Altered Relationship Between Hippocampal Glutamate Levels and Striatal Dopamine Function in Subjects at Ultra High Risk of Psychosis

James M. Stone, Oliver Howes, Alice Egerton, Joseph Egerton, Paul Allen, David J. Lythgoe, Ruth O'Gorman, Mary A. McLean, Gareth J. Barker, Philip McGuire

Research output: Contribution to journalArticle


Background: Animal models of psychosis propose that striatal hyperdopaminergia is driven by abnormalities in hippocampal glutamatergic neurotransmission, but this has never been tested in humans.Methods: Sixteen individuals with an at-risk mental state for psychosis (ARMS) and 12 control subjects underwent proton magnetic resonance spectroscopy to estimate hippocampal glutamate and [18F]DOPA positron emission tomography to index striatal dopamine function. The relationship between hippocampal glutamate and striatal dopamine, as well as their relationship with prodromal symptoms, was determined using linear regression.Results: In ARMS subjects, but not controls, there was a significant negative relationship between hippocampal glutamate levels and striatal [18F]DOPA uptake (p = .03). Within the ARMS sample, striatal [18F]DOPA uptake was correlated with severity of abnormal beliefs (p = .03), there was a trend for hippocampal glutamate levels to be correlated with disordered speech (p = .06) and a trend for the interaction between hippocampal glutamate and [18F]DOPA uptake to predict later transition to psychosis (p = .07).Conclusions: The relationship between hippocampal glutamate and striatal dopamine systems is altered in people at high risk of psychosis, and the degree to which it is changed may be related to the risk of transition to psychosis. Pharmacologic modulation of the glutamate system before the onset of psychosis might ameliorate this risk.
Original languageEnglish
Pages (from-to)599-602
JournalBiological Psychiatry
Issue number7
Publication statusPublished - 2010

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