The Fault, Dear Brutus, Is Not in the Stars But in Our Genes

There’s an article at The Economist that takes note of a study that has suggested that the placebo effects varies from individual to individual and may be governed by our genes:

One thing that is known about the placebo effect is that it involves several brain systems, each under the control of a particular type of messenger molecule, called a neurotransmitter. These systems, like everything else in the body, are regulated by genes. This has led some researchers to ask whether different versions of the genes in question might modulate a person’s susceptibility to placebos.

A review of these researchers’ studies, published recently in Trends in Molecular Medicine by one of them, Kathryn Hall of Harvard Medical School, and her colleagues, suggests genes do indeed seem to matter. Dr Hall looked for links between the placebo effect’s strength and certain mutations, known as single nucleotide polymorphisms (SNPs), in which a single DNA “letter” in a gene is changed. Altogether she found 11 genes, in four neurotransmitter systems, where SNPs made a difference. Five were in the system mediated by dopamine, which includes the brain’s reward centres. Four were in the system mediated by serotonin, which regulates mood. And the opioid and endocannabinoid systems had one each.

As their names suggest, these two systems are affected respectively by opium and its derivatives, and by cannabis and its. The other two are affected by cocaine, which blocks the retrieval of dopamine into nerve cells, thus increasing its power as a messenger; and Prozac, which has the same effect on serotonin, and is used as an antidepressant. It is not hard to imagine a similarity between the workings of these drugs and what happens in the brain when the placebo effect is operating.

The genes for which most placebo-related SNP evidence exists encode enzymes called catechol-O-methyltransferase and monoamine oxidase. Both of these are parts of the dopamine system, and both are responsible for metabolising dopamine, and thus regulating the amount of it around. (Indeed, monoamine oxidase is the target of a second type of antidepressant, which has a different mechanism from Prozac.) People with different versions of either of these genes experience the placebo effect to different degrees. These various versions, moreover, are all commonplace, suggesting differences in placebo perception may be widespread.

That’s not a surprise to me. I have observed in myself that I don’t tend to exhibit much placebo effect. I’m a skeptic. Add to that my family’s common experience of unusual or even perverse reactions to drugs and it’s easy to understand why we might be wary of them. It’s pretty discouraging when the post-surgical painkiller prescribed by your physician induces excruciating pain.