Do Genes Affect How You Respond to a Placebo

When I wrote about the placebo effect a couple of months ago, scientists didn't have any real understanding of why placebo works for some people but not others. Some patients can think themselves out of pain (the best-known placebo effect), but others cannot. Some patients with Parkinson's disease can take a sugar pill and, through the power of belief and hope, see their symptoms improve—but not all. Some patients, having experienced the respiration-depressing effects of morphine, will find their breathing becoming shallower even when they're injected with an inert solution, not morphine; others experience no such placebo effect. The difference, it turns out, may come down to the levels of particular neurotransmitters that carry messages through the brain, and those levels may reflect genetic differences.

In the August issue of the Journal of Clinical Psychopharmacology, scientists led by Andrew Leuchter of UCLA will report that in patients with major depressive disorder, variants of two genes affect whether someone will respond to a placebo. (The genes have no effect on whether someone will develop major depression in the first place.)

The genes that matter are those that make enzymes called catechol-O-methyltransferase (COMT) and monoamine oxidase A (MAO-A). That makes sense if you believe that one way the placebo effect works is by goosing the brain's natural reward pathways. Those pathways run on two neurotransmitters, dopamine and norepinephrine. "Most research on how placebos work now focuses on the brain's reward system and on dopamine signals," Leuchter told me by e-mail. "Our work suggests that norepinephrine should be examined as well. Dopamine and norepinephrine actually work hand-in-hand to manage reward information. One way to think of it is that dopamine helps an individual expect a reward, and norepinephrine helps you sustain attention on the possible reward and figure out how it can be achieved. We theorize that a person has to have the optimal level of norepinephrine in order to sustain the placebo response." COMT breaks down dopamine; MAO-A breaks down norepinephrine. The scientists therefore guessed that levels or forms of these enzymes would affect brain levels of the reward chemicals and thus whether that brain is more or less likely to respond to a placebo.

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