The Placebome: Where Genetics and the Placebo Effect Meet

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Newswise BOSTON Placebos have helped to ease symptoms of illness for centuries and have been a fundamental component of clinical research to test new drug therapies for more than 70 years. But why some people respond to placebos and others do not remains under debate.

With the advent of genomics, researchers are learning that placebo responses are modified by a persons genetics, a discovery that raises important new questions regarding the role of the placebo in patient care and in drug development: How many genetic biomarkers exist? Can the medical field harness the placebo response to enhance personalized medical treatment? What might be the impact of placebo-drug interactions? And what will this new information mean for randomized clinical trials, which depend on placebo controls to test the efficacy of new drug candidates? Should a no-treatment control be added to future trials?

Researchers from the Program in Placebo Studies (PiPS) at Beth Israel Deaconess Medical Center (BIDMC) and from the Department of Medicine at Brigham and Womens Hospital (BWH) explore these provocative issues in a review of evidence from placebo studies and randomized clinical trials. Published online today in Trends in Molecular Medicine, the article introduces the concept of the placebome,and identifies a network of genes that could significantly influence medicine and clinical trial design suggesting that placebos play a larger role in health care than previously recognized.

Genetic sequencing is revealing that the placebo response is, in fact, a complex phenotype with an unfolding physiology, says corresponding author Kathryn T. Hall, PhD, MPH, a PiPS Research Fellow in the Division of General Medicine and Primary Care at BIDMC and Harvard Medical School. The study of genomic effects on the placebo response what we call the placebome -- is in its infancy, but there is already ample evidence that genetic variations in the brains neurotransmitter pathways modify placebo effects. As a result, placebo responses are emerging as a legitimate series of biological reactions that must be rigorously characterized for efficient pharmaceutical development and optimal patient care.

The article focuses on several key concepts for future research and discussion regarding the role of the placebome in health care.

The Role of the Neurotransmitter in the Placebo Effect

The placebo effect occurs when patients show improvement from treatments that contain no active ingredients. Scientists initially used behavioral instruments, such as personality measures, to predict which patients would respond to placebos, but over the past decade, the development of sophisticated neuroimaging technologies illuminated the activation of the brains neurotransmitter pathways in response to placebos. Because they are the chemical messengers that either excite or inhibit nerve function in the brain, many neurotransmitters play key roles in reward and pain, explains Hall. We hypothesized that genetic variation in the genes that encode the proteins in these neurotransmitter pathways might also modify placebo responses.

In 2012, Hall identified the first placebo biomarker, the catechol-O-methyltransferase (COMT) gene, reporting that genetic variations in COMT which influence the brains levels of the neurotransmitter dopamine -- also determined the extent of an individuals placebo response.

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The Placebome: Where Genetics and the Placebo Effect Meet

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