Dr. Andrew Leuchter, a professor of psychiatry at the UCLA Semel Institute for Neuroscience and Human Behavior, has found that in people suffering from major depressive disorder (MDD), genes that influence the brain's reward pathways may modulate the response to placebos.
Writing about their work in the the Journal of Clinical Psychopharmacology, the researchers point out that placebos are thought to act by stimulating the brain's central reward pathways by releasing a class of neurotransmitters called monoamines, specifically dopamine and norepinephrine.
These are the brain chemicals that make us "feel good", they say in the report.
As the chemical signaling done by monoamines is under strong genetic control, the scientists reasoned that common genetic variations between individuals - called genetic polymorphisms - could influence the placebo response.
During the study, the research team took blood samples from 84 people diagnosed with MDD. They gave 32 persons medication, and 52 a placebo.
The researchers then 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).
They observed that the people who had the highest enzyme activity within the MAO-A polymorphism had a significantly lower placebo response than those with other genotypes.
With respect to COMT, according to the researchers, 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 concedes 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.
He believes that including the influence of genotype in the design of clinical trials could facilitate more powerful testing of future treatments.