Increased dopamine transmission in schizophrenia: Relationship to illness phases

Background: Abnormalities of dopamine function in schizophrenia are suggest ed by the common antidopaminergic properties of antipsychotic medications. However, direct evidence of a hyerdopaminergic stare in schizophrenia has b een difficult to demonstrate, given the difficulty to measure dopamine tran smission in the living human brain, Such evidence has recently emerged. Thr ee studies reported an increase in dopamine transmission following acute am phetamine challenge in patients with schizophrenia compared to matched heal thy control subjects, thus demonstrating a dysregulation of dopamine in sch izophrenia. In all studies, a large variance was observed within the schizo phrenic group in the magnitude of this finding, and clinical predictors of this effect could nor 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 ar e: 1) dysregulation of dopamine function revealed by the amphetamine challe nge 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 studi ed during a remission phase. Conclusions: A hyperdopaminergic state is present in schizophrenia during t he initial episode and subsequent relapses, but not in periods of remission . This finding has important consequences for the development of new treatm ent strategies for the remission phase. (C) 1999 Society of Biological Psyc hiatry.