Review supports existence of the 'placebome'

Some people may be genetically more likely to experience the 'placebo effect', according to a review of recent studies.

The paper, published in Trends in Molecular Biology, finds that research over the last decade implicates genetics in the placebo effect, primarily through influences on neurotransmitters and the way the brain responds to pain and reward.

'Genetic sequencing is revealing that the placebo response is, in fact, a complex phenotype with an unfolding physiology,' said lead author Dr Kathryn Hall from Program in Placebo Studies (PiPS) at Beth Israel Deaconess Medical Center and Harvard Medical School, USA.

'The study of genomic effects on the placebo response - what we call "the placebome" - is in its infancy, but there is already ample evidence that genetic variations in the brain's neurotransmitter pathways modify placebo effects.'

The first evidence for this came in 2012, when Dr Hall and her team published research in PLoS One exploring the genetics of catechol-O-methyltransferase (COMT), an enzyme that controls dopamine production in the brain and is connected to pain and pleasure.

Patients with irritable bowel syndrome were either put on a waiting list for treatment, given fake acupuncture by an unfriendly provider or fake acupuncture by a warm and caring provider.

The researchers then tested patients to see which version of the COMT gene they had. Patients with a high-dopamine variant of the gene were more likely to report that placebo treatment had improved their symptoms than patients with a low-dopamine variant of the gene - a response that was even greater when they were treated by a caring practitioner.

However, based on their current review, the team say that COMT is likely to represent just one gene and one neurotransmitter pathway involved in the placebo effect. They say that their round-up of the evidence supports the existence of a so-called 'placebome' - a network of genes involved in determining an individual's response to placebo.

'Our findings strongly support the idea that genetic signatures for placebo responses exist, but our findings are preliminary,' Dr Hall told Reuters. 'Something is definitely there, but more needs to be known.'

The team say that as knowledge of placebos increases, it may allow for those who respond to placebos to require smaller doses of treatment. This personalised approach to drug dosages could improve the experience of treatment for many patients, and they may experience fewer side effects.

The researchers also speculate that the findings could mean that the design of clinical trials will have to be changed in future to include a group that receives no treatment in addition to a group that receives a placebo, in order to gauge the magnitude of the placebo effect.

'As we think about personalised medicine… I think it's important that we don't forget the element that comes from the placebo response,' Dr Hall told Reuters. 'In a way, it's the most well studied treatment that has never been studied.'