Placebo Response Under Genetic Control

Prozac, a selective serotonin reuptake inhibit...

Monoamine Oxidase A and Catechol-O-Methyltransferase Functional Polymorphisms and the Placebo Response in Major Depressive Disorder: “The placebo response shows pronounced interindividual variability. Placebos are postulated to act through central reward pathways that are modulated by monoamines. Because monoaminergic signaling is under strong genetic control, we hypothesized that common functional polymorphisms modulating monoaminergic tone would be related to degree of improvement during placebo treatment of subjects with major depressive disorder. We examined polymorphisms in genes encoding the catabolic enzymes catechol-O-methyltransferase and monoamine oxidase A. Subjects with monoamine oxidase A G/T polymorphisms (rs6323) coding for the highest activity form of the enzyme (G or G/G) had a significantly lower magnitude of placebo response than those with other genotypes. Subjects with Val158Met catechol-O-methyltransferase polymorphisms coding for a lower-activity form of the enzyme (2 Met alleles) showed a statistical trend toward a lower magnitude of placebo response. These findings support the hypothesis that genetic polymorphisms modulating monoaminergic tone are related to degree of placebo responsiveness in major depressive disorder.” (Journal of Clinical Psychopharmacology)

Some behavioral scientists consider the placebo response to be a nuisance that confounds psychopharmacological research; patients get better even when they do not get the active drug. Some of us, however, feel that the placebo response is a good friend of clinical psychiatry. Some meta-analyses of antidepressant efficacy studies suggest that the medications may not be that effective and that much of the therapeutic response to antidepressants may in fact be ascribable to the placebo response. (The psychiatrist’s role, as a corollary, may be not the art of picking a drug to prescribe but enlisting the individual into a mindset that mobilizes their self-healing capacities.) We already know that depression is related to the reward circuitry in the brain and that genetic susceptibility to depressive disorders relates to polymorphism in the catecholamine system. If the placebo response as well varies with differences in that circuitry, could it be that those patients with lower capacity for the placebo response could also be those patients prone to become depressed int he first place? If we cannot as effectively mobilize their placebo response when they are in the placebo wing of a drug study, perhaps they cannot as effectively bring self-suggestion, affirmation and other coping strategies to bear on the distressing situations in their lives?