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Keech, Lloyd et al: Gene expression in response to exercise in patients with CFS

Discussion in 'Latest ME/CFS Research' started by mango, Sep 13, 2016.

  1. mango

    mango Senior Member

    Gene expression in response to exercise in patients with chronic fatigue syndrome: a pilot study.

    Andrew Keech1*, Ute Vollmer-Conna2, Benjamin K. Barry1, 4 and Andrew R. Lloyd3

    1 School of Medical Sciences, University of New South Wales, Australia
    2 School of Psychiatry, University of New South Wales, Australia
    3 Inflammation and Infection Research Centre, University of New South Wales, Australia
    4 Neuroscience Research Australia, Australia

    Front. Physiol. | doi: 10.3389/fphys.2016.00421

    Chronic fatigue syndrome (CFS) is a debilitating disorder of unknown pathogenesis, characterised by fatigue, which is exacerbated after minimal exercise.

    We examined the effect of a single bout of aerobic exercise on leucocyte mRNA expression of genes putatively linked to exaggerated afferent signalling as an under-pinning of the fatigue state.

    A carefully-characterised sample of patients with CFS (N = 10) and healthy matched control participants (N = 12) were included.

    Participant ratings of fatigue and other symptoms, as well as blood samples, were obtained at baseline, and five other time-points up to 72 hours after 25 minutes of moderate-intensity cycling exercise. Leucocyte mRNA of 19 metabolite-sensing, adrenergic, immune and neurotransmission genes was examined using quantitative polymerase chain reaction.

    Patients with CFS reported substantial fatigue, functional impairment and poor sleep at baseline (all p < 0.02), and exercise immediately induced worsened patients’ fatigue (effect size, ES = 1.17).

    There were no significant changes in gene expression after exercise and patients did not differ from control participants at any time point.

    Higher levels of expression of ficolin (FCN1) and a purinergic receptor (P2RX4) in patients with CFS were found when all time points were combined.

    Patients with CFS did not show significant exercise-induced changes in leucocyte mRNA of 19 metabolite-sensing, adrenergic, immune and neurotransmission genes despite a prominent exacerbation of fatigue.

    Keywords: mRNA, Pathogenesis, Myalgic encephalomyelitis, Post-exertional Malaise, Central sensitisation

    Citation: Keech A, Vollmer-Conna U, Barry BK and Lloyd AR (2016). Gene expression in response to exercise in patients with chronic fatigue syndrome: a pilot study.. Front. Physiol. 7:421. doi: 10.3389/fphys.2016.00421

    Received: 07 Jul 2016; Accepted: 06 Sep 2016.

    Edited by:
    Elisabeth Lambert, Baker IDI Heart and Diabetes Institute, Australia

    Reviewed by:
    Urs Nater, University of Marburg, Germany
    Maureen Hanson, Cornell University, USA
  2. trishrhymes

    trishrhymes Senior Member

    My first reaction to this is that the patients must have had very very mild ME. Even when I had mild ME and was still able to work part time, I couldn't have done 25 minutes of 'moderate intensity cycling exercise'. Now, at the housebound stage all this elicits is a hollow laugh.
    Jan, AndyPandy, actup and 6 others like this.
  3. alex3619

    alex3619 Senior Member

    Logan, Queensland, Australia
    Tiny study, no separation of short and long term patients, and what genes were analyzed? If I can get some rest I might look into this more later, but its not on my list of priorities.
    actup, Solstice, Hutan and 3 others like this.
  4. Cheshire

    Cheshire Senior Member

    Given the very bad methodology of Lloyd's other study (subjective outcomes and no control group, the way he dismissed the 2 days CPET test (oh, they are not making enough effort, I don't give a shit about the respitory exchange ratio), I wouldn't trust any of his studies.

    I really don't understand his trajectory, beguinning with the Dubbo study and ending with this...
    actup, ryan31337, Solstice and 6 others like this.
  5. Chezboo

    Chezboo NOT MY BOARD

    I'm just dying to know what 'a carefully-characterised sample of patients with CFS' is. Literally on the edge of my seat, does anyone know?
    AndyPandy, actup, Solstice and 2 others like this.
  6. Sidereal

    Sidereal Senior Member

    It's Lloyd, what else could you expect.
    actup, halcyon, Solstice and 3 others like this.
  7. *GG*

    *GG* senior member

    Concord, NH
    I did the 2 day CPET test in 2010, was found Moderate, 60% of what someone my age and sex should be able to do. I am not sure what Moderate intensity cycling would mean, I probably do it though, and can do more than 25 minutes now. I rest for the following day or 2, I feel worse, but it does give me some normalcy to my life. Not sure what I would do without it.

    I have exercise throughout my illness, except for 1 year, when I crashed really hard.


    Edit, not sure how they selected patients :(
    Last edited: Sep 14, 2016
  8. snowathlete


    Yeah, I was moderate at the point where 5 minutes of low intensity exercise on the lowest setting, was enough to cause me to crash and become severe. So these guys doing moderate intensity for 25 minutes suggests they were mild. Also, such a small study makes it difficult to conclude anything meaningful.
    actup, Sidereal and trishrhymes like this.
  9. M Paine

    M Paine Senior Member

    Auckland, New Zealand
    I like it. They cast a relatively wide net (leucocytes) with a set of very specific hooks (mRNA of 19 metabolite-sensing, adrenergic, immune and neurotransmission genes using PCR).

    It would be interesting to know what genes were targeted, clearly they focused on certain candidates. This looks like a gene expression paper on a tight budget. One of these days, a gene expression paper is going to hit the mark.
    actup, GreyOwl and Hutan like this.
  10. Hutan

    Hutan Senior Member

    New Zealand
    Ficolins - from wikipedia:
    P2RX4 from Wikipedia
    I'd be interested to hear what the authors of this study made of the higher levels of expression of FCN1 and P2RX4. And what others (perhaps not so firmly attached to a central sensitisation theory?) might make of it.

    At least we know Maureen Hanson is aware of the finding - so, if it helps build a helpful theory, I'm sure she will make use of it.
    actup likes this.
  11. halcyon

    halcyon Senior Member

    Looks like they used the healthiest, most unaffected Fukuda patients they could get their hands on.

    Basically they failed to replicate Light et al. 2012 which is pretty disappointing. Probably important to note that in Light's study (which also used Fukuda), 96% of the patients also met CCC.

    You'd think if you were doing a study looking at PEM that you'd at least use a criteria that requires it, rather than one where it's optional. But Lloyd is involved, so no surprises here.
    actup, Hutan, Chezboo and 1 other person like this.
  12. *GG*

    *GG* senior member

    Concord, NH
    Ugh, that sucks!

    Guess they were not Truly trying to replicate the study :(

  13. AndyPandy

    AndyPandy Making the most of it

    25 minutes of cycling? The stuff of my dreams.
    halcyon likes this.

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