SynthesisMolecular psychiatry2022
Glutamatergic and GABAergic metabolite levels in schizophrenia-spectrum disorders: a meta-analysis of
Synthesis in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07196423 (Glutamate Changes as a New Neurocognitive Marker in Psychosis), which is not on this map. Cited by 98 papers, 11 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.
Glutamate Changes as a New Neurocognitive Marker in Psychosis
Who cites it
98 citing papers in PubMed, 11 syntheses or guidelines pooled it, 156 citations in OpenAlex.
- Multimodal microglial and kynurenine pathway alterations across the affective-psychosis spectrum: a systematic review of patterns, heterogeneity, and dimensional implications.Molecular psychiatry · 2026Pooled it
- A systematic review and meta-analysis of the auditory steady-state response in schizophrenia, bipolar disorder, and autism spectrum disorder.Molecular psychiatry · 2026Pooled it
- Non-Clozapine interventions in treatment-resistant schizophrenia: a systematic review and meta-analysis.Molecular psychiatry · 2026Pooled it
- Glutamatergic Modulation of Brain Function in Psychosis: A Systematic Review of Neuroimaging Studies.Biological psychiatry. Cognitive neuroscience and neuroimaging · 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
- Insulin effects on core neurotransmitter pathways involved in schizophrenia neurobiology: a meta-analysis of preclinical studies. Implications for the treatment.Molecular psychiatry · 2023Pooled it
- Variability and magnitude of brain glutamate levels in schizophrenia: a meta and mega-analysis.Molecular psychiatry · 2023Pooled it
- Canonical and Non-Canonical Antipsychotics' Dopamine-Related Mechanisms of Present and Next Generation Molecules: A Systematic Review on Translational Highlights for Treatment Response and Treatment-Resistant Schizophrenia.International journal of molecular sciences · 2023Pooled it
- Medial Frontal Cortex GABA Concentrations in Psychosis Spectrum and Mood Disorders: A Meta-analysis of Proton Magnetic Resonance Spectroscopy Studies.Biological 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
- Functional MRS studies of GABA and glutamate/Glx - A systematic review and meta-analysis.Neuroscience and biobehavioral reviews · 2023Pooled it
- Diazepam modulates anterior cingulate glutamate levels in people at clinical high-risk for psychosis.The international journal of neuropsychopharmacology · 2026Trial
- Efficacy of Cortical-Hippocampal Target Intermittent Theta Burst Stimulation (iTBS) on Associative Memory of Schizophrenia: A Double-Blind, Randomized Sham-Controlled Trial.Neuropsychiatric disease and treatment · 2024Trial
- Astrocytic connexin 43 hemichannel dysregulation drives prefrontal circuit dysfunction and schizophrenia-like behaviors.Molecular psychiatry · 2026Article
- Unsupervised Clustering of ACC and Hippocampal Metabolites Identifies Subgroups in Antipsychotic-Naïve First-Episode Psychosis.Schizophrenia bulletin · 2026Article
- 7T magnetic resonance spectroscopic imaging of subcortical neurometabolites across antipsychotic treatment in acutely symptomatic early-phase schizophrenia spectrum disorders.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Local chemoarchitecture explains widespread lower cortical thickness associated with clinical high risk for psychosis.Molecular psychiatry · 2026Article
- Schizophrenia: from mechanism to therapy.Science China. Life sciences · 2026Review
- Schizophrenia and disordered sensorimotor control: challenges, mechanisms and opportunities.Brain : a journal of neurology · 2026Review
- Group Differences of Multiregion Glutamate Concentration in Clinical High Risk and Schizophrenia.The European journal of neuroscience · 2026Article
38 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundThe glutamate (Glu) and gamma aminobutyric acid (GABA) hypotheses of schizophrenia were proposed in the 1980s. However, current findings on those metabolite levels in schizophrenia have been inconsistent, and the relationship between their abnormalities and the pathophysiology of schizophrenia remains unclear. To summarize the nature of the alterations of glutamatergic and GABAergic systems in schizophrenia, we conducted meta-analyses of proton magnetic resonance spectroscopy (
methodsA systematic literature search was conducted using Embase, Medline, PsycINFO, and PubMed. Original studies that compared four metabolite levels (Glu, glutamine [Gln], Glx [Glu+Gln], and GABA), as measured by
resultsOne-hundred-thirty-four studies met the eligibility criteria, totaling 7993 participants with SZ-spectrum disorders and 8744 HC. 14 out of 18 ROIs had enough numbers of studies to examine the group difference in the metabolite levels. In the whole group, Glx levels in the basal ganglia (g = 0.32; 95% CIs: 0.18-0.45) were elevated. Subgroup analyses showed elevated Glx levels in the hippocampus (g = 0.47; 95% CIs: 0.21-0.73) and dorsolateral prefrontal cortex (g = 0.25; 95% CIs: 0.05-0.44) in unmedicated patients than HC. GABA levels in the MCC were decreased in the first-episode psychosis group compared with HC (g = -0.40; 95% CIs: -0.62 to -0.17). Treatment-resistant schizophrenia (TRS) group had elevated Glx and Glu levels in the MCC (Glx: g = 0.7; 95% CIs: 0.38-1.01; Glu: g = 0.63; 95% CIs: 0.31-0.94) while MCC Glu levels were decreased in the patient group except TRS (g = -0.17; 95% CIs: -0.33 to -0.01).
conclusionsIncreased glutamatergic metabolite levels and reduced GABA levels indicate that the disruption of excitatory/inhibitory balance may be related to the pathophysiology of schizophrenia-spectrum disorders.
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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.