Personality influences placebo response

Researchers have found that resilient, altruistic, and straightforward individuals are significantly more likely to respond to a sham painkilling or placebo injection than those who are angry and hostile.

The positive response to placebo seen in resilient individuals could be at least partially explained by activation of endogenous opioid neurotransmission in the brain, say the researchers.

If replicated in a larger sample, these findings suggest that the results of clinical trials could be adjusted for individual placebo response, and may also show how personality traits influence an individual's response to stressful situations

Jon-Kar Zubieta (University of Michigan, Ann Arbor, USA) and colleagues identified the strongest personality traits in each one of 50 healthy individuals aged 19-38 years by administering a battery of standard psychologic tests. Each individual then underwent positron emission tomography while they were told that their jaw muscle would be injected with salt water.

Each individual was also told that they would be injected with a painkiller - which was actually a placebo - at certain times, and were asked to rate how much relief they expected to feel before the injections began. During the 20-minute period that the participants received the injections, they were asked repeatedly how effective the "painkiller" was.

Statistical analysis showed that high scores for Ego-Resiliency, Altruism, and Straightforwardness traits on the personality tests were positive predictors for the placebo analgesic response, and a high combined score for the Anger and Hostility traits was a negative predictor. Together, these personality traits accounted for 25% of the variance in placebo analgesic response.

Molecular imaging revealed that subjects scoring above the median in a composite of these personality traits demonstrated a greater activation of the µ-opioid neurotransmission in the subgenual and dorsal anterior cingulated cortex (ACC), orbitofrontal cortex, insula, nucleus accumbens, amygdala, and periaqueductal gray (PAG) areas of the brain.

Endogenous opioid release in the dorsal ACC and PAG was positively associated with placebo-induced reductions in pain ratings.

Significant reductions in plasma cortisol levels were observed during placebo administration and were positively correlated with decreases in pain ratings and µ-opioid system activation in the dorsal ACC and PAG. There was a trend toward a negative association between plasma cortisol and Anger and Hostility score.

"We ended up finding that the greatest influence came from a series of factors related to individual resiliency, the capacity to withstand and overcome stressors and difficult situations. People with those factors had the greatest ability to take environmental information - the placebo - and convert it to a change in biology," explained Zubieta in a press statement.

The findings were reported in Neuropsychopharmacology.

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