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Metabolite-Detecting Gene Expression After Exercise in CFS, MS, and Controls

Discussion in 'Latest ME/CFS Research' started by CBS, Jan 3, 2012.

  1. oceanblue

    oceanblue Senior Member

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    MF, PF and pain were chosen by the authors as they were focusing on pain and fatigue perception. It's possible that symptoms are delayed, but note that MF, PF and pain correlated with gene expression in the larger 2011 paper, which is why it bothered me they didn't in this paper. It's the correlation between biological changes and symptoms that made the first paper so compelling.
     
  2. Dolphin

    Dolphin Senior Member

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    Thanks Oceanblue.

    It was a pity they had a few patients overlapping from another study. I wonder why they did that.

    I don't believe there was any discussion or investigation of this finding which would have been interesting:

    from:
    I suppose this is the problem when one publishes papers close together and one isn't sure that one will definitely be published before another paper is published.
    I'm guessing this happens more in other fields where researchers can be more prolific.
     
  3. oceanblue

    oceanblue Senior Member

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    That's a good idea, and would provide some quantative data on how well matched the patients are. In practice, it may be very difficult to find healthy controls that are truly matched to CFS patients, unless those pateints are mildly affected, in which case there may be questions about how appicable the findings are to more severly affected patients. That's why I'd like to see exertion matched on RPE between controls and patients (so long as the RPE was set at a level that would normally cause PEM etc to patients). Another possibility is to use activity-matched patients with a different illness. MDD would be particularly interesting as their inactiity is presumably linked to motivation rather than underlying pathology.

    Of course, it's also what they were trying to do with the fatigued MS controls; actometer data would have been helpful to establish if activity levels were indeed comparable (the disability scale information they provided suggested these patients might have been quite active, but we don't know for sure). It's a pity that the difference between MS and CFS wasn't more clear cut (adrenergic the same for both and different from controls, metabolite-sensing different between CFS and MS).

    Now that would be a very interesting study.
     
  4. oceanblue

    oceanblue Senior Member

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    The overlap was with the 2009 pilot. They didn't explicitly say there was no overlap with larger the 2011(e)/2012 paper; if I was them I wouldn't have left any patients out of that study to get the sample size as big as possible - so perhaps patients overlapped wtih that one too. I think all of the patients in this MS study were tested well before the other paper came out:
     
  5. Dolphin

    Dolphin Senior Member

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    I contacted the authors. I was told the legend for figure 1 is black circle = pain; open triangle = mental fatigue; solid triangle = physical fatigue.
     
  6. oceanblue

    oceanblue Senior Member

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    This was based on some earlier comments by Cort and Alan Light, but it seems from Cort's NIH 2012 Review that I got that wrong and bigger studies are underway, though probably not with MS patients:
     
  7. Bob

    Bob

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    Cort Johnson has a new article that discusses and interprets the Lights' 2012 paper...

    A “Fatigue” Disorder No More? – What Multiple Sclerosis Taught Us About Fatigue and Chronic Fatigue Syndrome
    By Cort Johnson
    November 6, 2014
    http://www.cortjohnson.org/blog/201...sclerosis-taught-us-chronic-fatigue-syndrome/


    Some thought provoking & interesting excerpts...

    "The expression levels of two genes (P2X4/TRPVI) that bounced up immediately after exercise in the ME/CFS group, and then stayed elevated for 48 hours were associated with post-exertional malaise. One of them, P2X4, was directly associated with both the increased fatigue and pain experienced after exercise in the ME/CFS patients. These are muscle metabolite sensing genes that assess the levels of factors associated with muscle fatigue and damage."

    "Despite their enormous fatigue, the MS patients mostly sailed through the exercise period. Their physical and mental fatigue did rise 8 hours after exercise, but both was back to baseline at 24 and 48 hours. At no point did exercise increase their pain levels. The Chronic Fatigue Syndrome patients, on the other hand, immediately experienced increased levels of physical and mental fatigue and pain after exercise – which were still present 8, 24 and even 48 hours later."

    "After exercise the MS patients looked more like healthy controls than the ME/CFS patients. The levels of the metabolite sensing genes actually dropped in both the MS and healthy controls eight hours after exercise and then rebounded to normal levels. The Lights called this response evidence of a “well-regulated sensory pathway”."

    "The Lights suggested that even normal levels of muscle metabolites may be sparking an overexpression of metabolite sensing genes in people with ME/CFS. Those genes are there to alert the central nervous system that the muscles are overworked and that it’s time to induce fatigue and pain to keep them from being injured."



    Just for handy reference, these are the details of the paper...

    Differences in metabolite-detecting, adrenergic, and immune gene expression following moderate exercise in chronic fatigue syndrome, multiple sclerosis and healthy controls
    Andrea T. White, Ph.D., Alan R. Light, Ph.D., Ronald W. Hughen, Timothy A.VanHaitsma, M.S., and Kathleen C. Light, Ph.D.
    Psychosom Med. 2012 January ; 74(1): 46–54.
    doi:10.1097/PSY.0b013e31824152ed.
    http://journals.lww.com/psychosomat...s_in_Metabolite_Detecting,_Adrenergic,.9.aspx


    And, for reference, these are some of the Lights' similar papers:

    Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome, and Fibromyalgia Syndrome.
    Light AR, Bateman L, Jo D, Hughen RW, Vanhaitsma TA, White AT, Light KC
    J Intern Med. 2011 May 26.
    doi: 10.1111/j.1365-2796.2011.02405.x.
    [Epub ahead of print]
    26 May 2011
    http://www.ncbi.nlm.nih.gov/pubmed/21615807
    http://forums.phoenixrising.me/inde...seline-and-following-moderate-exercise.10638/

    Genetics and Gene Expression Involving Stress and Distress Pathways in Fibromyalgia with and without Comorbid Chronic Fatigue Syndrome
    Kathleen C. Light, Andrea T. White, Scott Tadler, Eli Iacob, and Alan R. Light
    Pain Research and Treatment
    Volume 2012 (2012), Article ID 427869
    http://dx.doi.org/10.1155/2012/427869
    http://forums.phoenixrising.me/index.php?threads/kathleen-light-new-fibro-me-cfs-review.13857/
     
    Marco likes this.

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