title: Effects of expectation on placebo-induced dopamine release in Parkinson disease.
abstract: BACKGROUND
  Expectations play a central role in the mechanism of the placebo effect. In Parkinson disease (PD), the placebo effect is associated with release of endogenous dopamine in both nigrostriatal and mesoaccumbens projections, yet the factors that control this dopamine release are undetermined.
  
  
  OBJECTIVE
  To determine how the strength of expectation of clinical improvement influences the degree of striatal dopamine release in response to placebo in patients with moderate PD.
  
  
  METHODS
  Randomized, repeated-measures study with perceived expectation as the independent between-subjects variable.
  
  
  METHODS
  University of British Columbia Hospital, Vancouver, British Columbia, Canada. Patients Thirty-five patients with mild to moderate PD undergoing levodopa treatment. Intervention Verbal manipulation was used to modulate the expectations of patients, who were told that they had a particular probability (25%, 50%, 75%, or 100%) of receiving active medication when they in fact received placebo.
  
  
  METHODS
  The dopaminergic response to placebo was measured using [11C]raclopride positron emission tomography. The clinical response was also measured (Unified Parkinson Disease Rating Scale) and subjective responses were ascertained using patient self-report.
  
  
  RESULTS
  Significant dopamine release occurred when the declared probability of receiving active medication was 75%, but not at other probabilities. Placebo-induced dopamine release in all regions of the striatum was also highly correlated with the dopaminergic response to open administration of active medication. Whereas response to prior medication was the major determinant of placebo-induced dopamine release in the motor striatum, expectation of clinical improvement was additionally required to drive dopamine release in the ventral striatum.
  
  
  CONCLUSIONS
  The strength of belief of improvement can directly modulate dopamine release in patients with PD. Our findings demonstrate the importance of uncertainty and/or salience over and above a patient's prior treatment response in regulating the placebo effect and have important implications for the interpretation and design of clinical trials.
authors.affiliation: Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Lidstone
authors.forename: Michael
authors.initials: M
authors.lastname: Schulzer
authors.forename: Katherine
authors.initials: K
authors.lastname: Dinelle
authors.forename: Edwin
authors.initials: E
authors.lastname: Mak
authors.forename: Vesna
authors.initials: V
authors.lastname: Sossi
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Ruth
authors.forename: Raul
authors.initials: R
authors.lastname: de la Fuente-Fernández
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Phillips
authors.forename: A Jon
authors.initials: AJ
authors.lastname: Stoessl
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D001294:Attitude to Health; D001479:Basal Ganglia / Q000000981:diagnostic imaging; D001955:British Columbia; D002986:Clinical Trials as Topic / Q000379:methods; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism*; D015990:Placebo Effect; D010919:Placebos; D049268:Positron-Emission Tomography; D020891:Raclopride; D012107:Research Design; D012201:Reward
chemical_list: D000978:Antiparkinson Agents; D010919:Placebos; D020891:Raclopride; D007980:Levodopa; D004298:Dopamine