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The buspirone challenge test clearly distinguishes ME/CFS patients from healthy controls: why is it not being developed and deployed?

Discussion in 'MEpedia' started by Hip, Oct 30, 2018.

  1. Hip

    Hip Senior Member (Voting Rights)

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    Arguably the best ME/CFS blood test we have at present is the one used by Myhill et al in their studies on mitochondrial energy metabolism (namely the "ATP Profiles" test from Acumen Lab). That not only correctly categorized almost every patient and healthy control under the right label (their studies looked at around 200 patients), but also, the measured degree of energy metabolism blockage in the "ATP Profiles" test correlated quite well with the severity of ME/CFS (as measured on the Bell scale).

    Unfortunately that test and those studies have not been independently replicated (but an independent replication study is being conducted). And also it's only this one small specialist lab in the UK which provides the test.

    I know one case of an ME/CFS patient whose family thought her illness was "all in the mind", but once she had this test at Acumen Lab which showed poorly functioning mitochondria, the family finally understood that it was a real illness.



    Interesting, I did not notice that.

    (Neurasthenia is the name of an illness similar to ME/CFS that was routinely diagnosed from around 1870 to 1950. In the early period of its life, neurasthenia was considered a neurological disease, and treated by neurologists. But later on, it appears that the psychologists/psychiatrists may have moved in, taking over control of the disease (now where have I come across that before)? Although most of the details of this are lost in history. A history of neurasthenia is provided in this paper.)

    But anyway, the two earlier papers on the buspirone challenge test were by Prof Peter Behan and Dr John Richardson, both from the classic ME camp.
     
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  2. Alvin

    Alvin Senior Member (Voting Rights)

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    Again i don't argue against we could do with a good diagnostic test, but we really need a good, proofed diagnostic test.
     
    Last edited: Nov 1, 2018
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  3. alex3619

    alex3619 Senior Member (Voting Rights)

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    We have had so many candidate tests, but none have received the research need to go to the next step. The group currently doing the most here is OMF which has 5+ tests about to be compared to each other. Four more are in development at various labs. Next year might be interesting.
     
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  4. Alvin

    Alvin Senior Member (Voting Rights)

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    Indeed, i hope one or more become verified and most importantly don't turn out to not be diagnostic. This second part is the hardest, things work much better in a lab then in the real world and if something is later shown to be associated with another disease as well it can be a huge PR blow but its a risk thats very hard to mitigate without lots of money, researchers and time, all things we don't have.
    The one thing i would really love to see is the molecule causing the signal in the nanoneedle to be identified, if it leads to a core part of the ME mechanism then it helps guard against problem i just mentioned.
     
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  5. Inara

    Inara Senior Member (Voting Rights)

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    claimed to be similar :) others compare it with Burnout. Whatever you choose...
     
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  6. alex3619

    alex3619 Senior Member (Voting Rights)

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    (neurasthenia)
    My understanding is that originally neurasthenia was basically male hysteria, since males obviously could not be hysteric. Later its meaning changed and female patients started being diagnosed. While some diagnoses were made in the twentieth century, I recall one hospital finding that most diagnoses of neurasthenia ceased (at least in the UK) very early in the century. I am not familiar with modern usage, though every now and again many old diagnoses resurface. I investigated this years ago, and I think used papers by Beard from the nineteenth century.
     
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  7. Inara

    Inara Senior Member (Voting Rights)

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    What you say is correct as far as I know:
    Beard described a symptom complex and called it Neurasthenia. First, he viewed that as neurological. I don't know the specifics, but in the coming years it was claimed to be psychiatric. At the beginning its reputation was good, and it was mainly used for men, in contrast to hysteria. In the First World War, many soldiers returned sick, and for many an "organic" reason couldn't be found. In order not to dishonor them, they were diagnosed with Neurasthenia (instead of hysteria). That changed in World War II. btw. Even Baur-Fischer-Lenz (1921) write positive about Neurasthenia, and there seems to have been a hype around 1914. Later it developed to be a second hysteria, including bad reputation, and then it fanned out.

    What I meant with my statement: I don't see how we can say today what Neurasthenia really was. Today, some people equal it with Burnout, and as we know, some with ME, CF, CFS. Chances are high that it was a "diagnosis" for people whose symptoms were unknown (like closed head injuries). For me it feels ridiculous and scandalous to adopt a 19th century diagnosis and say - without allowing a doubt - that Neurasthenia is exactly the same as...you name it...without any proof, only that the symptoms Beard described remind some people of....you name it...

    For a diagnosis of Burnout, a Z code should be used, but many use F48.0 instead, amongst others. So today, what we can say is, indeed, we have a comparable situation to around 1914, whatever you can't explain and has anything to do with tiredness or exhaustion you put into F48.0. They would use hysteria for women if they could, but there's no code. They don't even try to understand what these symptoms are (research!).
     
  8. Hip

    Hip Senior Member (Voting Rights)

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    That may well be right, diagnostic accuracy may not have been that great 150 years ago when neurasthenia first came on the scene, and a range of conditions might have been included under that diagnostic label.

    Though the Sharpe paper says patients met the World Health Organization 1992 criteria for neurasthenia, so I presume they must have matched the WHO symptom list.

    The WHO criteria for neurasthenia given here (note that there are two main subtypes of neurasthenia):
    F48.0 Neurasthenia

    Considerable cultural variations occur in the presentation of this disorder; two main types occur, with substantial overlap.

    In one type, the main feature is a complaint of increased fatigue after mental effort, often associated with some decrease in occupational performance or coping efficiency in daily tasks. The mental fatiguability is typically described as an unpleasant intrusion of distracting associations or recollections, difficulty in concentrating, and generally inefficient thinking.

    In the other type, the emphasis is on feelings of bodily or physical weakness and exhaustion after only minimal effort, accompanied by a feeling of muscular aches and pains and inability to relax.

    In both types, a variety of other unpleasant physical feelings, such as dizziness, tension headaches, and a sense of general instability, is common. Worry about decreasing mental and bodily well-being, irritability, anhedonia, and varying minor degrees of both depression and anxiety are all common. Sleep is often disturbed in its initial and middle phases but hypersomnia may also be prominent.

    Diagnostic guidelines

    Definite diagnosis requires the following:

    (a) either persistent and distressing complaints of increased fatigue after mental effort, or persistent and distressing complaints of bodily weakness and exhaustion after minimal effort;

    (b) at least two of the following:
    - feelings of muscular aches and pains - dizziness
    - tension headaches
    - sleep disturbance
    - inability to relax - irritability
    - dyspepsia;

    (c) any autonomic or depressive symptoms present are not sufficiently persistent and severe to fulfill the criteria for any of the more specific disorders in this classification.

    Includes: fatigue syndrome

    Differential diagnosis. In many countries neurasthenia is not generally used as a diagnostic category. Many of the cases so diagnosed in the past would meet the current criteria for depressive disorder or anxiety disorder. There are, however, cases that fit the description of neurasthenia better than that of any other neurotic syndrome, and such cases seem to be more frequent in some cultures than in others. If the diagnostic category of neurasthenia is used, an attempt should be made first to rule out a depressive illness or an anxiety disorder. Hallmarks of the syndrome are the patient's emphasis on fatiguability and weakness and concern about lowered mental and physical efficiency (in contrast to the somatoform disorders, where bodily complaints and preoccupation with physical disease dominate the picture). If the neurasthenic syndrome develops in the aftermath of a physical illness (particularly influenza, viral hepatitis, or infectious mononucleosis), the diagnosis of the latter should also be recorded.

    Excludes:
    asthenia NOS (R53)
    burn-out (Z73.0)
    malaise and fatigue (R53)
    postviral fatigue syndrome (G93.3)
    psychasthenia (F48.8)


    Source: The ICD-10 Classification of Mental and Behavioural Disorders
     
    Last edited: Nov 2, 2018
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  9. Inara

    Inara Senior Member (Voting Rights)

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    Haha, they even have psychasthenia, I can't believe it! Baur-Fischer-Lenz (a well-known book about eugenics from 1921) had the opinion, Neurasthenia would be better described by psychasthenia (p. 552). But "neurasthenia is more gentle, more polite, therefore it is more used."

    (I'm sorry for going off-topic @Hip.)
     
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  10. alex3619

    alex3619 Senior Member (Voting Rights)

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    Diagnostic accuracy is not great for nearly all of psychiatry even now. There are no tests. Its all supposition according to guidelines. Its not that things are not wrong with patients, its that we think the labels give us an understanding of what is going wrong. I suspect the false diagnosis rate is close to 100%. Labels are not scientific answers. When tests are developed the diagnosis is often moved to neurology.

    I suspect that some of the physiological abnormalities in, for example, depression, are probably diagnostic for subgroups, but its hard to prove. Depression is a symptom range that is very common, like pain or fatigue, and should probably not even be a diagnosis at all, just a symptom of many diagnoses. Many psychiatric disorders are just made up, because a bunch of psychiatrists at a DSM meeting thought it was a good idea. Now this is a very difficult area of medicine, the brain is still almost a black box, but the appropriate cautions this should lead to are often ignored in favour of ill-informed diagnosis.

    I do not know enough about WHO ICD diagnostic development processes to discuss how they compare to DSM.
     
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  11. Alvin

    Alvin Senior Member (Voting Rights)

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    This is why they create the DSM, they group symptoms together that they think are separate diseases, call it X, Y, Z and voila you have "science"

    Human nature does not change every 5 years or so yet "diseases" come and go and are redefined.

    Emotional trauma is emotional trauma, making up (artificial) distinctions is rather intuitive but in the grand scheme means little

    In the end the DSM is a political document and these diagnoses are a "good faith" attempt to quantify what they don't understand and look at incorrectly.
     
    Last edited: Nov 2, 2018
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  12. Manganus

    Manganus Established Member (Voting Rights)

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    I do agree on your estimation (close to 100%), but not on what you then write. ;)

    People who appear insane to their peers do really exist.
    And one way or another, they (or we) are to be cared for. Psychiatry is far from perfect, but still irreplaceable until better knowledge is achieved. Depression is not the same as feeling sad or missing someone one has lost. Maniacs do really exist, in the meaning people suffering from mania. The condition causes immense troubles for friends, family and themselves. Schizophrenics do also exist. Really!
     
    Last edited: Nov 2, 2018
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  13. Hip

    Hip Senior Member (Voting Rights)

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    Sure the mental health labels do not explain how the mental health symptoms arise; but diagnosis and label-giving are vital to ensure patients get the right treatment. The right label may not necessarily be arrived at on the first diagnosis; but that's true of physical diseases of the body as well.

    It will probably take at least another 100 years before we fully understand the neurological or immunological mechanisms behind the various mental health disorders; but even without really understanding the mechanisms, there are pretty good pharmacological treatments available today for many psychiatric conditions. So in this field, the science of treatment is more advanced than the understanding of the causal brain mechanisms.

    Mental ill-health can involve enormous suffering, so accurate diagnosis, labelling and pharmacological treatment is very important, in order to try to mitigate this human suffering.
     
    Last edited: Nov 2, 2018
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  14. alex3619

    alex3619 Senior Member (Voting Rights)

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    Of course. These people can also be suffering greatly, and it can even be life threatening. This does not mean we understand what we see. There is very little quality science either. Not zero, its just its in the minority.


    Except this is the exception, not the rule. There is a subgroup in depression, for example, who respond fantastically to antidepressants. Then there is the rest. In those some might have a minor response, and a big chunk is placebo at best. I would love to see the cause identified, and a real cure. Like the doctor who cures about 80% of depressed teenagers using antivirals. Or patients with metal poisoning or nutritional deficiencies getting chelation or dietary advice and supplemental vitamins. Find the cause, cure it.

    There is no question that many talk therapies can supply counselling to help people cope even though we do not understand or have cures. Yet without understanding of the deep biology there is typically no cure. How many patients are actually cured? Any? I think many of the claimed cures are because these problems go away on their own. I do think that patients cope better with various psychotherapies, but real treatment should be aimed at cure.

    If a diagnostic category is flawed and the patient cohort highly heterogeneous, and its not focused on subgroups, then treatments are likely to be mis-targeted. If the category does not even match a real disease, then treatments are entirely experimental.

    Psychiatry is no different from other medicine, it needs diagnostic biomarkers. Arguments against this suffer from many flaws, but I do not want to get into that here.

    Which is why I like research into tests like the one discussed here.
     
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  15. Hip

    Hip Senior Member (Voting Rights)

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    Oh indeed! We do need to get the the root cause of the numerous mental health illnesses that humanity is afflicted with; modulating neurotransmitters with drugs is more of a band-aid approach.
     
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