Increased dopamine transmission in schizophrenia: relationship to illness phases

Biol Psychiatry. 1999 Jul 1;46(1):56-72. doi: 10.1016/s0006-3223(99)00067-0.


Background: Abnormalities of dopamine function in schizophrenia are suggested by the common antidopaminergic properties of antipsychotic medications. However, direct evidence of a hyperdopaminergic state in schizophrenia has been difficult to demonstrate, given the difficulty to measure dopamine transmission in the living human brain. Such evidence has recently emerged. Three studies reported an increase in dopamine transmission following acute amphetamine challenge in patients with schizophrenia compared to matched healthy control subjects, thus demonstrating a dysregulation of dopamine in schizophrenia. In all studies, a large variance was observed within the schizophrenic group in the magnitude of this finding, and clinical predictors of this effect could not be identified.

Methods: In this paper, we combined previously published and newly acquired data to obtain sufficient power to address this question.

Results: The most important findings derived from this extended data set are: 1) dysregulation of dopamine function revealed by the amphetamine challenge is present at onset of illness and in patients never previously exposed to neuroleptic medications; 2) this dysregulation was observed in patients experiencing an episode of illness exacerbation, but not in patients studied during a remission phase.

Conclusions: A hyperdopaminergic state is present in schizophrenia during the initial episode and subsequent relapses, but not in periods of remission. This finding has important consequences for the development of new treatment strategies for the remission phase.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Adult
  • Amphetamines / blood
  • Amphetamines / pharmacokinetics
  • Brain / diagnostic imaging
  • Chromatography, High Pressure Liquid / methods
  • Cohort Studies
  • Corpus Striatum / metabolism
  • Dopamine / metabolism*
  • Female
  • Humans
  • Male
  • Predictive Value of Tests
  • Schizophrenia / diagnostic imaging
  • Schizophrenia / metabolism*
  • Schizophrenic Psychology
  • Severity of Illness Index
  • Sex Factors
  • Stress, Psychological / psychology
  • Synaptic Transmission / physiology*
  • Tomography, Emission-Computed
  • Tomography, Emission-Computed, Single-Photon


  • Amphetamines
  • Dopamine