To get a drug to market, pharmaceutical companies have to show that it works better than a placebo. But sometimes the placebo is just as powerful as the real thing. Just why our bodies respond so strongly to fake medicine has long been a mystery, but researchers are a step closer to solving that riddle, having picked out a particular gene that may be responsible for one type of placebo effect.
The placebo effect works because patients believe they are actually receiving treatment. Expecting treatment is similar to anticipating reward, studies have shown, and reward anticipation triggers the release of the neurotransmitter dopamine in the brain, which can help alleviate symptoms of chronic pain and depression. But what about placebo effects for other conditions?
Tomas Furmark, a psychologist at Uppsala University in Sweden, suspected that a different neurotransmitter plays a role in placebo responses to social anxiety disorder (SAD)--an abnormal fear of being judged by others. Brain imaging studies have shown that the amygdala, an area of the brain that regulates the fear response, is unusually active in patients with SAD. What's more, healthy people with certain variations of two genes that regulate the neurotransmitter serotonin have more active amygdalas.
Based on these results, Furmark and his colleagues--in collaboration with the pharmaceutical company GlaxoSmithKline--ran a placebo-controlled trial with 108 patients who had been previously diagnosed with SAD. The volunteers were randomly assigned to receive either a new serotonin medication or a sugar pill for 8 weeks. At the beginning of the trial, the patients had to prepare and deliver a speech in front of small group of people--an anxiety-triggering event--while the researchers tracked their amygdala activity using positron emission tomography. The technique allows researchers to track blood flow--and thus activity--in different areas of the brain. The study participants had to give a similar speech at the end of the treatment period, so researchers could assess whether their patterns of brain activity had changed.
Even sugar was enough to conquer some cases of SAD. Of the 25 patients who received the placebo, 10 reported reduced anxiety by the end of the study. (Numbers for the treatment group were not released because the trial is ongoing.) Brain scans during the second speech showed their amygdalas were also less active. Genetic analysis revealed that eight people who got relief from the placebo had a particular version of a gene that regulates serotonin production called the tryptophan hydroxylase-2 promoter (TPH2), the researchers report tomorrow in the Journal of Neuroscience. This is one of the same genetic variants linked to heightened amygdala activity in healthy people. TPH2 is the first genetic marker tied to any placebo response, the team reports.
Finding genetic markers for the placebo effect could raise ethical questions about how companies design their clinical trials, Furmark says. For example, "it could be tempting to screen all individuals and ... select only those with [the] nonresponsive phenotype [for the trial]."
Psychiatrist Helen Mayberg of Emory University in Atlanta, Georgia, who has studied the placebo effect in depression, agrees that the findings could have major implications for research design. But first, more research is needed to determine if the genetic markers for placebo relief from SAD can be generalized to other diseases, and what other genes might contribute to the phenomena, she says.