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!
First Direct Evidence of Neuroinflammation - 'Encephalitis' - in ME/CFS
A small study with just nine patients has captured the attention of patients and researchers alike after reporting direct evidence of inflammation in the brain of ME/CFS patients. The finding was one of the highlights picked out by Professor Anthony Komaroff in his IACFS/ME...
Discuss the article on the Forums.

New Klimas Paper- NPY, Stress, HPA Axis and CFS

Discussion in 'XMRV Research and Replication Studies' started by shannah, Dec 29, 2010.

  1. OurDayWillCome

    OurDayWillCome

    Messages:
    61
    Likes:
    0
    Willow...look at this link for the history of this field:

    http://www.nfnlp.com/psychoneuroimmunology_quinlan.htm

    An excerpt:

  2. lancelot

    lancelot Senior Member

    Messages:
    324
    Likes:
    2
    southern california
    "By conditioning the immune system through mental processes a connection in communication has been made."

    Exactly how does that work???
  3. Angela Kennedy

    Angela Kennedy *****

    Messages:
    1,026
    Likes:
    152
    Essex, UK
    Yeah, right - have you not seen the mention of causation fallacies on your journey through this thread? Do you not know THIS is a key problem in ME/CFS research? If we accusing others of 'agendas' now - what 'agenda' do YOU have?
  4. Angela Kennedy

    Angela Kennedy *****

    Messages:
    1,026
    Likes:
    152
    Essex, UK
    Well that's the interesting thing - they don't know, and may never. But fallacious special pleading around ME/CFS as a psychogenic illness (by default due to medical uncertainty, by the way) away from other organic illnesses is a key aspect of this approach, and they would rather spend time and money following what is a wild goose chase then study ME/CFS as an organic illness.
  5. Angela Kennedy

    Angela Kennedy *****

    Messages:
    1,026
    Likes:
    152
    Essex, UK
    By they, I mean governments, psychiatrists, other doctors, the MRC, etc. etc.

    Re Klimas - I've noticed a lot of scientists and doctors who people see as 'the good guys' (a way of looking at things which is misguided I think) saying things or taking part in projects which are flawed and psychobabbly. The community faces a lot of cognitive dissonance when faced with this. I would advise the community to stop looking for heroes. These people are mostly working to further careers and research interests. This means they get involved in woefully poor science authored by promoters of psychogenic explanations. I don't hink we can 'trust' Klimas to be painting a bigger picture by this project necessarily - if, by the sound of her email, she doesn't understand what might be wrong with this latest project she put her name to. So, some of us will have to critique work she's involved in - the same goes for Kerr, Weir, Newton, as just a few examples.

    I have no emotional ties to any of the scientists and doctors in this field. I don't see them as villains or heroes, just part of a flawed system, which makes it easier to critique their claims and methods when that needs to happen.
  6. Angela Kennedy

    Angela Kennedy *****

    Messages:
    1,026
    Likes:
    152
    Essex, UK
    Nice explanation Willow.

    I wish there was a 'like' function on this forum for posts like these.
  7. Enid

    Enid Senior Member

    Messages:
    3,309
    Likes:
    840
    UK
    Thank you for an interesting discussion. I quite agree anything pyschobabbly is not only erroneous but could tempt that lot back in. So much caution I feel should be given to findings and reporting in this type of research. But a biomarker (not the cause) may aid.
  8. biophile

    biophile Places I'd rather be.

    Messages:
    1,350
    Likes:
    4,116
    Slippery slope on the mountain of speculation

    The impression I receive from this paper: NPY is involved in the neurobiological stress system and associated with a range of conditions. Elevated NPY somewhat correlates with "perceived stress, anger, depression, negative thoughts and maladaptive coping" in CFS patients. There is mention of a connection between dysregulation of the immune and neurobiological stress systems, but they do not appear to speculate much about the direction of causation in regard to the psychological symptoms (others will no doubt be doing such speculating though) but they hint that elevated NPY may be due to infection, immune activation and inflammation. I have no idea if hypocortisolism would be more or less of a problem in CCC defined CFS.

    However, the lack of clarification on "symptoms" is disappointing because in the Background section text there is talk of "CFS symptoms" and "clinical symptoms", but as others have already pointed out the results focus is on psychological and psychosocial measurements. It is possible that physical symptoms help to explain the reported correlation of NPY with "general health" and "fatigue disruption rating" but these measurements are probably influenced by psychological symptoms as well. They talk about hypocortisolism in CFS, but we don't know if this actually relates to psychological symptoms and the elevated NPY, and they failed to emphasize enough that hypocortisolism is far from being a universal finding in CFS.

    It is unclear how useful or helpful a "stress related NPY elevated" subset would be, it seems problematic, especially without knowing the cause of elevated NPY, with significant overlap of NPY levels with healthy controls, and questionable relevance to CFS, as well as the usual issues with measuring or interpreting "stress". Suppose a CFS patient with normal NYP goes through a rough stressful year so their NPY and negative psychological symptoms are elevated, then the rough year is over and things returns to baseline. Are we supposed to believe that such a patient temporarily had a different subset of CFS? Suppose another patient has elevated NPY and is therefore told they fit into the "stress related" subset even if they don't feel stressed, are we supposed to believe they need stress reduction techniques anyway?

    People with temporary influenza who are otherwise healthy often appear irritable and more "vulnerable" to psychosocial stresses, probably because they feel terrible and may also have immune-mediated changes to cognitive function etc. CFS is often described as feeling like a permanent influenza, and the prolonged duration of years or even decades as opposed to mere days or weeks would have additional downstream consequences. Using that comparison, I don't have a problem with the possibility that CFS partly involves an immune-related dysregulation of neurobiological stress system which worsens the effects of the psychosocial stresses imposed on patients by the devastating effects that CFS has on their lives.

    What I am uncomfortable with is how related research and speculation typically get simplistically generalized to justify hypothetical "mind over body" mechanisms in all CFS patients by default even when the findings are far from universal and the supposed relationship with "stress" is still unclear. Hypocortisolism for example is frequently employed to help explain so-called "effort/stress intolerance" and other symptoms in CFS (eg like Van Houdenhove et al 2009 as cited by this new Fletcher/Klimas paper), but as far as I know such HPA axis abnormalities reported in the CFS literature are usually relatively mild and non-uniform, usually found in a minority of patients, don't usually exist until years into the illness, and are possibly related to reduced activity. Also note that, like elevated NPY, HPA axis disturbances are also found in infectious and auto-immune diseases, they are not restricted to so-called functional illnesses and mental disorders as some people may have you believe.

    There are so many unresolved issues relating to CFS criteria, the concept of stress, and so-called psychoneuroimmunological mechanisms, it is an interesting but extremely slippery slope which must be approached with great care.
  9. Angela Kennedy

    Angela Kennedy *****

    Messages:
    1,026
    Likes:
    152
    Essex, UK
    Thanks biophile,

    Nice analysis of the problem. I think this is indeed a 'slippery slope' issue which should be approached with great care - but currently isn't. Sadly, every piece of flawed research just adds to the edifice of psychogenic explanation, with all it's confusion of concepts and character denigration of patients.
  10. alice1

    alice1 Senior Member

    Messages:
    457
    Likes:
    0
    Toronto
    Klimas is one of several docs I see and I take everything all of them say with a grain of salt.But I would like to add that Dr Klimas is the only doctor with whom I've met over the past 24 years whose given me a straight answer to questions I ask even if she doesn't know the answer.I don't regard her as a hero nor does she ever give me the impression she sees herself as one.
    It would of been great had she written the study herself as it may have included a better interpretaion..Who knows.
  11. Cort

    Cort Phoenix Rising Founder

    Messages:
    7,025
    Likes:
    432
    Raleigh, NC
    They've looked at a variety of possible markers over the years. NPY is certainly a tenable one given the evidence of sympathetic nervous system dysregulation and its connection to other issues and to the CD26 immune marker and it some extent you have to follow the research where it leads; if its there - its there.

    When I see NPY possibly linked to immune dysregulation, POTS and autoimmune disorders - I think even better.

    I don't mind the stress connection as much - at least for me it fits at least to some degree and I recognize that it doesn't fit for other people and its a very problematic term (we seem to specialize in those) given our history. It distorts things and lessens the severity of the disorder in many peoples minds - it sucks!

    I don't fit criteria for depression or anxiety (and like many I have seem psychs in my journey with CFS) but the irritability, difficult focusing, difficulty calming down is definitely a feature of this disorder for me. So when I see a biological marker that could help explain those problems I tend to think - good!

    The NPY connection could help in an odd way because if you can carve out an NPY subset then you can then concentrate on people with different problems. ELevated NPY wasn't found in everybody and it appears to have lots of other ramifications as well - my guess is that these go hand in hand with this sympathetic nervous system arousal and as they continue to dig deeper into NPY and its connections in CFS things will blossom. I hope this is like a rough entry into a potentially valuabe area.

    One problem is that it easier to give somebody a questionnaire than to dig into their biology and that too often happens.

    I'm glad Dr. Klimas didn't write the paper; I think she would have approached it and written it differently. Ifelt the conclusions section was really not very well done - it seemed off to me....not well written, not very conclusive...:)
  12. Cort

    Cort Phoenix Rising Founder

    Messages:
    7,025
    Likes:
    432
    Raleigh, NC
    I wholeheartedly agree about not looking for hero's. Researchers have a duty to publish their results no matter what they are - which can be difficult when the results do not turn out how we want..and there goes our 'hero'.

    I think Dr. Klimas can be trusted to paint a bigger picture of this disorder. She's collaborated with Dr. Fletcher for decades and both of them have been the key figures in documenting the immune problem in this disorder - natural killer cell function. We would not have natural killer dysfunction documented if not for them. I cant think of another paper she's co-authored that has raised any concern at all.
  13. WillowJ

    WillowJ Senior Member

    Messages:
    2,903
    Likes:
    2,317
    WA, USA
    I wholeheartedly and unreservedly second the motion of trust. Dr. Klimas has untiringly looked for answers and has been finding some very good ones. When she does write the manuscripts she explains our disease quite well. Dr. Fletcher also has been working on immunological answers.
  14. OurDayWillCome

    OurDayWillCome

    Messages:
    61
    Likes:
    0
    Me too. I was... and still am... looking at the science of this. Sometimes we have to wade through the muck to find a pearl or two.

    Klimas.... I don't know enough about her personally to give her a thumbs up or down. I have some catching up to do.

    Heroes... they are like the rest of of. They have feet of clay.

    I did find this on NPY...

    I added the [antianxiety]

    http://www.nature.com/nature/journal/v452/n7190/abs/nature06858.html
  15. lancelot

    lancelot Senior Member

    Messages:
    324
    Likes:
    2
    southern california
    Dr Klimas gets a thumbs up from her overall CFS work but a thumbs down in this particular study, but always remember she is here for US. She is a good person trying to do what is right. We can help her not to get involved in bad phsycobabbly studies by criticizing this study and emailing her our objections as WillowJ has done. Dr Klimas will not make that mistake again! patient pressure and lobbying works!
  16. OurDayWillCome

    OurDayWillCome

    Messages:
    61
    Likes:
    0
    Thanks Lancelot.

    I think it might be wise to read the PDF of this paper. While it is not as strong as I would like for it to be, it does mention the possibility of NPY being elevated due to viral infection.
  17. Marty

    Marty Senior Member

    Messages:
    117
    Likes:
    17
    Quote from Lancelot: Dr Klimas gets a thumbs up from her overall CFS work but a thumbs down in this particular study.

    I agree. Come on, Klimas can't put her name on a paper and then claim she's not responsible for it.
  18. Dolphin

    Dolphin Senior Member

    Messages:
    6,543
    Likes:
    4,998
    I agree.
    We need more biology, less questionnaires. For example, in this study it would have been interesting to know whether the results correlated with other biological measures or not.

    Academic discussions are interesting. But it's biological/biomedical research that will give us the progress we want.
    For that, researchers need money. Questionnaire research can be done cheaply.
  19. Dolphin

    Dolphin Senior Member

    Messages:
    6,543
    Likes:
    4,998
    I'm not sure it is true that they only measured 3 of the 8 SF-36 subscales.
    I think "including" is the crucial word. If they were looking for just mental health measures, I would imagine they would have used both the "role emotional" and the "mental health" subscales.

    But only three of the scales are listed in those scales that had "Pearson Correlations (with p < 0.1) ... with Plasma Neuropeptide Y".

    Like oceanfree says, physical functioning and role physical are the more interesting ones in terms of physical functioning in CFS. So if they were measured but did not correlate much, then it would suggest NPY is not necessarily a good measure of SF-36 severity.

    Somebody could write to the authors to double-check.

    There is an average difference across the range of values that is not due to chance (see Table 1).

    However, no particular value has a particularly good sensitivity and specificity (one is basically looking for the largest value above the diagnonal line).
  20. Dolphin

    Dolphin Senior Member

    Messages:
    6,543
    Likes:
    4,998
    (OT?) Criteria revision

    WillowJ later:
    Contrast this with the sleight of hand in the Reeves et al, 2005 paper:
    Reeves WC, Wagner D, Nisenbaum R, Jones JF, Gurbaxani B, Solomon L, Papanicolaou DA, Unger ER, Vernon SD, Heim C. Chronic fatigue syndrome--a clinically empirical approach to its definition and study.
    BMC Med. 2005 Dec 15;3:19.
    http://www.biomedcentral.com/1741-7015/3/19
    * that's the Reeves et al, 2003 paper.

    Why would he and the others not even follow their own paper?
    I think it was to be able include more of these people who previously had MDDm i.e. not a good reason.
    The specific reason I think was the following: when they took in the people who they had followed from 1997-2000 in 2003 (note: papers weren't published till 2005 on) for a barrage of testing, they found they had few CFS cases (10-16), out of the 227 people they invited in. They did all sorts of fancy tests on these people (the exercise cost $2m from what I hear) but it was going to be difficult to produce CFS papers especially as some patients were being excluded for one reason or another from some tests e.g. were on medications, problem with sample, they were male, etc. It would be a scandal if they didn't produce CFS after spending that amount of money from the CFS budget. The CDC CFS program had already gotten into trouble with Congress for not spending some of its allocation on CFS research.
    Increase the number of people with CFS by broadening the definition and there is suddenly no problem about not having enough CFS cases.

See more popular forum discussions.

Share This Page