Placebo and Pain Chapter 10. Brain Predictors of Individual Differences in Placebo Responding

Placebo responses are highly variable across individuals. Explaining this variability is one of the keys to understanding endogenous regulatory processes, and is critical for measuring and controlling placebo effects in all kinds of studies. In this chapter, we review literature on the personality and brain correlates of individual differences in placebo analgesia. An emerging brain literature has used functional magnetic resonance imaging (fMRI), opioid binding, dopamine binding, and structural brain imaging to predict the magnitude of individual placebo responses. Brain predictors in prefrontal cortices and ventral striatum/nucleus accumbens are relatively consistent across studies and methodologies, showing promise for understanding the neural bases of placebo analgesia. However, most studies use voxel-wise correlation maps to relate brain measures and placebo analgesia, which do not provide unbiased measures of predictive accuracy. Thus, the utility of these brain measures remains to be determined by larger-scale studies using appropriate analytic methods. Finally, we address an apparent paradox in the placebo literature: placebo responses appear to be both related to stable person-level variables (e.g. brain structure, genetics, personality) and highly variable across situational contexts. We suggest that a resolution lies in recognizing that placebo responses, like many other psychologic phenomena, arise from person × situation interactions, and that both must be considered jointly in order to understand and predict who will be a placebo ‘responder’ in a given situation.