Genetic underpinning of placebo effect identified

Nov 1 2012

By medwireNews Reporters

US researchers have identified a gene that appears to be responsible for the placebo effect.

Specifically, they showed that the catechol-O-methyltransferase (COMT) val158met functional polymorphism is an important predictor for response to placebo.

COMT is an enzyme involved in dopamine catabolism and plays a major role in processes such as reward, pain, memory, and learning.

"There has been increasing evidence that the neurotransmitter dopamine is activated when people anticipate and respond to placebos," lead investigator Kathryn Hall (Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA) said in an accompanying press statement. "With this new research, we may now be able to use a person's genetic makeup to predict whether or not they will respond to a placebo."

Published in PLoS One, the study included 104 irritable bowel syndrome (IBS) patients who had participated in a previously reported randomized controlled trial.

Patients in the study were assigned to one of three treatment arms: no treatment and placed on a waiting list, placebo treatment alone, or placebo therapy augmented with a supportive healthcare provider.

The researchers measured changes in the IBS-Symptom Severity Score (IBS-SSS) from baseline to after 3 weeks of "treatment."

In a regression model, the number of methionine alleles in COMT val158met was significantly and linearly associated with the placebo response as measured by changes in the IBS-SSS.

Individuals who were homozygous for met/met and treated in the augmented placebo arm had the largest improvement in IBS symptoms.

"Our regression analysis found that as the copies of met increased, placebo responses increased in a linear fashion, presumably because more dopamine was available," Hall remarked.

A smaller change in IBS-SSS was observed in met/met homozygotes treated with placebo alone and there was no reported change in symptoms in the waitlist patients.

Compared with individuals without any methionine alleles, the val/val patients, homozygous met/met individuals had a sixfold improvement in their IBS symptoms.

Previous studies have shown that individuals with the met/met polymorphism have increased sensitivity to experimental and chronic pain compared with those with the val/met and val/val polymorphisms.

"These findings suggest that it is possible that met/met is a genetic marker for the placebo response and val/val is a marker for non-response," according to Hall.

The findings, say the researchers, could have large implications for designing clinical trials. If it is possible to predict and control the placebo response, it could have a major impact in terms of reducing the size, cost, and duration of clinical trials, they explain.

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