Placebo effect genes identified

Researchers have identified at least 11 genes that influence individuals’ susceptibility to the placebo effect.

Scientists from Harvard Medical School believe that these genes, collectively known as the placebome, may justify the use of genetic screening for placebo susceptibility. This could lead to more personalised treatments for symptoms of conditions that seemed to be relieved by placebo in some patients. These include pain syndromes, migraine, depression, irritable bowel syndrome and Parkinson’s disease. The discovery may also lead to the design of more balanced clinical trials, with genetic information used to spread placebo responders evenly between drug and control groups, for example.

The 11 genes implicated in the placebo response are all involved in known neurotransmitter pathways, according to an article in New Scientist. These include the opioid, endocannabinoid, dopaminergic and serotonin pathways.

One of the genes involved is that which encodes for catechol-O-methyltransferase (COMT), an enzyme that breaks down dopamine. Up to a quarter of caucasians carry two copies of the mutated COMT gene, which results in higher dopamine levels. Possession of two copies has been linked to a stronger placebo response in people suffering from irritable bowel syndrome.

Genetic screening for such polymorphisms could allow dose tailoring of analgesic drug therapy, for example. Individuals with COMT mutations allowed to self-administer their own post-operative analgesic via a morphine pump have been shown to give themselves lower doses. Lower doses in these patients could therefore prove effective with a reduced risk of side effects.

Around one-third of the population are thought to be placebo responders and this group of individuals have been shown to share some personality traits. A paper published in the Journal of Sports Science & Medicine linked extroversion, agreeableness, openness and neuroticism to placebo responsiveness. The study compared cyclists’ performance after being given either caffeine or a placebo and found that while responders might experience effects such as pain tolerance and fatigue resistance, interestingly, these were not always reflected in objective performance measures.

Brain scans also reveal differences between placebo responders and non-responders. Several brain structures are more or less active before and during a painful stimulus in those who experience a placebo effect. In responders, activity drops in areas processing pain and increases in areas involved in emotion, suggesting that the placebo alters the interpretation of pain rather than blocking pain signals to the brain.

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Citation
The Pharmaceutical Journal, April 2015;Online:DOI:10.1211/PJ.2015.20068370