The functional neuroanatomy of the placebo effect.
OBJECTIVE
Administration of placebo can result in a clinical response indistinguishable from that seen with active antidepressant treatment. Functional brain correlates of this phenomenon have not been fully characterized.


METHODS
Changes in brain glucose metabolism were measured by using positron emission tomography in hospitalized men with unipolar depression who were administered placebo as part of an inpatient imaging study of fluoxetine. Common and unique response effects to administration of placebo or fluoxetine were assessed after a 6-week, double-blind trial.


RESULTS
Placebo response was associated with regional metabolic increases involving the prefrontal, anterior cingulate, premotor, parietal, posterior insula, and posterior cingulate and metabolic decreases involving the subgenual cingulate, parahippocampus, and thalamus. Regions of change overlapped those seen in responders administered active fluoxetine. Fluoxetine response, however, was associated with additional subcortical and limbic changes in the brainstem, striatum, anterior insula, and hippocampus, sources of efferent input to the response-specific regions identified with both agents.


CONCLUSIONS
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.
Mayberg
Helen S
HS
Department of Psychiatry, University of Texas at San Antonio, USA. hmayberg@rotman-baycrest.on.ca
Silva
J Arturo
JA
Brannan
Steven K
SK
Tekell
Janet L
JL
Mahurin
Roderick K
RK
McGinnis
Scott
S
Jerabek
Paul A
PA
D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D005473:Fluoxetine / Q000494:pharmacology / Q000627:therapeutic use; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008032:Limbic System / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015990:Placebo Effect; D010919:Placebos / Q000494:pharmacology / Q000627:therapeutic use; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D014055:Tomography, Emission-Computed
D005473:Fluoxetine; D005947:Glucose; D010919:Placebos; D017367:Selective Serotonin Reuptake Inhibitors