Preclinical models of
psychosis propose that hippocampal glutamatergic neuron hyperactivity drives increased striatal dopaminergic activity, which underlies the development of psychotic symptoms. The aim of this study was to examine the relationship between hippocampal
glutamate and subcortical dopaminergic function in people at clinical high risk for
psychosis, and to assess the association with the development of psychotic symptoms. 1H-MRS was used to measure hippocampal
glutamate concentrations, and 18F-DOPA PET was used to measure
dopamine synthesis capacity in 70 subjects (51 people at clinical high risk for
psychosis and 19 healthy controls). Clinical assessments were undertaken at baseline and follow-up (median 15 months). Striatal
dopamine synthesis capacity predicted the worsening of psychotic symptoms at follow-up (r = 0.35; p < 0.05), but not transition to a
psychotic disorder (p = 0.22), and was not significantly related to hippocampal
glutamate concentration (p = 0.13). There were no differences in either
glutamate (p = 0.5) or
dopamine (p = 0.5) measures in the total patient group relative to controls. Striatal
dopamine synthesis capacity at presentation predicts the subsequent worsening of sub-clinical total and psychotic symptoms, consistent with a role for
dopamine in the development of psychotic symptoms, but is not strongly linked to hippocampal
glutamate concentrations.