The word placebo, Latin for "I shall please", received its first medical reference in 1811, when it was defined as "any medicine adapted more to please than to benefit the patient"1. More recently, placebo use has become most common in clinical studies to determine the effectiveness of the actual medication given to other patients in the study. Usually simply a sugar pill, the placebo is given to participants meant to represent the 'no treatment' group. Yet, for some people, the placebo works nearly as well as the actual medication - this phenomenon is known as the "placebo effect". How well placebos work varies widely among individuals. Why they work at all remains a mystery, thought to be based upon some combination of biological and psychological factors.

A team of researchers at UCLA believe they have the answer - genetics. Dr. Andrew Leuchter, a professor of psychiatry at the UCLA Semel Institute for Neuroscience and Human Behavior, and colleagues report that in people suffering from major depressive disorder, or MDD, genes that influence the brain's reward pathways may modulate the response to placebos. The research appears in the August edition of the Journal of Clinical Psychopharmacology.

Placebos are believed to act by causing a release of "feel good" chemicals that stimulate the brain's central reward pathways. These brain chemicals - specifically dopamine and norepinephrine - are a class of neurotransmitters called monoamines, and it turns out the chemical signaling done by monoamines is under strong genetic control. The researchers hypothesized that common genetic variations between individuals could influence the placebo response.

The researchers took blood samples from 84 people diagnosed with MDD; 32 were given medication and 52 a placebo. The researchers looked at the polymorphisms in genes that coded for two enzymes that regulate monoamine levels: catechol-O-methyltransferase (COMT) and monoamine oxidase A (MAO-A). Subjects with the highest enzyme activity within the MAO-A polymorphism had a significantly lower placebo response than those with other genotypes. With respect to COMT, those with lower enzyme activity within this polymorphism had a lower placebo response.

"Our findings suggest that patients with MDD who have specific MAO-A and COMT genotypes may be biologically advantaged or disadvantaged in mounting a placebo response, because of the activity of these two enzymes," said Leuchter, who directs the Laboratory of Brain, Behavior and Pharmacology at the UCLA Semel Institute.

"To our knowledge, this is the first study to examine the association between MAO-A and COMT polymorphisms and a response to placebo in people who suffer from major depressive disorder," he said.

Leuchter noted that this is not the sole explanation for a response to a placebo, which is likely to be caused by many factors, both biological and psychosocial. "But the data suggests that individual differences in response to placebo are significantly influenced by individual genotypes," he said.

Including the influence of genotype in the design of clinical trials could facilitate more powerful testing of future treatments, Leuchter said.

Source: http://www.newsroom.ucla.edu/portal/ucla/first-genetic-evidence-for-why-...

1. Shapiro AK. (1968) Semantics of the placebo. Psychiatr Q. 42:653-95.