A recent article in the British Medical Journal reports that, in a survey of almost 700 US internists and rheumatologists, about half admitted to prescribing placebo treatments on a regular basis. Surveys from other countries, including Denmark, the UK, Sweden and New Zealand produced similar results. The placebo effect (a positive clinical outcome not attributable to any known property of the treatment) is usually thought to be the result of positive expectation or belief. The reasons for placebo treatments in modern day medicine are complex, but many doctors appear to believe that such treatments may have beneficial clinical effects in some individuals, despite the lack of scientific evidence.
In a study published in the Journal of Neuroscience scientists have now found a biochemical pathway that contributes to the placebo effect, and explains why some people respond better than others. Imaging techniques were used to look at brain activity in the amygdala of patients with social anxiety disorder when they were asked to give a talk in public. The amygdala is associated with emotions, including fear and anxiety, and increased activity in this area of the brain would be expected during stressful activities such as public speaking. The study showed that some of the patients responded to placebo treatment whilst others did not. Those patients who benefited were found to have reduced activity in the amygdala, whilst those patients who did not respond had no such reduction.
The study was also able to link two genes that influence the reuptake and synthesis of serotonin (the serotonin transporter gene and the tryptophan hydroxylase-2 gene) with a positive placebo response. Only individuals with certain variants of these genes had reduced activity in the amygdala and reduced anxiety. The presence of particular tryptophan hydroxylase-2 gene variants was found to be especially predictive of the effectiveness of the placebo. The identification of a genetic marker for placebo sensitivity could have important implications for the design of clinical trials in which the effect of a placebo is ‘subtracted’ from that of a new test drug to determine effectiveness.