SynthesisBiological psychiatry2021
Medial Prefrontal Cortex Glutamate Is Reduced in Schizophrenia and Moderated by Measurement Quality: A Meta-analysis of Proton Magnetic Resonance Spectroscopy Studies.
Synthesis in Biological psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 7 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
34 citing papers in PubMed, 7 syntheses or guidelines pooled it, 49 citations in OpenAlex.
- Transdiagnostic reduction in cortical choline-containing compounds in anxiety disorders: aMolecular psychiatry · 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
- Greater Choline-Containing Compounds and Myo-inositol in Treatment-Resistant Versus Responsive Schizophrenia: ABiological psychiatry. Cognitive neuroscience and neuroimaging · 2024Pooled it
- Spectroscopic meta-analyses reveal novel metabolite profiles across methamphetamine and cocaine substance use disorder.Drug and alcohol dependence · 2023Pooled it
- Variability and magnitude of brain glutamate levels in schizophrenia: a meta and mega-analysis.Molecular psychiatry · 2023Pooled it
- Meta-analytic evidence of elevated choline, reduced N-acetylaspartate, and normal creatine in schizophrenia and their moderation by measurement quality, echo time, and medication status.NeuroImage. Clinical · 2023Pooled it
- Brain metabolite alterations related to alcohol use: a meta-analysis of proton magnetic resonance spectroscopy studies.Molecular psychiatry · 2022Pooled it
- The Molecular Machinery of Synaptic Plasticity and Its Potential Role in the Aetiology of Schizophrenia.Molecular neurobiology · 2026Review
- Group Differences of Multiregion Glutamate Concentration in Clinical High Risk and Schizophrenia.The European journal of neuroscience · 2026Article
- Interrelations between dopaminergic-, gabaergic- and glutamatergic neurotransmitters in antipsychotic-naïve psychosis patients and the association to initial treatment response.Molecular psychiatry · 2026Article
- The link between GABA levels and P300 abnormalities in schizophrenia spectrum disorders: regional and symptom-based insights.Schizophrenia (Heidelberg, Germany) · 2026Article
- Cerebral glutamate levels over two years in initially antipsychotic-naïve first-episode patients with psychosis are related to clinical symptoms and cognition.Molecular psychiatry · 2025Article
- Glutamate, Contextual Insensitivity, and Disorganized Speech in First-Episode Schizophrenia: A 7T Magnetic Resonance Spectroscopy Study.Biological psychiatry global open science · 2025Article
- Changes in glutamate levels in anterior cingulate cortex following 16 weeks of antipsychotic treatment in antipsychotic-naïve first-episode psychosis patients.Psychological medicine · 2025Article
- Corticolimbic circuitry as a druggable target in schizophrenia spectrum disorders: a narrative review.Translational psychiatry · 2025Review
- Statistical non-independence of brain metabolite concentrations whether normalized to creatine or water.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2025Article
- Altered brain metabolites in male nonhuman primate offspring exposed to maternal immune activation.Brain, behavior, and immunity · 2024Article
- Prefrontal metabolite alterations in individuals with posttraumatic stress disorder: a 7T magnetic resonance spectroscopy study.bioRxiv : the preprint server for biology · 2024Article
- The Role of microRNA in Schizophrenia: A Scoping Review.International journal of molecular sciences · 2024Article
- Magnetic Resonance Spectroscopy Studies of Brain Energy Metabolism in Schizophrenia: Progression from Prodrome to Chronic Psychosis.Current psychiatry reports · 2023Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMagnetic resonance spectroscopy studies measuring brain glutamate separately from glutamine are helping elucidate schizophrenia pathophysiology. An expanded literature and improved methodologies motivate an updated meta-analysis examining effects of measurement quality and other moderating factors in characterizing abnormal glutamate levels in schizophrenia.
methodsSearching previous meta-analyses and the MEDLINE database identified 83 proton magnetic resonance spectroscopy datasets published through March 25, 2020. Three quality metrics were extracted-Cramér-Rao lower bound (CRLB), line width, and coefficient of variation. Pooled effect sizes (Hedges' g) were calculated with random-effects, inverse variance-weighted models. Moderator analyses were conducted using quality metrics, field strength, echo time, medication, age, and stage of illness.
resultsAcross 36 datasets (2086 participants), medial prefrontal cortex glutamate was significantly reduced in patients (g = -0.19, confidence interval [CI] = -0.07 to -0.32). CRLB and coefficient of variation quality subgroups significantly moderated this effect. Glutamate was significantly more reduced in studies with lower CRLB or coefficient of variation (g = -0.44, CI = -0.29 to -0.60, and g = -0.43, CI = -0.29 to -0.57, respectively). Studies using echo time ≤20 ms also showed significantly greater reduction in glutamate (g = -0.41, CI = -0.26 to -0.55). Across 11 hippocampal datasets, group differences and moderator effects were nonsignificant. Group effects in thalamus and dorsolateral prefrontal cortex were also nonsignificant.
conclusionsHigh-quality measurements reveal consistently reduced medial prefrontal cortex glutamate in schizophrenia. Stricter CRLB criteria and reduced nuisance variance may increase the sensitivity of future studies examining additional regions and the pathophysiological significance of abnormal glutamate levels in schizophrenia.
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