Glutamatergic and dopaminergic function and the relationship to outcome in people at clinical high risk of psychosis a multi.pdf (904.98 kB)
Glutamatergic and dopaminergic function and the relationship to outcome in people at clinical high risk of psychosis: a multi-modal PET-magnetic resonance brain imaging study
journal contribution
posted on 2023-06-10, 04:57 authored by Oliver D Howes, Ilaria Bonoldi, Robert A McCutcheon, Matlida Azis, Mathilde Antoniades, Mattijis Bossong, Gemma Modinos, Jesus Perez, James StoneJames Stone, Barbara Santangelo, Mattia Veronese, Anthony Grace, Paul Allen, Philip K McGuirePreclinical 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.
History
Publication status
- Published
File Version
- Published version
Journal
NeuropsychopharmacologyISSN
0893-133XPublisher
Springer Science and Business Media LLCExternal DOI
Volume
45Page range
641-648Event location
EnglandDepartment affiliated with
- BSMS Neuroscience Publications
Full text available
- Yes
Peer reviewed?
- Yes