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CBT non-responders and low cortisol

Discussion in 'Latest ME/CFS Research' started by kaffiend, Sep 8, 2011.

  1. kaffiend

    kaffiend Senior Member

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    This article is a couple of years old, but I didn't see it discussed anywhere. The abstract is pasted below.

    Of 82 patients, 39% were responders to cognitive behavioral therapy (as measured with Clinical Global Impression scale) and 61% were non-responders. It's interesting because the authors identify a biomarker (low morning cortisol) for non-responders. This doesn't get the attention it deserves. By the way, I just started low-dose hydrocortisone last week and feel almost cured of any post-exertional symptoms so far.

    Cortisol for CBT responders & non-responders
    Screen Shot 2011-09-08 at 1.58.04 PM.jpg



    Does hypocortisolism predict a poor response to cognitive behavioural therapy in
    chronic fatigue syndrome?

    A. D. L. Roberts1,2, M.-L. Charler2, A. Papadopoulos3, S. Wessely1,2,3, T. Chalder1,2 and A. J. Cleare1,2,3*
    1 Kings College London, Institute of Psychiatry, Department of Psychological Medicine, London, UK 2 Chronic Fatigue Syndrome Research and Treatment Unit, Maudsley Hospital, London, UK
    3 National Affective Disorders Unit, Maudsley and Bethlem Royal Hospitals, London, UK

    Background. There is evidence that patients with chronic fatigue syndrome (CFS) have mild hypocortisolism. The clinical significance of this is unclear. We aimed to determine whether hypocortisolism exerted any effect on the response of CFS to cognitive behavioural therapy (CBT).

    Method. We measured 24-h urinary free cortisol (UFC) in 84 patients with Centers for Disease Control and Prevention (CDC)-defined CFS (of whom 64 were free from psychotropic medication) who then received CBT in a specialist, tertiary out-patient clinic as part of their usual clinical care. We also measured salivary cortisol output from 0800 to 2000 h in a subsample of 56 psychotropic medication-free patients.

    Results. Overall, 39% of patients responded to CBT after 6 months of treatment. Lower 24-h UFC output was associated with a poorer response to CBT but only in psychotropic medication-free patients. A flattened diurnal profile of salivary cortisol was also associated with a poor response to CBT.

    Conclusions. Low cortisol is of clinical relevance in CFS, as it is associated with a poorer response to CBT. Hypocortisolism could be one of several maintaining factors that interact in the persistence of CFS.
  2. ukxmrv

    ukxmrv Senior Member

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    I remember the paper from that time. I was discussed at the time on the net. Maybe one of the reasons it's not been hyped is that it was old news and because SW was one of the authors.

    Give the hydrocortisone a bit longer and see how it works out for you. There was a lot of excitment about HC in the early 90's and lots of patients took it then. Some found a short term benefit, some didn't, some are still taking it from then.

    I've got low AM cortisol BTW so always on the lookout for info. There's a few threads on this forum about treating low cortisol.
  3. kaffiend

    kaffiend Senior Member

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    I don't think HC would have worked for me until recently. I had to identify a lot of precipitating factors that went nuts after the onset of my illness (food sensitivities and reactive hypoglycemia) before I began to feel better.
  4. Esther12

    Esther12 Senior Member

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    I think I had this tested at some point. No idea what my result was. Thanks for mentioning the paper.
  5. kaffiend

    kaffiend Senior Member

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    My cortisol levels are within normative ranges in serum. I don't know if static or baseline measures will reveal the true dysfunction in ME. The figure below demonstrates this point (taken from The crucial role of pulsatile activity of the HPA axis for continuous dynamic equilibration, Nature Reviews Neuroscience, Oct 2010).

    Overall, cortisol levels are higher in the morning and fall throughout the day, but they also oscillate within the circadian (daily) rhythm. The averaging across people done in most studies smooths out this curve and the within daily (ultradian) oscillation is lost. An exercise/stress or ACTH challenge would be needed. Or a repeated (day 1; day 2) exercise/stress challenge directed at determining the responsiveness of the system.

    Screen Shot 2011-09-08 at 4.05.16 PM.jpg
  6. In Vitro Infidelium

    In Vitro Infidelium Guest

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    This research is following the 'stress hypothesis' that proposes M.E/CFS is a chronic response to a previous trauma, and is (although neurochemically identifiable) ultimately a behavioural issue. As CBT isn't 'working' in a group of patients and the hypothesis demands that it should, the researchers are following a further unspoken hypothesis that states there must be something excpetionally 'wrong' in the CBT non responders. The direction of the research is prefigured by the 2006 precursor to this 2009 study Childhood Trauma and Risk for Chronic Fatigue Syndrome - the low cortisol/trauma relationship has been developed over the last two decades - Neurobiological Stress Responses to Child Abuse and Neglect . For a relevant (if inexpert) discussion on some of the issues - User talk:In Vitro Infidelium .

    Cortisol may indeed play a role in M.E/CFS symptomolgy, but the implications may not be what everyone expects. The research can't be rejected just because it is 'interpretable' in psychiatric terms, but we should all be aware of the direction that the research is going.

    IVI
  7. Enid

    Enid Senior Member

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    That's an interesting one kaffiend - it ties in with a period of my own adrenal problems. High levels of potassium were found (excreted) in my urine and usually taken as adrenal insufficiency (presumably affecting cortisol production too). Definately not the sort of problem to take to a psychiatrist, CBTist or GETist.One feels pretty ill too.
  8. kaffiend

    kaffiend Senior Member

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    I don't agree with the discussion contained in most research papers. They are, in many cases, throw-away sections for the authors to justify what went wrong with the hypothesis. In this case, that patients with low cortisol probably need even more CBT. Despite the spin, the results are interesting: a majority (close to 2/3) of the studied ME/CFS patients didn't respond to CBT and a biomarker can be identified in this majority.

    I'm taking HC (and supplements and elimination diet and...) and don't agree that CBT and/or GET can be considered as principle treatment strategies. The available evidence for them is also quite weak. I am however at a point where my own versions of CBT and GET are part of recovering. I progressively take on more physical and intellectual activity, paying attention to the consequences and symptoms. This is at variance with the published rationale of CBT and GET which indicate that ignoring one's symptoms will lead to their improvement. I've still felt like dogshit at several times, but it hasn't been debilitating, and so I can push through it. That would have been devastating and dangerous for me just a few weeks and months ago.
  9. Dolphin

    Dolphin Senior Member

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    The 2006 and 2009 studies used the so-called empiric criteria for CFS (Reeves et al., 2005). These cover 2.54% of the population. I think they are rubbish criteria for ME/CFS or CFS and so think they tell us little about the condition. I find it a pity that potentially useful research i.e. the CDC program in general, has been spoiled by such rubbish criteria. I even complain about these criteria in my signature i.e. this isn't a short term position of mine.
    WillowJ likes this.
  10. Sean

    Sean Senior Member

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    The stress-o-genic model of ME/CFS requires that objective measures of significantly increased stress be found in patients prior to onset.

    Far as I know the objective biochemical evidence so far shows that the stress system is behaving normally before, during, and in the first few months immediately following onset.

    This result supports the interpretation that any stress related symptoms in these patients are more likely to be the generic long-term secondary consequences of having the disorder, rather than a specific immediate primary cause of it.

    Which is not to say that these secondary consequences are not clinically significant, or should be ignored, but they are not the main issue.
  11. In Vitro Infidelium

    In Vitro Infidelium Guest

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    Heim et al 2009 actually serves to raise questions about the patient population selection, although the authors choose to think mono directionally and see the results as confirmation of hypothesis and not an indication of possible confounding effects. Any study which selects on reported physiological symptomology, and which goes on to produce data indicating 33% prevalence of multiple facet child abuse among the study population should raise alarm bells for the researchers. Why is that this very particular form of childhood trauma produces physiological effect and not illness or accident in childhood ?

    What of course Heim et al doesn't tell us is how prevalent M.E/CFS is amongst the whole population of those reporting childhood abuse, if that data were available then the M.E/CFS criteria used would certainly be critical. Were there to be a high correlation between childhood abuse and adult M.E/CFS evident across criteria sets (Fukada etc), then a chronic effect of childhood abuse could be hypothesised as a contributory factor in M.E/CFS causation in a subset of M.E/CFS sufferers, with implications for the nature of the disease process in the wider (non abuse) M.E/CFS sufferer population.


    It's very unlikely that any pre illness data exists, which leaves the stress hypothesis untestable - indeed unfaslsifiable and therefore unless substantially reconfigured, probably not scientifically valid. Life event data is interesting but it is very difficult to get past 'correlation is not causation', even where the correlation is statistically very strong, it is one of the major limitations of the biopsychosocial model because its application to research often requires chronological data which is uncollectable.

    IVI
  12. Sean

    Sean Senior Member

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    Cleare argues the evidence shows there is no stress activation at onset or shortly thereafter. (This paper is 7 years old, but pretty sure the evidence published since then supports his position.)

    Cleare AJ, Trends Endocrinol Metab. 2004 Mar;15(2):55-9.
    The HPA axis and the genesis of chronic fatigue syndrome.

    http://www.ncbi.nlm.nih.gov/pubmed/15036250

    There is some discussion of that paper and its implications here, and here (scroll down a bit, starts after the line 'A trigger is a short-time event.').
  13. kaffiend

    kaffiend Senior Member

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    I recently learned that T lymphocytes themselves secrete corticotropin releasing hormone (CRH). CRH is normally released from hypothalamic neurons to (indirectly) increase cortisol release from the adrenals. Chronically activated T lymphocytes would perturb the normal cortisol response and cycle.

    Such activation could provide a mechanism for sleep reversal and HPA-dysfunction. Under "normal" circumstances, T cell proliferation would provide a negative feedback on itself.

    Relevant paper here
  14. bertiedog

    bertiedog Senior Member

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    I have to take Prednisolone and a bit of h/c everyday and half a tab of Florinef but in my case I think the deterioration of my adrenals was progressive. I was given h/c in 2002 when the private doctor I saw felt that the very high DHEA on my 24 hour cortisol/DHEA saliva tests but lowish cortisol at midday showed that my body was asking for more cortisol but the adrenals were unable to respond and instead over produced DHEA. He felt it fitted with my symptoms of panic attacks and exhaustion. There is a Pubmed study which shows a good response in fatigue in people with CFS who have high DHEA and low cortisol.

    At the time it was also found I had Hashimotos thyroid disease and was treated with Armour. There was a definite improvement but in no way was I ever able to walk more than 20 minutes without energy running out. However the next day I am usually recovered unless I have a virus or infection.

    I managed to gradually come off the steroids in 2005 for a short time but developed 2 adrenal crises over 2 months which were very frightening (non stop vomiting and diahorea which led to my passing out and being unable to get off the floor until I was given some h/c). After that I knew I would be on steroids for the rest of my life barring a miracle.

    There have been improvements especially in my mental outlook. The panic attacks are gone and I usually feel quite optimistic and feel quite laid back about life. However I still get frequent infections which make me feel very bad and recently a blood test showed I had a high level of herpes-type infections in my blood.

    On a final point I did suffer from a form of child abuse as I had a father who was very domineering and threatening and would on occasions hit me if I didnt do what he wanted and I am sure this wasnt a positive experience for my health.

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