ArticleSchizophrenia bulletin2021
Dopamine and Glutamate in Antipsychotic-Responsive Compared With Antipsychotic-Nonresponsive Psychosis: A Multicenter Positron Emission Tomography and Magnetic Resonance Spectroscopy Study (STRATA).
Article in Schizophrenia bulletin, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 6 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
54 citing papers in PubMed, 6 syntheses or guidelines pooled it, 94 citations in OpenAlex.
- Molecular and topographic mapping of antipsychotic effects: a meta-analysis of postsynaptic density proteins in animal models with translational implications.Molecular psychiatry · 2026Pooled it
- EANM perspective on clinical PET and SPECT imaging in schizophrenia-spectrum disorders: a systematic review of longitudinal studies.European journal of nuclear medicine and molecular imaging · 2025Pooled it
- Glutamatergic neurotransmission in schizophrenia: A systematic review and quantitative synthesis of proton magnetic resonance spectroscopy studies across schizophrenia spectrum disorders.The Australian and New Zealand journal of psychiatry · 2024Pooled it
- Variability and magnitude of brain glutamate levels in schizophrenia: a meta and mega-analysis.Molecular psychiatry · 2023Pooled it
- Rational and Translational Implications of D-Amino Acids for Treatment-Resistant Schizophrenia: From Neurobiology to the Clinics.Biomolecules · 2022Pooled it
- Pooled it
- The relationship between glutamate, dopamine, and cortical gray matter: A simultaneous PET-MR study.Molecular psychiatry · 2022Trial
- Polygenic risk meets early trauma: toward a neuropsychodevelopmental model of schizophrenia.Journal of neural transmission (Vienna, Austria : 1996) · 2026Article
- Why Is Clozapine Uniquely Effective in Treatment-Resistant Schizophrenia? A Review and Proposal.Biological psychiatry · 2026Review
- Glutamate, NAA, and energy metabolism in clinical high risk and first episode psychosis.Scientific reports · 2025Article
- Xanomeline-Trospium for the Treatment of Schizophrenia.Focus (American Psychiatric Publishing) · 2025Review
- Longitudinal changes in striatocortical connectivity in first-episode psychosis associated with the emergence of treatment resistance.Schizophrenia (Heidelberg, Germany) · 2025Article
- Investigating dopaminergic abnormalities in schizophrenia and first-episode psychosis with normative modelling and multisite molecular neuroimaging.Molecular psychiatry · 2025Article
- Radiomic Analysis of Striatal [Molecular imaging and biology · 2025Article
- Single-Subject Network Analysis of FDOPA PET in Parkinson's Disease and Psychosis Spectrum.Human brain mapping · 2025Article
- The hypothesis of biologically based subtypes of schizophrenia: a 10-year update.World psychiatry : official journal of the World Psychiatric Association (WPA) · 2025Article
- Addressing brain metabolic connectivity in treatment-resistant schizophrenia: a novel graph theory-driven application ofSchizophrenia (Heidelberg, Germany) · 2024Article
- How antipsychotics work in schizophrenia: a primer on mechanisms.CNS spectrums · 2024Review
- Dimensional Neuroimaging Endophenotypes: Neurobiological Representations of Disease Heterogeneity Through Machine Learning.Biological psychiatry · 2024Review
- Exploring causal mechanisms of psychosis risk.Neuroscience and biobehavioral reviews · 2024Review
Corrections and comments
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Authors and funding
34 authors at 5 institutions in 2 countries.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.