ReviewHandbook of experimental pharmacology2012
Glutamatergic synaptic dysregulation in schizophrenia: therapeutic implications.
Review in Handbook of experimental pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
86 citing papers in PubMed, 179 citations in OpenAlex.
- Trial
- Article
- Glycine-modulating Slc6a20a-ASO restores NMDA receptor function in SHANK2 and SHANK3-mutant mice and cortical organoids.Nature communications · 2026Article
- Chronic Co-administration of Methylphenidate and Fluoxetine Reduces Striatal NMDA Receptor Binding in Adolescent Rats.Neurochemical research · 2026Article
- Machine learning-based morphological brain analysis in schizophrenia and unaffected siblings: a multisite study of potential risk markers.Frontiers in neuroscience · 2026Article
- Functional Analysis of Antipsychotics in Human iPSC-Based Neural Progenitor 2D and 3D Schizophrenia Models.International journal of molecular sciences · 2025Article
- miRNA-Based Diagnosis of Schizophrenia Using Machine Learning.International journal of molecular sciences · 2025Article
- mGluR5 positive allosteric modulation prevents MK-801 induced increases in extracellular glutamate in the rat medial prefrontal cortex.Neuroscience · 2024Article
- Eosinophils and Cognitive Impairment in Schizophrenia: A New Perspective.Journal of blood medicine · 2024Review
- Article
- Developmental Manipulation-Induced Changes in Cognitive Functioning.Current topics in behavioral neurosciences · 2023Article
- Pregestational Exposure toCells · 2022Article
- Differential Effects of Chronic Methamphetamine Treatment on High-Frequency Oscillations and Responses to Acute Methamphetamine and NMDA Receptor Blockade in Conscious Mice.Brain sciences · 2022Article
- A role for endothelial NMDA receptors in the pathophysiology of schizophrenia.Schizophrenia research · 2022Review
- Managing electromyogram contamination in scalp recordings: An approach identifying reliable beta and gamma EEG features of psychoses or other disorders.Brain and behavior · 2022Article
- DHF-7 Ameliorates Behavioral Disorders and White Matter Lesions by Regulating BDNF and Fyn in a Mouse Model of Schizophrenia Induced by Cuprizone and MK-801.The international journal of neuropsychopharmacology · 2022Article
- Receptor-Mediated AKT/PI3K Signalling and Behavioural Alterations in Zebrafish Larvae Reveal Association between Schizophrenia and Opioid Use Disorder.International journal of molecular sciences · 2022Article
- Drug Design Targeting the Muscarinic Receptors and the Implications in Central Nervous System Disorders.Biomedicines · 2022Review
- Ulotaront: A TAAR1 Agonist for the Treatment of Schizophrenia.ACS medicinal chemistry letters · 2022Article
- The interplay between glutamatergic circuits and oxytocin neurons in the hypothalamus and its relevance to neurodevelopmental disorders.Journal of neuroendocrinology · 2021Review
26 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
5 authors at 2 institutions in 1 country.
Funding
Abstract
Schizophrenia affects approximately 1% of the population and continues to be associated with poor outcome because of the limited efficacy of and noncompliance with existing antipsychotic medications. An alternative hypothesis invoking the excitatory neurotransmitter, glutamate, arose out of clinical observations that NMDA receptor antagonists, the dissociative anesthetics like ketamine, can replicate in normal individuals the full range of symptoms of schizophrenia including psychosis, negative symptoms, and cognitive impairments. Low dose ketamine can also re-create a number of physiologic abnormalities characteristic of schizophrenia. Postmortem studies have revealed abnormalities in endogenous modulators of NMDA receptors in schizophrenia as well as components of a postsynaptic density where NMDA receptors are localized. Gene association studies have revealed several genes that affect NMDA receptor function whose allelic variants are associated with increased risk for schizophrenia including genes encoding D-amino acid oxidase, its modulator G72, dysbindin, and neuregulin. The parvalbumin-positive, fast-firing GABAergic interneurons that provide recurrent inhibition to cortical-limbic pyramidal neurons seem to be most sensitive to NMDA receptor hypofunction. As a consequence, disinhibition of glutamatergic efferents disrupts cortical processing, causing cognitive impairments and negative symptoms, and drives subcortical dopamine release, resulting in psychosis. Drugs designed to correct the cortical-limbic dysregulated glutamatergic neurotransmission show promise for reducing negative and cognitive symptoms of schizophrenia as well as its positive symptoms.
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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.