The Functional Neuroanatomy of the Placebo Effect

Abstract

The common pattern of cortical glucose metabolism increases and limbic-paralimbic metabolism decreases in placebo and fluoxetine responders suggests that facilitation of these changes may be necessary for depression remission, regardless of treatment modality. Clinical improvement in the group receiving placebo as part of an inpatient study is consistent with the well-recognized effect that altering the therapeutic environment may significantly contribute to reducing clinical symptoms. The additional subcortical and limbic metabolism decreases seen uniquely in fluoxetine responders may convey additional advantage in maintaining long-term clinical response and in relapse prevention.

Cellular changes in the postmortem hippocampus in major depression

“…Varying cortical pathology versus hippocampal pathology is not unexpected considering the unique normal functions and unique contributions of these regions to the psychopathology of depression. Other evidence of dissimilarities between prefrontal cortex and hippocampus in depression comes from the work of Mayberg and colleagues (Kennedy et al 2001;Mayberg et al 2000Mayberg et al , 2002. Successful clinical treatment (or even the use of placebo) in depression was associated with an increase in metabolism in prefrontal cortex and a decrease in metabolism in hippocampus.…”

Positron Emission Tomography of Regional Brain Metabolic Responses to a Serotonergic Challenge in Major Depressive Disorder with and without Borderline Personality Disorder

“…Alternatively, the effects of depression in this area may overpower those of impulsivity in BPD as some functional imaging studies have also suggested a role for the orbital prefrontal cortex in the pathophysiology of depression. For example, studies that examined abnormalities during a Major Depressive Episode and after various forms of treatment report normalization of orbitofrontal and anterior cingulate abnormalities with treatment (Baxter Jr et al, 1989;Bench et al, 1995;Brody et al, 1999;Buchsbaum et al, 1997;Mayberg et al, 2000Mayberg et al, , 2002. Indeed, Bremner et al (1997) found that depressed patients who were 6 weeks into a course of antidepressant treatment exhibited decreases in glucose metabolic rates in the orbitofrontal cortex and thalamus after a tryptophan-depletion-induced acute relapse compared to patients without depressive symptoms.…”

Biological Psychiatry Sketched—Past, Present, and Future

“…Apparently our social brains respond quite well to the sympathetic concerns of others, which may be the foundation of all pervasive placebo effects in psychiatry (Harrington 1999;Moerman 2002;Shapiro and Shapiro 2001). Of course, we now know that placebo effects have real effects on the brain (Mayberg et al, 2002), perhaps brain opioid mediated (Petrovic et al, 2002), and the intervening prosocial feelings may be mediated, in part, by endogenous opioids (Panksepp, 1998).…”