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How Stress Influences Disease: Study Reveals Inflammation as the Culprit

Discussion in 'Other Health News and Research' started by Waverunner, Apr 3, 2012.

  1. Waverunner

    Waverunner Senior Member

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    Chronic stress seems to reduce tissue sensitivity to cortisol and as a consequence the immune system loses its ability to control inflammatory processes. ME/CFS is not caused by stress but I'm quite sure that inflammatory processes play a role. The argument could work the other way round as well (inflammation leading to stress). Moreover it's interesting that they infected adults with a cold virus for this study, I always thought that these kind of human trials are forbidden.

    http://www.sciencedaily.com/releases/2012/04/120402162546.htm

    ScienceDaily (Apr. 2, 2012) Stress wreaks havoc on the mind and body. For example, psychological stress is associated with greater risk for depression, heart disease and infectious diseases. But, until now, it has not been clear exactly how stress influences disease and health.

    A research team led by Carnegie Mellon University's Sheldon Cohen has found that chronic psychological stress is associated with the body losing its ability to regulate the inflammatory response. Published in the Proceedings of the National Academy of Sciences, the research shows for the first time that the effects of psychological stress on the body's ability to regulate inflammation can promote the development and progression of disease.
    "Inflammation is partly regulated by the hormone cortisol and when cortisol is not allowed to serve this function, inflammation can get out of control," said Cohen, the Robert E. Doherty Professor of Psychology within CMU's Dietrich College of Humanities and Social Sciences.
    Cohen argued that prolonged stress alters the effectiveness of cortisol to regulate the inflammatory response because it decreases tissue sensitivity to the hormone. Specifically, immune cells become insensitive to cortisol's regulatory effect. In turn, runaway inflammation is thought to promote the development and progression of many diseases.
    Cohen, whose groundbreaking early work showed that people suffering from psychological stress are more susceptible to developing common colds, used the common cold as the model for testing his theory. With the common cold, symptoms are not caused by the virus -- they are instead a "side effect" of the inflammatory response that is triggered as part of the body's effort to fight infection. The greater the body's inflammatory response to the virus, the greater is the likelihood of experiencing the symptoms of a cold.
    In Cohen's first study, after completing an intensive stress interview, 276 healthy adults were exposed to a virus that causes the common cold and monitored in quarantine for five days for signs of infection and illness. Here, Cohen found that experiencing a prolonged stressful event was associated with the inability of immune cells to respond to hormonal signals that normally regulate inflammation. In turn, those with the inability to regulate the inflammatory response were more likely to develop colds when exposed to the virus.
    In the second study, 79 healthy participants were assessed for their ability to regulate the inflammatory response and then exposed to a cold virus and monitored for the production of pro-inflammatory cytokines, the chemical messengers that trigger inflammation. He found that those who were less able to regulate the inflammatory response as assessed before being exposed to the virus produced more of these inflammation-inducing chemical messengers when they were infected.
    "The immune system's ability to regulate inflammation predicts who will develop a cold, but more importantly it provides an explanation of how stress can promote disease," Cohen said. "When under stress, cells of the immune system are unable to respond to hormonal control, and consequently, produce levels of inflammation that promote disease. Because inflammation plays a role in many diseases such as cardiovascular, asthma and autoimmune disorders, this model suggests why stress impacts them as well."
    He added, "Knowing this is important for identifying which diseases may be influenced by stress and for preventing disease in chronically stressed people."
    In addition to Cohen, the research team included CMU's Denise Janicki-Deverts, research psychologist; Children's Hospital of Pittsburgh's William J. Doyle; University of British Columbia's Gregory E. Miller; University of Pittsburgh School of Medicine's Bruce S. Rabin and Ellen Frank; and the University of Virginia Health Sciences Center's Ronald B. Turner.
    The National Center for Complementary and Alternative Medicine, National Institute of Mental Health, National Heart, Lung and Blood Institute and the MacArthur Foundation Research Network on Socioeconomic Status and Health funded this research.
     
    fla, Calathea and Firestormm like this.
  2. maryb

    maryb iherb code TAK122

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    Very interesting study thanks for posting it. Makes so much sense with regards to ME. People report becoming ill after lots of different body stressors, operations, dental treatment, viral onset etc.
     
  3. Waverunner

    Waverunner Senior Member

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    I agree and hope that someone puts this mosaic together soon.
     
  4. Enid

    Enid Senior Member

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    Any measures for so called psychological distress ??
     
  5. floydguy

    floydguy Senior Member

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    Or definitions of "stress". Unfortunately, I see this as part of the mind body narrative. When things are not defined or measured this allows people to make up whatever they want, ie people with ME are unable to hack the real world, they are too stressed to deal...
     
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  6. Firestormm

    Firestormm Guest

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    I have to say I 'like' this research. Full paper is free: Chronic stress, glucocorticoid receptor resistance,
    inflammation, and disease risk http://www.pnas.org/content/early/2012/03/26/1118355109.full.pdf html

    'GCR refers to a decrease in the sensitivity of immune cells to glucocorticoid hormones that normally terminate the inflammatory response (69). Evidence for GCR in response to chronic stress has been found in parents of children with cancer (10), spouses of brain-cancer patients (11) and in persons reporting high levels of loneliness (5). Without sufficient glucocorticoid regulation, the duration and/or intensity of the inflammatory response increases, heightening risk for acute exacerbations such as occur in asthma and autoimmune diseases, as well as for the onset and progression of chronic inflammatory diseases such as CVD, and type II diabetes (12).'

    So while I can apply - in my case - this to the onset of my journey into hell i.e. with a viral infection I can see how repeated and protracted psychological stress could very much have played a part. But as the above infers (I haven't yet read the whole paper) a chronic medical condition can in itself be the 'stress'.

    If similar studies are completed for say, ME, MS, Parkinson's etc. it would be interesting to see the role that cortisol plays - or rather doesn't - in regulating (or not) this inflammation.

    I do have a question: Does this 'inflammation' in anyway relate to the inflammation implied in Encephalomyelitis? I know it is a general term but could it be included - although if it were then it would presumably also apply to other conditions and circumstances too. So maybe it isn't something that would 'define' our condition but would perhaps play a role in prolonging it?
     
  7. Valentijn

    Valentijn Activity Level: 3

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    Are you saying that you think ME may be perpetuated by stress or other psychological factors?

    Because that would imply that those of us that think we have a solely physiological problem are suffering from a false illness belief, and that changes in our cognition and/or behavior could result in ME disappearing.
     
  8. adreno

    adreno 3% neanderthal

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    No, it wouldn't. Your beliefs don't change glucocorticoid receptor sensitivity. And what's not physiological about HPA axis and immune system interrelations?
     
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  9. biophile

    biophile Places I'd rather be.

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    Valentijn has a point about how this research may be (mis)applied, because sooner or later someone will claim that the effects of psychological stress on the immune system can be avoided or reduced with a better attitude or whatever. It does make sense that psychological stress can contribute to the development of diseases via neuro-endo-immune mechanisms, but the effects are usually oversimplified and exaggerated by mind over body apologists. Also, it seems that once the diseases in question take hold, stress reduction isn't going to resolve the disease, at best it will help prevent further relapses or progression.

    Difficulties defining and measuring psychological stress aside, it is surprising to learn that there is seemingly more research "evidence" for the role of psychological stress in multiple sclerosis than there is for CFS (see http://www.ncbi.nlm.nih.gov/pubmed/15033880 and http://www.ncbi.nlm.nih.gov/pubmed/21335982 for example), the difference is that people do not generally blame MS patients for it even if it is true, whereas such effects reported in CFS from flawed research usually results in feverish mind over body evangelism being screamed condescendingly from the top of mountains of psychobabble.

    There are two recent systematic reviews which suggest the effect of psychological stress on the (symptoms of the) common cold is rather small (see http://www.ncbi.nlm.nih.gov/pubmed/20074403 and http://www.ncbi.nlm.nih.gov/pubmed/20716708), and without disease-specific epidemiological studies to parallel research like Cohen et al's work featured in the above ScienceDaily article, we won't really know how much effect the "decrease in the sensitivity of immune cells to glucocorticoid hormones that normally terminate the inflammatory response" etc actually has on the diseases in question. Until then it is just another potential mechanism.

    Another complication in the debate is the direction of causation. People with pre-existing biological vulnerabilities or diseases in the early stages before obvious symptoms manifest, may be more likely to report psychological stress or be less physiologically equipped to deal with external stressors, and such biological vulnerabilities would help to explain why two people can go through the same level of stress with similar attitudes but only one ends up with a so-called "stress-related illness"/disease.
     
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  10. Googsta

    Googsta Doing Well

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    It is quite interesting. In my own case I have not always had psychological stress as a factor before a relapse or indeed the intial onset.

    But most definately physical stress.
    I know many other young people also experienced the same thing, they were enjoying their sports etc when the disease hit like a bolt of lightning.
    I would love to see more studies/research done on the physical stress young people place their bodies under & it's connection to infammation & M.E.
     
  11. Firestormm

    Firestormm Guest

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    I can't add anymore than adreno said below, but chronic conditions are I believe of themselves 'stress' inducing. I need to look at the paper, but I understand it talks about cytokines and cell inflammation. It focuses primarily on a viral infection - a cold - but imagine if similar studies were conducted on say HIV or some other permanent viral infection.

    Then let's consider long-term chronic conditions of the neurological kind, like MS, Parkinsons and ME. I won't deny that my 13 years of this condition - the ups and downs, the fluctuations etc. etc. - have been incredibly stressful psychologically; BUT there is a massive component due to physical stress - the limitations on my life, the disability, the motor function and cognition.

    These effects I would suggest can and do combine to prolong this cell inflammation and restrict cortisol response. But as the study was only directed primarily at 'a cold' it is perhaps wrong to apply the same theory to our condition or any other (albeit autoimmune and other medical conditions are mentioned).

    Perhaps also consider those patients who are able to engage in the more 'relaxing' pursuits like - I don't know - Mindfulness or something or can adapt their lives to suit the needs of the condition; wouldn't it be interesting to see if they are able to lower this inflammatory response? I think it might.

     
  12. biophile

    biophile Places I'd rather be.

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    I agree that chronic diseases are stress inducing, mentally and physically. Perhaps the disease itself can trigger the stress response more directly than conscious stress and physical activity/limitations do. I wonder if chronic diseases which respond particularly negatively to stress could to some limited extent be perpetuating themselves biologically, especially the ones with pathophysiological mechanisms involving the immune system, HPA-axis, autonomic nervous system, and oxidative stress? I hope that was not too much biobabble!
     
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  13. Waverunner

    Waverunner Senior Member

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    I've been asking myself this question over and over again and I'm quite confident that it actually is that way.
     
  14. Firestormm

    Firestormm Guest

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    I hadn't been able to read your previous comment before I posted a reply to Valentijin above.

    I have read through the paper in full now although I have to say I did it pretty quickly. I think the point trying to be made is that 'stress' equates with prolonged inflammation in the case of 'a cold'. However, I am not (get me) particularly happy with the thoroughness of the study.

    It may be that in my haste I have missed some key parts, but for instance, they don't appear to have concluded that 'stress' actually prolongs the disease i.e. the length of time a person is a) infected or b) suffering. And I am not sure they have looked very closely (or closely enough) at the depth of suffering either.

    But, maybe one can still look at 'glucocorticoid receptor resistance (GCR) that, in turn, results in failure to downregulate inflammatory response' in patients who develop PVFS or ME after a definite viral infection, in a similar fashion.

    Of course none of this is any good I don't suppose unless there is a treatment at the end of it all. Whilst resting (Ha!) this afternoon I did think that maybe these tests could form the basis for checking the effectiveness of CBT or even GET on such patients!! :D

    Simply check levels of inflammatory response before a session of CBT/GET and then check them after (I'm only partially kidding). It might provide some more objective measure to said 'treatments' after all.

    I think I need to better read the paper (sigh). I tell you, reading and following all the research could become a full time job - one which I clearly cannot manage: talk about 'stress' :D
     
  15. Calathea

    Calathea Darkness therapy

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    Anecdotally, I know a forum for adult children of narcissists where they report that a very high proportion of members have ME, and come to that other medical conditions too. Bring brought up by an abusive parent is enormously stressful, it goes on for a long time, and I wouldn't be at all surprised if it messes with your immune system.
     
  16. Snow Leopard

    Snow Leopard Senior Member

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    The problem with this paper is the same with the preceding papers on the topic, the systematic regulation between cortisol, GCR, ACTH, cytokines etc is unknown. To improve our existing models (which are far too simplistic - eg 3 variable models and they don't properly explain the low cortisol and low GCR findings in CFS), we need to measure all variables in the same patients, comparing within patient differences, not group differences. Preferably some dynamic measurements too (eg try to correlate between self reported stress over a few months and the other measurements).

    One good study is more useful than all these partial studies that only give us a small hint of the actual workings.
     
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  17. Waverunner

    Waverunner Senior Member

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    The study you proposed is urgently needed. It seems to me however that the problem of simplification is present in most parts of medicine. For example if we look at intestinal permeability or the BBB we see that both have gigantic importance for human health but neither diagnostics nor treatments are available. The standard haemogram hasn't change much from the haemogram 30 years ago. This is really shameful if you take into account how much progress we had in the field of electronics. Why is this? Why do we seem to have so little progress in the field of medicine? We have so many little breakthroughs and interesting, mind opening studies but these studies don't get transformed into diagnostics or treatments. Why?
     
  18. Glynis Steele

    Glynis Steele Senior Member

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    Here is an interesting mouse study regarding stress, bacterial translocation and increased cytokines.

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039072/?tool=pubmed

    Here is what a psychiatrist makes of this study on her blog, quite refreshing considering!:

    http://evolutionarypsychiatry.blogspot.co.uk/2011/03/stress-and-your-gut-or-at-least-mouses.html
     
  19. Firestormm

    Firestormm Guest

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    Yep. Personally I would also like to know what effect this (type?) of inflammation has on a person's ability to function. What does it do precisely? I mean here we are talking about cell inflammation I think - so how does that equate with, say, neuro-inflammation or brain inflammation more precisely? And can this sort of inflammation be detected by, say, SPECT scans or are we again talking about something totally different?

    Take viral encephalitis or encephalomyelitis if you like - as I said above - are these the same/similar/different 'types' of inflammation and how are they detectable/quantifiable? As you say, the 'field' has a long way to go before e.g. psychiatrists can claim X-inflammatory response causes e.g. depression or is a side-effect of depression - or as in an example in the above - loneliness...
     
  20. Marco

    Marco Old blackguard

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    I've no problem with considering the possibility that chronic stress might lead to 'CFS' in some cases. Psychological and other stressors certainly exacerbate the symptoms.

    Not only does stress cause inflammation and disease but epigenetic changes may allow it to be passed from generation to generation and may have played an important evolutionary role in the distant past (excuse the source here - the information is genuine) :

    http://www.reuniting.info/node/5139

    Hypervigilance to symptoms is what the BPS squad have long accused us of but hypervigilance may be 'hard wired' in to certain individuals.

    Here's the possible mechanism for those interested :

    http://www.sciencedaily.com/releases/2011/06/110623130146.htm


    Even without an inherited predisposition, animal models can show how early infection can 'prime' an individual to be susceptible to later life stress. The double hit theory of infection and stress :

    http://www.sciencedirect.com/science/article/pii/S0306453009001607

    Depression has long been associated with coronary heart disease and depression and anxiety are common symptoms of prolonged infection and immune activation. Inflammation is known to be a precursor to heart disease. Sorting out the chicken from the egg is no easy task.
     

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