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
Howes, Oliver D; Bonoldi, Ilaria; McCutcheon, Robert A; Azis, Matilda; Antoniades, Mathilde; Bossong, Matthijs; Modinos, Gemma; Perez, Jesus; Stone, James M; Santangelo, Barbara; Veronese, Mattia; Grace, Anthony; Allen, Paul; McGuire, Philip K
(2020) Neuropsychopharmacology, volume 45, issue 4, pp. 641 - 648
(Article)
Abstract
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
... read more
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.
show less
Download/Full Text
Keywords: Pharmacology, Psychiatry and Mental health
ISSN: 0893-133X
Publisher: Nature Publishing Group
Note: Funding Information: This study was funded by Medical Research Council-UK, and Wellcome Trust grants and the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. Dr Howes has received investigator-initiated research funding from and/or participated in advisory/speaker meetings organised by Angellini, Astra-Zeneca, Autifony, Biogen, BMS, Eli Lilly, Heptares, Jansenn, Lundbeck, Lyden-Delta, Otsuka, Servier, Sunovion, Rand and Roche. Neither Dr Howes nor his family have been employed by or have holdings/a financial stake in any pharmaceutical company. The other authors have no relevant conflicts of interest. Publisher Copyright: © 2019, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
(Peer reviewed)