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Tytuł:
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Glutamate in the Dorsolateral Prefrontal Cortex in Patients With Schizophrenia: A Meta-analysis of H-Magnetic Resonance Spectroscopy Studies.
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Autorzy:
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Kaminski J; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Psychiatry and Psychotherapy CCM, Berlin, Germany; Berlin Institute of Health, Berlin, Germany. Electronic address: .
Mascarell-Maricic L; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Psychiatry and Psychotherapy CCM, Berlin, Germany.
Fukuda Y; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Psychiatry and Psychotherapy CCM, Berlin, Germany.
Katthagen T; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Psychiatry and Psychotherapy CCM, Berlin, Germany.
Heinz A; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Psychiatry and Psychotherapy CCM, Berlin, Germany; Bernstein Center for Computational Neuroscience, Berlin, Germany.
Schlagenhauf F; Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Psychiatry and Psychotherapy CCM, Berlin, Germany; Berlin Institute of Health, Berlin, Germany; Bernstein Center for Computational Neuroscience, Berlin, Germany; Department of Neurology, Max Planck Institute for Human Cognitive and Brain Science, Leipzig, Germany.
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Źródło:
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Biological psychiatry [Biol Psychiatry] 2021 Feb 01; Vol. 89 (3), pp. 270-277. Date of Electronic Publication: 2020 Sep 08.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: New York, NY : Elsevier
Original Publication: New York, Plenum Pub. Corp.
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MeSH Terms:
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Glutamic Acid*
Schizophrenia*/diagnostic imaging
Schizophrenia*/drug therapy
Glutamine ; Humans ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Prefrontal Cortex/diagnostic imaging ; Proton Magnetic Resonance Spectroscopy
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Contributed Indexing:
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Keywords: (1)H-MRS; Antipsychotic medication; Dorsolateral prefrontal cortex; Glutamate; Psychosis; Schizophrenia
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Substance Nomenclature:
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0RH81L854J (Glutamine)
3KX376GY7L (Glutamic Acid)
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Entry Date(s):
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Date Created: 20201101 Date Completed: 20210423 Latest Revision: 20210423
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Update Code:
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20240105
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DOI:
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10.1016/j.biopsych.2020.09.001
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PMID:
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33129486
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Background: To date, there is no systematic overview of glutamate in the dorsolateral prefrontal cortex (DLPFC) of patients with schizophrenia. Here, we meta-analyzed case-control studies of high-field proton magnetic resonance spectroscopy ( 1 H-MRS) investigating glutamate in DLPFC. Additionally, we estimated variance ratios to investigate homo/heterogeneity.
Methods: Preregistration of the study was performed on September 20, 2019. The predefined literature search on PubMed comprised articles with search terms (magnetic resonance spectroscopy OR MRS) AND (glutamate OR glut∗ OR GLX) AND (schizophrenia OR psychosis OR schizophren∗). Meta-analyses with a fixed- and random-effects model with inverse variance method, DerSimonian-Laird estimator for τ 2 , and Cohen's d were calculated. For differences in variability, we calculated a random-effects model for measures of variance ratios. The primary study outcome was the difference in glutamate in the DLPFC in cases versus controls. Secondary outcomes were differences in variability.
Results: The quantitative analysis comprised 429 cases and 365 controls. Overall, we found no group difference (d = 0.03 [95% confidence interval (CI), -0.20 to 0.26], z = 0.28, p = .78). Sensitivity analysis revealed an effect for medication status (Q = 8.35, p = .039), i.e., increased glutamate in antipsychotic-naïve patients (d = 0.46 [95% CI, 0.08 to 0.84], z = 2.37, p = .018). Concerning variance ratios, we found an effect of medication status (Q = 16.95, p < .001) due to lower coefficient of variation ratio (CVR) in medication-naïve patients (logCVR = -0.49 [95% CI, -0.78 to -0.20], z = -3.33, p < .001). In studies with medicated patients, we found higher CVR (logCVR = 0.22 [95% CI, 0.06 to 0.39], z = 2.67; p = .008).
Conclusions: We carefully interpret the higher levels and lower variability in cortical glutamate in antipsychotic-naïve patients as a possible key factor resulting from a putative allostatic mechanism. We conclude that care has to be taken when evaluating metabolite levels in clinical samples in which medication might confound findings.
(Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)
Comment in: Biol Psychiatry. 2021 Feb 1;89(3):e1-e3. (PMID: 33357632)
