The Placebo Effect, where patients derive benefit from a "dummy" pill, has been described many times over the years. New research shows that there is a genetic basis for the placebo effect in sufferers of social anxiety disorder.

The Placebo Effect is a well described phenomenon wherein patients given only a "dummy" pill, or placebo, nevertheless experience an improvement in their symptoms. Placebo effects have been described for a wide variety of diseases with some experts estimating that up to 90% of medical disorders benefit from a placebo effect. In some controversial cases, such as selective serotonin reuptake inhibitor (SSRI) anti-depressants, placebo effects are thought to account for a major proportion of the positive effects of a drug.

A recent paper by Mats Fredikson and colleagues at Uppsala University, published in the Journal of Neuroscience, describes how a person's genes may determine whether or not they experience a placebo effect. The study was conducted using sufferers of social anxiety disorder. One of the major symptoms of social anxiety disorder is a fear of negative evaluation by others. A classic example is that sufferers show a strong fear of public speaking.

In the Frederikson study, social anxiety disorder sufferers were asked to engage in a stressful public speaking event. They were then "treated" for 8 weeks (with placebo) and then again asked to speak in public. 40% of the placebo-treated patients showed an improvement in their symptoms over the 8 week period. Symptoms were rated by psychiatrists.

A key area of the nervous system involved in the generation and control of fear is the amygdala, a small, almond shaped part of the brain. When anyone gets scared or stressed, their amygdala becomes activated. Multiple human imaging studies have revealed that, when sufferers of social anxiety disorder become stressed, their amygdala shows a greater activation than that of non-sufferers. However, when social anxiety disorder patients are successfully treated, such as with cognitive behavioral therapy or citalopram, their amygdala function is restored to normal. In the Frederikson study, placebo-treated patients who experienced a reduction in their social anxiety disorder symptoms also showed a reduction in their amygdala activation.

Among the most common therapies for social anxiety disorders are SSRI's, which work in part by increasing the abundance of serotonin in certain parts of the brain (including the amygdala). The Uppsala team analyzed two genes that control the natural synthesis and reuptake of serotonin. Like all genes, subtle variants exist in some people. The most fascinating finding was that the patients who responded best to placebo carried different variants of these serotonin-related genes compared to those that did not respond to placebo. The icing on the cake was that one variant, in a gene called tryptophan-hydroxylase-2 (TPH2) could predict whether a person would respond to placebo. That is to say, if a sufferer of social anxiety disorder were to be tested and found to carry this variant of TPH2, then they would probably benefit from placebo treatment.

This study provides further stunning evidence of the power of genetic analysis, as well as providing some molecular and genetic explanations for the placebo effect. It may also provide some new clues into understanding the controversies surrounding SSRI treatment, which is often claimed to be no better than placebo. The powerful placebo effect in some people may make it harder to see a significant difference between placebo and SSRI-treated groups, even though the SSRI drugs may be having beneficial effects in patients who do not carry the "placebo genes".

Full study; Furmark et al, A Link between Serotonin-Related Gene Polymorphisms, Amygdala Activity, and Placebo-Induced Relief from Social Anxiety. The Journal of Neuroscience, December 3, 2008, 28(49):13066-13074.

About the Author

Phil Newton

Phil Newton, Ph.D., is the Head of Learning and Teaching for the College of Medicine at Swansea University.

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