Dopamine and Glutamate in Antipsychotic-Responsive Compared With Antipsychotic-Nonresponsive Psychosis: A Multicenter Positron Emission Tomography and Magnetic Resonance Spectroscopy Study (STRATA).
Adult
Antipsychotic Agents
/ pharmacology
Corpus Striatum
/ diagnostic imaging
Cross-Sectional Studies
Dopamine
/ metabolism
Female
Glutamic Acid
/ metabolism
Gyrus Cinguli
/ diagnostic imaging
Humans
Male
Middle Aged
Positron-Emission Tomography
Proton Magnetic Resonance Spectroscopy
Psychotic Disorders
/ diagnostic imaging
Schizophrenia
/ diagnostic imaging
Young Adult
1H-MRS
PET
antipsychotic response, treatment resistance
schizophrenia
Journal
Schizophrenia bulletin
ISSN: 1745-1701
Titre abrégé: Schizophr Bull
Pays: United States
ID NLM: 0236760
Informations de publication
Date de publication:
16 03 2021
16 03 2021
Historique:
pubmed:
11
9
2020
medline:
23
11
2021
entrez:
10
9
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32910150
pii: 5903699
doi: 10.1093/schbul/sbaa128
pmc: PMC7965076
doi:
Substances chimiques
Antipsychotic Agents
0
Glutamic Acid
3KX376GY7L
Dopamine
VTD58H1Z2X
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
505-516Subventions
Organisme : Medical Research Council
ID : G0701127
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U120097115
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L010305/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L011794/1
Pays : United Kingdom
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.
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