11 June 2002

by Marc Seal m.seal@iop.kcl.ac.uk
 

Simply believing that medical treatment will be beneficial to your health is, in itself, enough to bring about a significant improvement in your well-being. Despite the omnipresent nature of this phenomenon the physiological mechanisms underlying the placebo effect are not well understood. Two recent PET investigations using innovative designs have provided exciting new information about the neuroanatomical foundations of the placebo effect.

Mayberg et al. compared changes in brain activity associated with successful improvement in mood due to administration of a placebo and antidepressant medication. Hospitalized patients with unipolar depression were randomly allocated to a placebo or antidepressant (SSRI) condition. PET scans of resting brain state were conducted before and after administration of placebo or medication at week 1 and week 6 of the trial. At the end of the trial equal numbers of successful treatment ‘responders’ were identified in both conditions (n=4). Subsequent analysis of the PET data revealed that successful response to the placebo and antidepressant medication were both associated with a common pattern of cortical activation (frontal-posterior cingulate). Successful responders to the antidepressant medication showed additional unique areas of activation. Given that placebo responders showed marked improvement in their mood, Mayberg et al. propose that the common areas of cortical activation might be necessary for the remission of the signs and symptoms of depression. In the other recent investigation, Petrovic et al. compared the brain systems involved with pain relief following the introduction of an opioid analgesia or placebo treatment. While being scanned, subjects were presented with painful stimuli of varying intensity and intravenously administered either opioid analgesia or placebo (saline). In order to establish the extent to which subjects demonstrated placebo analgesia at end of each scan subjects rated the intensity of the stimulus on a visual analogue scale. Comparison of the subjects’ cortical responses to pain found that opioid and placebo analgesia were associated with increased blood flow in the same areas involved in pain management and containing high numbers of opioid receptors. Further analysis suggested that individuals who reported relatively high levels of placebo analgesia showed greater activation of the opioid analgesia network.

These studies show that a successful placebo response involves the same cortical regions that are engaged with successful pharmacological intervention. However, both studies were characterized by marked inter-subject variability with respect to the magnitude of placebo response. Future research will need to establish to what extent this variability explains individual differences in treatment responsiveness to a range of pharmacological and psychological interventions.