ReviewAnnals of the New York Academy of Sciences2015
The glutamate hypothesis of schizophrenia: evidence from human brain tissue studies.
Review in Annals of the New York Academy of Sciences, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers, 5 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
145 citing papers in PubMed, 5 syntheses or guidelines pooled it, 265 citations in OpenAlex.
- Glutamatergic Modulation of Brain Function in Psychosis: A Systematic Review of Neuroimaging Studies.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2025Pooled it
- The impact of sex on gene expression in the brain of schizophrenic patients: a systematic review and meta-analysis of transcriptomic studies.Biology of sex differences · 2024Pooled it
- Pooled it
- A meta-analysis of ultra-high field glutamate, glutamine, GABA and glutathione 1HMRS in psychosis: Implications for studies of psychosis risk.Schizophrenia research · 2020Pooled it
- A systematic meta-analysis of the association of Neuregulin 1 (NRG1), D-amino acid oxidase (DAO), and DAO activator (DAOA)/G72 polymorphisms with schizophrenia.Journal of neural transmission (Vienna, Austria : 1996) · 2018Pooled it
- Exercise as a protective mechanism against the negative effects of oxidative stress in first-episode psychosis: a biomarker-led study.Translational psychiatry · 2020Trial
- Cannabis use and glutamate across the psychosis spectrum: in vivo evidence from 7T proton magnetic resonance spectroscopy.Molecular psychiatry · 2026Article
- Glutamatergic Modulators in Schizophrenia: Are We Ready to Move Beyond the Narrow Focus on Dopamine? A Potential Paradigm Shift in Psychopharmacology.Alpha psychiatry · 2026Article
- Myo-inositol concentration in the medial prefrontal cortex is associated with changes in brain white matter microstructure in early psychosis.Translational psychiatry · 2026Article
- Targeting endoplasmic reticulum stress and protein misfolding in schizophrenia: the emerging promise of sigma-1 receptor agonists.Psychopharmacology · 2026Review
- GlyT1 (SLC6A9) inhibition in neurological and psychiatric disorders.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- The association among glutamate, GABA, and anterior cingulate connectivity in schizophrenia spectrum disorders: Implications for symptom domains.European psychiatry : the journal of the Association of European Psychiatrists · 2026Article
- Modulation of glycine transporters as a novel therapeutic strategy in neuropsychiatry.Psychopharmacology · 2026Review
- Differential DNA-methylation of synaptic genes in CSF and blood in schizophrenia.Schizophrenia (Heidelberg, Germany) · 2026Article
- Nutritional Management of Schizophrenia: Gut-Brain Axis Mechanisms and Dietary Interventions.Molecular neurobiology · 2026Review
- MiR-7 in neurological disorders: beyond metabolic dysregulation.Frontiers in neuroscience · 2026Review
- Spatially resolved translational dysregulation inbioRxiv : the preprint server for biology · 2025Article
- Cannabis Use and Glutamate across the Psychosis Spectrum: In Vivo Evidence from 7T Proton Magnetic Resonance Spectroscopy.Research square · 2025Article
- Blood‑brain barrier dysfunction in schizophrenia: Mechanisms and implications (Review).International journal of molecular medicine · 2025Review
- The myth of the Bayesian brain.European journal of applied physiology · 2025Review
85 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
4 authors at 3 institutions in 1 country.
Funding
Abstract
A number of studies have indicated that antagonists of the N-methyl-d-aspartate subtypes of glutamate receptors can cause schizophrenia-like symptoms in healthy individuals and exacerbate symptoms in individuals with schizophrenia. These findings have led to the glutamate hypothesis of schizophrenia. Here we review the evidence for this hypothesis in postmortem studies of brain tissue from individuals affected by schizophrenia, summarizing studies of glutamate neuron morphology, of expression of glutamate receptors and transporters, and of the synthesizing and metabolizing enzymes for glutamate and its co-agonists. We found consistent evidence of morphological alterations of dendrites of glutamatergic neurons in the cerebral cortex of subjects with schizophrenia and of reduced levels of the axon bouton marker synaptophysin. There were no consistent alterations of mRNA expression of glutamate receptors, although there has been limited study of the corresponding proteins. Studies of the glutamate metabolic pathway have been limited, although there is some evidence that excitatory amino acid transporter-2, glutamine synthetase, and glutaminase have altered expression in schizophrenia. Future studies would benefit from additional direct examination of glutamatergic proteins. Further advances, such as selective testing of synaptic microdomains, cortical layers, and neuronal subtypes, may also be required to elucidate the nature of glutamate signaling impairments in schizophrenia.
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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.