24 October 2012 Last updated at 00:48 GMT
Placebo effect may be 'down to genes'
Why some people respond to treatments that have no active ingredients in them may be down to their genes, a study in the journal PLoS ONE suggests.
The so-called "placebo effect" was examined in 104 patients with irritable bowel syndrome (IBS) in the US.
Those with a particular version of the COMT gene saw an improvement in their health after placebo acupuncture.
The scientists warn that while they hope their findings will be seen in other conditions, more work is needed.
Edzard Ernst, a professor of complementary medicine at the University of Exeter, said: "This is a fascinating but very preliminary result.
"It could solve the age-old question of why some individuals respond to placebo, while others do not.
"And if so, it could impact importantly on clinical practice.
"But we should be cautious - the study was small, we need independent replications, and we need to know whether the phenomenon applies just to IBS or to all diseases."
The placebo effect is when a patient experiences an improvement in their condition while undergoing an inert treatment such as taking a sugar pill or, in this case, placebo acupuncture, where the patient believes they are receiving acupuncture but a sham device prevents the needles going into their body.
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While this is a very interesting work, what we have learned in the past few years is that there is not a single placebo response and a single mechanism”
Prof Fabrizio Benedetti
University of Turin Medical School
Two groups in the study had this type of treatment. One group received it in a business-like clinical manner and the other from a warm supportive practitioner. A third randomly chosen group received no treatment at all.
After three weeks the patients were asked if they had seen an improvement in their IBS, a common gastrointestinal disease that can cause abdominal pain and discomfort.
The team then used blood samples to look at what variant the individual had of the catechol-O-methyltranferase (COMT) gene. This plays a role in the dopamine pathway, a chemical known to produce a feel-good state.
Paper author Dr Kathryn Hall, from the Beth Israel Deaconess Medical Center (BIDMC), said this gene had been chosen because "there has been increasing evidence that the neurotransmitter dopamine is activated when people anticipate and respond to placebos".
The researchers found individuals with a COMT variant that triples the amount of dopamine in the front of the brain felt no improvement without treatment but an improvement with the placebo acupuncture.
Ted Kaptchuk, director of the Program in Placebo Studies and Therapeutic Encounter at BIDMC, said: "We wanted to tease apart the different doses of placebo.
"We got an effect in individuals with this specific genetic signature for the general placebo, but an even bigger effect in the elaborate placebo where warmer care was given.
"You can really see the advantage of a positive doctor-patient relationship."
Fabrizio Benedetti, professor of neurophysiology at the University of Turin Medical School, Italy, warned that dopamine may not be the only chemical involved with the placebo effect.
"A previous study on the genetics of placebo in social anxiety disorder showed that it is serotonin that is associated to placebo responsiveness and not dopamine," he said.
"While this is a very interesting work, what we have learned in the past few years is that there is not a single placebo response and a single mechanism, but many, across different medical conditions and therapeutic interventions."
PLoS One. 2011 Mar 18;6(3):e18035.
The relationship between the val158met catechol-O-methyltransferase (COMT) polymorphism and irritable bowel syndrome.
Karling P, Danielsson Å, Wikgren M, Söderström I, Del-Favero J, Adolfsson R, Norrback KF.
Division of Medicine, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden. firstname.lastname@example.org
The catechol-O-methyltransferase (COMT) enzyme has a key function in the degradation of catecholamines and a functional polymorphism is val158met. The val/val genotype results in a three to fourfold higher enzymatic activity compared with the met/met genotype, with the val/met genotype exhibiting intermediate activity. Since pain syndromes as well as anxiety and depression are associated to low and high COMT activity respectively and these conditions are all associated with irritable bowel syndrome (IBS) we wanted for the first time to explore the relationship between the polymorphism and IBS.
867 subjects (445 women) representative of the general population and 70 consecutively sampled patients with IBS (61 women) were genotyped for the val158met polymorphism and the IBS patients filled out the Hospital-Anxiety-and-Depression-Scale (HADS) questionnaire, and an IBS symptom diary.
There was a significantly higher occurrence of the val/val genotype in patients compared with controls (30% vs 20%; Chi(2) (1) 3.98; p = 0.046) and a trend toward a lower occurrence of the val/met genotype in IBS patients compared with controls (39% vs 49%; Chi(2) (1) 2.89; p = 0.089). Within the IBS patients the val/val carriers exhibited significantly increased bowel frequency (2.6 vs 1.8 stools per day; Chi(2) (1) 5.3; p = 0.03) and a smaller proportion of stools with incomplete defecation (41% vs 68%; Chi(2) (1) 4.3; p = 0.04) compared with the rest (val/met+met/met carriers). The val/val carriers also showed a trend for a smaller proportion of hard stools (0% vs 15%; Chi(2) (1) 3.2; p = 0.08) and a higher frequency of postprandial defecation (26% vs 21%; Chi(2) (1) 3.0; p = 0.08).
In this study we found an association between the val/val genotype of the val158met COMT gene and IBS as well as to specific IBS related bowel pattern in IBS patients.
PMID: 21437260 [PubMed - indexed for MEDLINE] PMCID: PMC3060919
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