1. Patients launch $1.27 million crowdfunding campaign for ME/CFS gut microbiome study.
    Check out the website, Facebook and Twitter. Join in donate and spread the word!
Join the National PR Campaign for ME: Power to the Patient (P2tP)
Have you had enough of all the neglect and abuse of ME/CFS patients? Gabby Klein says now is the time for a National PR Campaign for ME/CFS to impress a change. Join the Patient Revolution to restore power to ME patients ...
Discuss the article on the Forums.

Possible Genetic Dysregulation in Pediatric CFS - Jason, Mikovits et. al.

Discussion in 'Latest ME/CFS Research' started by Snow Leopard, Dec 12, 2010.

  1. Snow Leopard

    Snow Leopard Senior Member

    Messages:
    2,367
    Likes:
    1,946
    Australia
    I did a quick search and couldn't find a discussion on this one.

    http://www.scirp.org/journal/PaperInformation.aspx?paperID=3046&JournalID=148
    PDF: http://www.scirp.org/journal/PaperDownload.aspx?FileName=Psych.20100400004_58674684.pdf&paperID=3046
     
  2. WillowJ

    WillowJ Senior Member

    Messages:
    3,099
    Likes:
    2,716
    WA, USA
    Jason's team working with Mikovits, that I'd like to read... thanks, Snow
     
  3. WillowJ

    WillowJ Senior Member

    Messages:
    3,099
    Likes:
    2,716
    WA, USA
    1) why on earth are they citing Rajeevan et al.'s glucocorticoid study as if Reeves disease had some relevance?? These scientists know better than that :confused: Maybe because of NAID grant? ... other bogus citations :headdesk: :headdesk: :confused: ... and a few fine citations...

    Ok, big deal over small potatoes, it's the introduction, I know. They're supposed to cite the other literature. But...

    2) ok, that's amusing... they define apoptosis for their audience? or did they know a lay audience would be reading and do it for their benefit? (question for those with no training in higher science: does "programmed cell death" mean anything to you anyway?)

    3) wait, they did not characterize their CFS population, other than location, age, and race. No definition, no length of time ill, no level of disability, no presence/absence of depression, no nothing.

    4) they did not characterize the control group, either, except to mention that it was pediatric. Not even location, age, and race. No presence or absence of fatigue (we really should be using other fatiguing medical disease plus healthy persons as dual controls, to check what things are unique to ME and what things go along with chronic disease in general), no nothing.

    5) the causative possibilities are multiple but they do include infections, lack heat shock protein (Hsp, a cell repair protein; lack of certain types of Hsp has been found by Jammes et al. and Thambirajah et al.), and oxidative damage.
     
  4. Snow Leopard

    Snow Leopard Senior Member

    Messages:
    2,367
    Likes:
    1,946
    Australia
    Well I'm skeptical of the 'neuroendocrine' model of CFS in general, but I thought I'd post this study here for you guys anyway.

    An age range for the pediatric (control) samples was given - 6-16.

    Most of the studies that I have read measuring salivary cortisol (or serum for that matter) have methodological deficiencies (samples must be taken on days of rest - Saturdays for controls, several samples must be taken over the first hour so that proper compliance can be demonstrated). Such studies should also use individuals with other chronic diseases with similar activity patterns as controls.
    Otherwise low cortisol and glucocorticoid gene expression could have a much simpler explanation - CFS patients lead lower stress lifestyles (due to low activity, no school/employment etc).

    It is possible that this model may only explain the symptoms of a subset of patients - you can't analyse the distribution with such a small sample though.

    The hypothetical mechanisms discussed however are interesting.

    This appears to be Sorenson's work:
    http://las.depaul.edu/nursing/People/FulltimeFaculty/MatthewSorrenson.asp
     
  5. Dolphin

    Dolphin Senior Member

    Messages:
    6,824
    Likes:
    5,934
    I wasn't pleased to see that reference either [or reference 11 which is actually the same data set (Wichita 2-day study) which was analysed by different groups]. But at least this study investigated the issue - it didn't really depend on that reference (like a literature review might).

    I stopped studying biology aged 16. I find it useful when researchers give just enough information that somebody without higher training might be able to understand a paper or at least the rationale. I find I can get the jist of lots of papers without fully understanding the biological systems involved.

    I have come across the concept of apotosis a few times over the years. But don't mind a little reminder about what it is (which can remind me of a something a little more detailed I read).
     
  6. Dolphin

    Dolphin Senior Member

    Messages:
    6,824
    Likes:
    5,934
    Yes, good to post what is coming out. It's certainly of some interest given the authors. Even if studies themselves aren't always of that much interest to me, it can be interesting to see what direction authors are going, theories they have, etc. from papers.

    Just to be clear, you're talking about the controls.
    Good point.

    I have been sceptical of neuroendocrine models in the past. However, it is interesting that some studies have suggested they can be useful to predict responses to nonpharmacological trials.

    Of course, other things can predict outcomes also:
    Also, I have seen at least one person rush to say she didn't think she had abnormalities in this area because of one saliva test. I wouldn't be convinced that would be enough. Also, average differences don't show up comparing one sample with norms e.g. women could be less tall than men but many women would still be in a 95% C.I. of male heights.
     
  7. Snow Leopard

    Snow Leopard Senior Member

    Messages:
    2,367
    Likes:
    1,946
    Australia
    How about this:

    Those with more severe symptoms have reduced activity levels.
    Those with more severe symptoms are less likely to have successful outcomes from non-pharmacologic treatments.
    Activity levels are correlated with salivary and serum cortisol levels. (at least in healthy patients, according to various papers)

    Therefore....

    Although I agree there is still the possibility that there might be a subset of CFS patients with Addison's-like pathology. It would be interesting to map the distributions of the low cortisol measurements.

    I'm just starting to read "The Associations Between Basal Salivary Cortisol and Illness Symptomatology in Chronic Fatigue Syndrome - Torres-Harding et al." now and they cite Hessen et al who found that low cortisol levels were correlated with cognitive impairment in 15 MS patients.

    At best, I think the low cortisol (but not ultra-low, such as Addison's disease) findings are nonspecific and associated with chronic disease and lower activity levels in general.
     
  8. ukxmrv

    ukxmrv Senior Member

    Messages:
    3,508
    Likes:
    2,041
    London
    Snow Leopard,

    I had salivary cortisol levels taken when working part time and when much worse and not working at all (both with ME but at different times/years). I've also had it taken in hospital twice as a blood test. They were all low and about the same overall when compared to a range.

    Low cortisol in CFS was also reported by Demitrack. There is no evidence that in patients with CFS the low cortisol is related to low activity.

    It could also be argued that PWCFS have more stressful lives due to benefit cuts, money worries, family problems over the disease etc.

    XMRV+
     
  9. Snow Leopard

    Snow Leopard Senior Member

    Messages:
    2,367
    Likes:
    1,946
    Australia
    Lots of things can be argued of course.
    I'm pointing out that there are other explanations for the data. I'm especially skeptical of the adrenal burnout hypothesis (which is suggested as the cause for the low cortisol response) which is part of a so-called biopsychosocial model promoted by certain psychiatrists.

    The fact is that there is already significant debate in the literature over the pitfalls of the various cortisol measurements. There is also significant evidence to support the idea that cortisol levels are related to activity levels (activities that cause stress presumably) and employment, at least in healthy individuals.

    BTW, it is hard to draw conclusions from a study with n=1, because there can be many confounding factors. ;)
     
  10. Dolphin

    Dolphin Senior Member

    Messages:
    6,824
    Likes:
    5,934
    It would be interesting if there were more scans of adrenal glands. People may recall the small study by Ted Dinan and others:

    It would be interesting to see how consistent this finding was within people. I know one person (not me) who contacted Ted Dinan - TD said he thought that the adrenals had perhaps been overactive initially and had worn out/atrophied i.e. suggesting it was more permanent.

    I, of course as a patient, don't like to hear about "permanent damage" so hope changes aren't permanent.
     
  11. Snow Leopard

    Snow Leopard Senior Member

    Messages:
    2,367
    Likes:
    1,946
    Australia
    Permanent damage doesn't mean untreatable pharmacologically though. It is speculative to suggest that it is due to atrophy, it would be interesting to see the effect of length of illness on the observations - or any changes after recovery!

    Note that:
    The sample was a CFS subset, 8 of 52 referrals, 40 of which had a CFS diagnosis.
    That study "The low dose ACTH test in chronic fatigue syndrome and in health" states that:
    Those two healthy subjects were both men.
    There is also the usual discussion that sampling times, intervals affect results.

    Imaging studies require normalization procedures and I'm not sure what they were, since I don't have access to the Vincent 1994 Normal gland size study.

    The study also states
    So enlargement during anxiety and stress and shrinkage during ????.

    But then we also have:
    http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2265.1999.00856.x/full
    (no response to low dose ACTH)

    BTW, A local group here is planning on doing a longitudinal MRI imaging study on women with post-EBV fatigue. I think they also have an article in JMRI coming out in January?
     
  12. ukxmrv

    ukxmrv Senior Member

    Messages:
    3,508
    Likes:
    2,041
    London
    Snow leopard,

    I'm also sceptical about the adrenal burnout theory around CFS and cortisol levels. There is no evidence that PWCFS have high cortisol before their illness or at any time in it. The only patients with high cortisol (as per depression) are Simon Wessely's and Demitrack commented at the time how different this was.
     
  13. WillowJ

    WillowJ Senior Member

    Messages:
    3,099
    Likes:
    2,716
    WA, USA
    I'm skeptical of the cortisol-causative and adrenal-burnout theories, too, except as possibly subsets.
     
  14. WillowJ

    WillowJ Senior Member

    Messages:
    3,099
    Likes:
    2,716
    WA, USA
    right on the first count

    on the secont point, I'm glad it was useful. I imagine they know a lay audience is reading these papers. :)
     
  15. Dolphin

    Dolphin Senior Member

    Messages:
    6,824
    Likes:
    5,934
    Another example might be mitosis vs meiosis - if they put in a few little reminders now and again, it can be useful. It probably helped that in this case a lot of the authors aren't biologists.
     
  16. Cort

    Cort Phoenix Rising Founder

    Messages:
    7,025
    Likes:
    441
    Raleigh, NC
    My guess is that cortisol is a secondary player that does, nonetheless, effect immune functioning. I don't know how mildly low cortisol levels can produce a horrendous effect....If the receptors aren't working well - perhaps its possible....but it seems like a stretch..
     

See more popular forum discussions.

Share This Page