Dopamine and Glutamate in Antipsychotic-Responsive Compared With Antipsychotic-Nonresponsive Psychosis: A Multicenter Positron Emission Tomography and Magnetic Resonance Spectroscopy Study (STRATA)

Alice Egerton, Anna Murphy, Jacek Donocik, Adriana Anton, Gareth J Barker, Tracy Collier, Bill Deakin, Richard Drake, Emma Eliasson, Richard Emsley, Catherine J Gregory, Kira Griffiths, Shitij Kapur, Laura Kassoumeri, Laura Knight, Emily J B Lambe, Stephen M Lawrie, Jane Lees, Shôn Lewis, David J LythgoeJulian Matthews, Philip Mcguire, Lily Mcnamee, Scott Semple, Alexander D Shaw, Krish D Singh, Charlotte Stockton-powdrell, Peter S Talbot, Mattia Veronese, Ernest Wagner, James T R Walters, Stephen R Williams, James H Maccabe, Oliver D Howes

Research output: Contribution to journalArticle

Abstract

The variability in the response to antipsychotic medication in schizophrenia may reflect between-patient differences in neurobiology. Recent cross-sectional neuroimaging studies suggest that a poorer therapeutic response is associated with relatively normal striatal dopamine synthesis capacity but elevated anterior cingulate cortex (ACC) glutamate levels. We sought to test whether these measures can differentiate patients with psychosis who are antipsychotic responsive from those who are antipsychotic nonresponsive in a multicenter cross-sectional study. 1H-magnetic resonance spectroscopy (1H-MRS) was used to measure glutamate levels (Glucorr) in the ACC and in the right striatum in 92 patients across 4 sites (48 responders [R] and 44 nonresponders [NR]). In 54 patients at 2 sites (25 R and 29 NR), we additionally acquired 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine (18F-DOPA) positron emission tomography (PET) to index striatal dopamine function (Kicer, min−1). The mean ACC Glucorr was higher in the NR than the R group after adjustment for age and sex (F1,80 = 4.27; P = .04). This was associated with an area under the curve for the group discrimination of 0.59. There were no group differences in striatal dopamine function or striatal Glucorr. The results provide partial further support for a role of ACC glutamate, but not striatal dopamine synthesis, in determining the nature of the response to antipsychotic medication. The low discriminative accuracy might be improved in groups with greater clinical separation or increased in future studies that focus on the antipsychotic response at an earlier stage of the disorder and integrate other candidate predictive biomarkers. Greater harmonization of multicenter PET and 1H-MRS may also improve sensitivity
Original languageEnglish
Number of pages12
JournalSchizophrenia Bulletin
Early online date10 Sep 2020
DOIs
Publication statusE-pub ahead of print - 10 Sep 2020
Externally publishedYes

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