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Placebo Effect may be Genetic

Discussion in 'Other Health News and Research' started by Hip, Dec 10, 2012.

  1. Hip

    Hip Senior Member

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    The placebo effect was examined in 104 patients with irritable bowel syndrome (IBS). Those with a particular version of the COMT gene saw the greatest improvements in their health after placebo acupuncture.

    Source: BBC News - Placebo effect may be 'down to genes'

    The catechol-O-methyltransferase (COMT) gene, which determines levels of dopamine in the brain's prefrontal cortex, is linked to differences in reward-seeking and pain perception. People with the high-dopamine version of this COMT gene feel pain more acutely and seek rewards more strongly than those who have the low-dopamine version.

    People with the high-dopamine allele of the gene may do well on the placebo with the nurturing treatment because they are generally more attuned to their environments.

    Source: Placebo Effect May Be In the Genes | LiveScience

    One or more met alleles in the COMT gene acts to increase levels of dopamine in the prefrontal cortex. This study found that the more met alleles you have, the more you respond to the placebo effect:
    • Patients who had two copies of the met allele (met/met) in their COMT gene showed the greatest improvements in their IBS symptoms.
    • Patients with one copy of the met allele (val/met), had an intermediate response.
    • Patients carrying no copies of the met allele, and two copies of the val allele (val/val), showed the least improvements in their IBS symptoms.

    Source: Placebo Effect Linked to Dopamine-Clearing Enzyme

    Published paper:
    Catechol-O-Methyltransferase val158met Polymorphism Predicts Placebo Effect in Irritable Bowel Syndrome
  2. Valentijn

    Valentijn Activity Level: 3

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    Nice to see some real science looking at a typically psychologically-attributed phenomenon.

    It might also help in differentiating between subjectively feeling less pain (due to dopamine) and objective improvement in the medical condition.
    Waverunner likes this.
  3. Hip

    Hip Senior Member

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    What I read in one of the writeups is this:

    If the placebo effect only occurs in individuals with a specific genetic makeup, and does not occur in other people, using this knowledge could save billions in the costs of performing scientific and clinical trials of drugs and treatments, because at present you always have to include a control group of individuals who are given a placebo treatment, as well as the treatment group, who are given the actual new drug or treatment being tested.

    If you could entirely eliminate the placebo effect in your trial, by only including in your trial individuals who were not genetically susceptible to the placebo effect, you could roughly halve the number of people involved in your testing, and thus reduce the cost and complexity of running the trial.
  4. Hip

    Hip Senior Member

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    I also wonder whether the results of this study on the placebo effect might have some bearing in the highly controversial area of psychogenic factors influencing ME/CFS.

    Sure, we all agree that ME/CFS is a physical disease, likely driven by chronic microbial infection and other physical causes; but for individuals that possess the met/met allele, who will experience the largest increase in dopamine in their prefrontal cortex when given nurturing treatment, this dopamine boost may well affect their ME/CFS symptoms.

    So people with ME/CFS that claim they benefitted from some psychological treatment, like for example Mickel Therapy (which is essentially purely a talk therapy), might conceivably have the met/met allele, which means that their brain's prefrontal cortex will be infused with dopamine when they are nurtured in a warm fashion, and it is this dopamine boost that could be responsible for physically improving their ME/CFS symptoms.

    Perhaps this dopamine boost might improve the immune response, or reduce autoimmunity? Or maybe the dopamine boost just makes you feel better, so that your ME/CFS is the same, but you report improvements.

    Pure speculation, yes, but this might throw some light on how and why some people with ME/CFS say they improve with psychological interventions, and why others say they don't. The reason may be genetic.
    Little Bluestem and Marco like this.
  5. penny

    penny Senior Member

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    I feel like I've read some, probably casual, references in the past to ME sufferers being less susceptible to placebo. Am I making this up or is it something (rumor, observation, study results)?

    I consider myself very resistant to placebo (though you'll have to take my word for it ;) but just looked up my snp on 23 and me and I seem to be a combo met/val. I believe the snp they are referring to is this one: http://snpedia.com/index.php/Rs4680 (good old 'warrior' gene associated with all kinds of stuff from schizophrenia to endometriosis).
  6. Hip

    Hip Senior Member

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    That's quite amazing, Penny. I did not realize that the 23 and me test provided such detailed information.

    Regarding ME/CFS sufferers being less susceptible to placebo:

    The above placebo study indicates that the susceptibility to placebo increases as dopamine levels in the prefrontal cortex increase. Now ME/CFS patients have low overall levels of dopamine (ref: 1), so this may mean that their prefrontal cortex dopamine levels are low too, presumably leading to less susceptibility to the placebo effect.
  7. Hip

    Hip Senior Member

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    Hopes and expectations of ME/CFS patients: a placebo-like response?

    I find that something akin to the placebo effect from a drug/supplement arises even weeks before I take it. I have frequently noticed that if I am in a despondent or depressed mood, but then I read about some new drug that is showing benefit for ME/CFS, and I order it online, just the fact that I know I will soon be testing this new drug already dramatically begins to improve my mood and outlook. This placebo-like effect is a combination of my hopes and expectations for the benefits the new treatment might bring.

    Indeed, I have often thought that the reason people with ME/CFS are so very enthusiastic about testing new drugs or supplements relates just as much to the fact that they are getting considerable mood-boosting benefits from these hopes and expectations, as is does to any real benefits the drug may deliver. I know myself that I generally feel much better when there is a hopeful treatment possibility on the horizon. That is not to say that all drugs and supplements taken by ME/CFS are just placebos; some certainly do seem to work; it is just to say that, even if it turns out that a supplement does not really work for you, nevertheless, the hopes and expectations generated by trialling that supplement still aways offer a beneficial mood boost, irrespectively.

    I think people people with ME/CFS might be unusually receptive to these hopes and expectations, and to their therapeutic benefits. In fact, this receptiveness may say something about the nature of ME/CFS.

    By contrast, you will not find the mood of clinically depressed individuals soaring upwards just on the thought of a new treatment on the horizon; very much the opposite in fact: clinically depressed individuals generally tend to negate and discount any hopes offered to them (such negation is one of the symptoms of clinical depression). This difference almost amounts to a useful differential diagnoses between ME/CFS and clinical depression patients: the ME/CFS patients are usually highly receptive to hopes and expectations, whereas the same hopes and expectations have little or no effect on the clinically depressed.

    When the supplement or drug that I have pinned my hopes on and ordered online finally arrives, and I actually get down to testing it, the positive mood arising from my hopes and expectations is maintained, but of course I am specifically on the lookout for any improvements that the supplement or drug may bring.
    Marco likes this.
  8. adreno

    adreno 3% neanderthal

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    Hip

    What is your genotype on rs4680?
  9. Hip

    Hip Senior Member

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    I have not had any genetic testing done so far. Would the 23andme.com test provide this information about rs4680?
  10. adreno

    adreno 3% neanderthal

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    Yes.
  11. Hip

    Hip Senior Member

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    Ah, yes of course, rs4680 being the name of the SNP in the COMT gene that can have values of Met or Val.

    I just had another look at the www.23andme.com website, and it seems that the price is now $99. I am fairly sure I looked at their website only a few months ago, and the price then was $299.

    I am going to order a 23andme test, that's a great price.
    adreno likes this.
  12. Sea

    Sea Senior Member

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    That's interesting about the placebo response Hip.

    There's quite a few of us who have ordered the 23andme test recently since they've dropped their price. Now I just have to be patient as they take longer to process because of the overwhelming response to their price cut.
  13. penny

    penny Senior Member

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    Maybe I'm being nitpicky but this doesn't seem like a placebo effect. It seems that for something to have a placebo effect it should 1) be perceived to effect a primary symptom of the illness 2) actually need to be ingested/applied.

    So while yes, the idea of a new possibly useful med provides hope and thus perhaps a change in mood, ME is not a mood disorder so does increased "hope" or "optimism" really have anything to do with "perceived or actual improvement in a medical condition"? Personally I don't think so.

    I mean it's lovely when my mood is good, and having some grain of hope usually does improve my outlook a bit, but hope/good mood really doesn't effect my symptoms.

    Hope might be the mechanism by which the placebo effect 'works' but that doesn't mean hope itself is a placebo.

    Hopefully ;) this makes some sense!
  14. Hip

    Hip Senior Member

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    Yes I agree with you Penny that the mood boost I get due to the hopes and expectations I have of a medication I am soon to take is not really the placebo effect proper, but seems to be something akin to a placebo effect.

    Let's call this mood boost that I am talking about the "hope and expectation effect", to distinguish it from the placebo effect.

    It seems to me that I don't actually get any proper placebo effects from taking supplements, and that I am relatively immune to the placebo effect (but this statement assumes I am an accurate observer of what goes on in my own mind).

    It will certainly be very interesting to get the results of my 23andme DNA genotyping test (which I have just ordered), to see whether I have the Met alleles (which the study posits makes you more responsive to the placebo effect), or the Val alleles (which the study posits makes you more immune to the placebo effect).

    But even though I think I don't get influenced by the placebo effect, I think I am very influenced by this "hope and expectation effect" I described — an effect that makes me happier and banishes any despondent mood.

    My idea is that being responsive to the "hope and expectation effect" of medications is a particular characteristic feature of ME/CFS patients. I don't know of any other patient group that experiments with all sorts of treatments as much as ME/CFS patients do.

    As I mentioned, I think this propensity to experimentation with new medications may be unconsciously driven by a strong "hope and expectation effect" in operation in ME/CFS patients (as well as the logical desire to find medications that work).

    What do others think? Do others here think they are also very responsive to a "hope and expectation effect"?
  15. penny

    penny Senior Member

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    Hmmm, interesting, though I just assumed this effect you describe is related to the fact that our illness has no accepted/widely successful treatment, so in many scenarios it's experiment or give up. So I'd see a "propensity to experiment" as related to the relative hopelessness of traditional medical treatment (and perhaps the relapsing remitting aspect) rather than anything inherent to us as patients. Though it does seem possible that those who choose to experiment are more heavily represented in support groups/online forums - so a form of self selection.

    I have seen similar hope/propensity to experiment first hand with a handful of folks with other diagnosis (MS, cancer), though this was long before I had first hand experience, and I've had no real exposure to the patient groups for other illnesses.
  16. Hip

    Hip Senior Member

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    Certainly the lack of any currently widely successful treatment is the logical reason we experiment. And another similar rationale for our myriad medication experiments is that we know from discussion and experience that what works for one person with ME/CFS does not always work for the next, so personal exploration of numerous medications becomes a necessity, if you want to find something that woks for you.

    But in addition to these perfectly logical and rational reasons to experiment with myriad medications, is such experimentation also driven by the desire to maintain hope, which then keeps the mood and spirits raised?
  17. Marco

    Marco Old blackguard

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    I wonder what percentage of the general population carry one or both of the the low activity COMT met allele?

    Would it by any chance approximate the (if memory serves me well) 30% of PACE participants who they claimed had 'recovered' under the CBT or GET 'superplacebo' arms using subjective measures but which didn't appear to help on the one objective measure?;)
  18. adreno

    adreno 3% neanderthal

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    Actually, you can see the prevalences on SNPedia.
  19. Marco

    Marco Old blackguard

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    Thanks Adreno.

    So about 25% met/met for the European population?

    Close enough?
  20. adreno

    adreno 3% neanderthal

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    It's an interesting theory :)
    Marco likes this.

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