Thursday, December 04, 2008

Journal Of Neurosciencence - Genotype Influences Placebo Responsiveness


Wow, who would have thought this is true? Whether or not a person responds to placebo depends upon having the right genes switched on. This is geek stuff, but it's interesting.
Genotype Influences Placebo Responsiveness

Tomas Furmark, Lieuwe Appel, Susanne Henningsson, Fredrik Åhs, Vanda Faria, Clas Linnman, Anna Pissiota, Orjan Frans, Massimo Bani, Paolo Bettica, Emilio Merlo Pich, Eva Jacobsson, Kurt Wahlstedt, Lars Oreland, Bengt Långström, Elias Eriksson, and Mats Fredrikson

Placebos can have impressive effects, from attenuating or enhancing pain to increasing mobility in Parkinson's disease patients. How otherwise inert substances can induce such effects is an intriguing question, so what was once a control condition has become the subject of many investigations. A subject's expectations about treatment outcome are important in the effectiveness of a placebo, and imaging studies reveal that, in subjects that respond to placebos, the placebo activates many of the same brain regions targeted by the active drug. This week, Furmark et al. report that a subject's genotype may also determine the effectiveness of placebo. Subjects with social anxiety disorder underwent functional neuroimaging while giving a short speech before and after sustained placebo treatment. Placebo responsiveness (i.e., reduced scores on anxiety tests) was correlated with reduced activity in the amygdala. Remarkably, responsiveness also depended on which alleles of two serotonin-related genes the subject had.
This certainly isn't conclusive evidence for a genetic link to the placebo response, but it is a useful indicator for the direction of further research.

Here's more from the New Scientist:

FOR the first time, a gene is being linked to increased susceptibility to the placebo effect, the mysterious capacity some people have to benefit from sham treatments.

The gene might not play a role in our response to treatment for all conditions, and the experiment involved only a small number of people. Nonetheless, the discovery is a milestone in the quest to understand this phenomenon, which often blurs the results of clinical trials "To our knowledge, it's the first time anyone has linked a gene to the placebo effect," says Tomas Furmark of Uppsala University in Sweden.

He and his colleagues recruited 25 people with an exaggerated fear of public humiliation, otherwise known as social anxiety disorder. Participants had to give a speech at the start and end of an eight-week treatment - which unbeknownst to them and their doctors, was actually a placebo.

Ten volunteers responded to the placebo much better than the rest. By the end of the experiment, their anxiety scores had halved, whereas the others' stayed the same. Brain scans also showed that activity in the amygdala, the brain's "fear" centre, had dropped by 3 per cent.

To see if there were genetic differences between responders and non-responders, Furmark screened them for a variant of the gene for tryptophan hydroxylase-2, which makes the brain chemical, serotonin. Previous studies suggested that people with two copies of a particular "G" variant are less anxious in standard "fear" tests. Sure enough 8 of the 10 responders had two copies, while none of the non-responders did (Journal of Neuroscience (DOI: 10.1523/JNEUROSCI.2534-08.2008).

Furmark believes the effect of the gene may extend to other conditions where the amygdala is involved, such as phobias, pain disorders and even depression. However, he cautions that only further studies will reveal whether the gene influences the placebo effect more generally.

This discovery could lead to treatments for disorders involving the amygdala, such as PSTD and other anxiety issues. Very cool.


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