the-aftermath-trauma/201606/cortisol-and-ptsd-part-1

    a lot of PTSD patients have lower cortisol levels (or levels that the body cannot regulate) which are often dismissed by doctors as they are not significantly lower and are still within the acceptable range yet it has very significant effects on PTSD patients. In this article, it discussed various studies which showed that if pregnant women experience a trauma, they can ‘programme’ the foetus with the result that when their children grow up, they are much more likely to develop PTSD. This is true even if other people experience the exact same trauma as them but with no effects. In utero babies are particularly sensitive to hormone fluctuations and this then predisposes their babies to be more susceptible to stress i.e. to lack resilience. So I wonder if ME patients have a biological marker whereby if they experience stress/work in high demanding areas and therefore higher levels of cortisol, the body (PTA) as a system then fails and is unable to produce even sufficient cortisol required for daily life or is unable to manage the normal daily pattern which cortisol should follow. These individuals lack the physiological resilience to cope with stress/high performance which would not affect the vast majority of the population. Many of the symptoms of chronic fatigue could be explained by even a little lower cortisol levels which medical professionals would not even register as important. What does anyone think?

    BTW what does GCR and GWI mean?
     
  12. Andy

    Andy Committee Member (& Outreach when energy allows)

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    Welcome @Fungi . I'd assume GCR means glucocorticoid receptor, GWI definitely means Gulf War Illness.
     
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  13. Hutan

    Hutan Moderator Staff Member

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    I can't see the resemblance between PTSD and ME/CFS myself (or even between PTSD and chronic fatigue - that latter presumably just being fatigue that is chronic). Here's one list of PTSD symptoms:

    Are you familiar with the symptoms of ME yourself Fungi? May I ask what your interest is in ME?

    Regarding your idea that people with ME might have a biological marker caused by their mothers experiencing trauma while they (the people with ME) were in utero:
    My mother was happy and calm when she was pregnant with me. I was happy and calm when I was pregnant with my two children. All three of us developed ME at the same time.

    Regarding your idea that people with ME might not be able to produce sufficient cortisol required for daily life:
    I don't believe that there is any good evidence for that. Do you know of some?

    So, I think you are saying that people are predisposed to ME in utero and then become ill when exposed to stress? I routinely dealt well with challenging work for many years before becoming ill. My children had normal childhoods and were not dealing with high levels of stress prior to becoming ill. If your theory was correct, then we would expect to see massive rates of ME in civilian populations exposed to long-running wars. I don't think we have evidence of that.
     
    Last edited: Nov 25, 2018
  14. Fungi

    Fungi Established Member

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    Apologies for the long post. Here are some of my meandering ideas based on the article referred to above - links here:
    An interview with Dr. Rachel Yehuda in
    https://www.psychologytoday.com/us/blog/the-aftermath-trauma/201606/cortisol-and-ptsd-part-1
    https://www.psychologytoday.com/us/blog/the-aftermath-trauma/201606/cortisol-and-ptsd-part-2
    https://www.psychologytoday.com/us/blog/the-aftermath-trauma/201606/cortisol-and-ptsd-part-3

    First of all, although I am not a scientist, I have been trying very hard to understand CFS for the last two years since my son has been affected by it, so please bear with me.

    Patients with PTSD do not show lower levels of cortisol when discharged from psychiatric wards unlike other patients. In fact patients with PTSD have significantly lower levels of cortisol at admission and discharge compared to other patients with psychiatric diagnosis. This seems counter intuitive as you would expect cortisol levels to be high in patients with stress disorders. So Dr Yehuda and Mason replicated the study and found the same lower levels of cortisol. They also observed elevated catecholamines. Apparently this is to be expected, that people who are aroused and under stress have high levels of catecholamines, like norepinephrine but lower cortisol levels were harder for people to accept. The prevailing concept was that PTSD always occurred following trauma exposure.



    Dr Yehuda talks about the idea that epigenetic changes in traumatised parents that occur as a result of their trauma exposure can be passed on to children. She gives the examples of effects in the children of holocaust survivors and in babies born to women who survived 9/11.

    So my interpretation idea is as follows:

    Working mothers may experience more stress with higher cortisol levels which the body is unable to break down into cortisone. In utero babies are particularly sensitive to hormone fluctuations and this then predisposes their babies to be more susceptible to stress or hormonal fluctuations i.e. to lack hormonal resilience. As more women have entered the labour market, many work in demanding and stressful jobs, they pass on a physiological predisposition to their offspring which means their child is physically unable to cope with stress or hormonal fluctuations i.e. they lack physiological resilience.

    This could then possibly explain the rise in mental health in young people in Britain in recent decades, what some people refer to as an epidemic of mental health. The government talks about helping to make children more resilient but that could be something built into their very DNA which external individuals would find hard to mitigate.
     
    Last edited by a moderator: Nov 28, 2018
  15. Fungi

    Fungi Established Member

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    This could then perhaps explain why some individuals are susceptible to CFS while others who experience the same events are not.

    Many CFS patients have improved only to find that they relapse again. Also, many patients when they have been ill for a number of years with chronic fatigue readjust to their new norm and may say their health is good when in fact it is just that they have adjusted to a life with a severe disability e.g. not working, living in a bubble etc . I view the person as always at risk even after they have recovered they may relapse as they have biomarkers that predispose them to trauma.


     
    Last edited by a moderator: Nov 28, 2018
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  16. Fungi

    Fungi Established Member

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    Following on from my last post, I just wonder if ME/CFC is due to the inability of the body to regulate cortisol levels a bit like diabetes is due to the body's inability to produce/regulate insulin. This could be due to an autoimmune destruction of the cortisol producing cells in the cortex of the adrenal glands. It affects lots of areas in the body such as metabolism and immune response. This would be different than Addison’s or Cushing’s disease as cortisol levels may fluctuate i.e. be too high at some point and too low at others leading to inconsistent findings or perhaps the irregular levels may not be significant enough to merit medical interventions.
     
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  17. Seven

    Seven Senior Member (Voting Rights)

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    She explained it, everytime she gave the neurotoxins ( I think it was or pesticide?)then stress them. Did that a few time and bang they have GWS (
     
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  18. Fungi

    Fungi Established Member

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    I see in this article that GWI has similar symptoms to CFS. 'GWI symptoms span several of the body’s principal regulatory systems and include debilitating fatigue, severe musculoskeletal pain, cognitive and neurological problems.'
     
  19. Fungi

    Fungi Established Member

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    A few years ago I watched a bee 'staggering' around my garden as if it was blind or blind drunk. Some time after that I heard about the negative impact of pesticides on bees that can lead to Colony Collapse Disorder and it was like a Eureka moment as it made total sense. Reading this article here explains the effects of neonicotinoid pesticides as resulting in less movement and activity from queen bees and worker bees. However, if dosage of neonicotinoid was increased there wasn't a proportional response from different honey bee colonies i.e. even less activity. In other words, some colonies were better at detoxifying than others. I wonder if something similar is going on with CFS patients; that somehow their environment is toxic to them. Do they have biological markers that make them more susceptible and less able to detoxify? I mentioned it to my son's osteopath and she said that the ME patients she treats who live near farm land are worse during spraying season. I realise this is anecdotal but interesting nonetheless.

    This links in with something else I was thinking about. There was a tragic death some time ago of a teenager who had a severe allergic reaction to sesame seeds and died while on a flight to France. Discussing allergies, they mentioned that there is often a link between childhood asthma and eczema and developing severe allergies later on. There has also been a dramatic increase in the number of people with severe allergies with around 2% of the population (if I remember correctly) having such an allergy. Again I just wondered how many CFC patients have similar issues in childhood i.e. asthma/eczema/food allergies and whether their bodies are programmed to react as if poisoned leading to systemic failure? Some can detoxify/repair themselves very slowly over a long period of time.
     

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