ArticleMolecular psychiatry2020
mGluR5 hypofunction is integral to glutamatergic dysregulation in schizophrenia.
Article in Molecular psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 35 papers, 1 of them a synthesis 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
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Glutamatergic Modulation of Brain Function in Psychosis: A Systematic Review of Neuroimaging Studies.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2025Pooled it
- In vivo mapping of protein-protein interactions of schizophrenia risk factors generates an interconnected disease network.Schizophrenia (Heidelberg, Germany) · 2026Article
- CircHomer1 may contribute to postoperative cognitive impairment by modulating Homer1b/mGluR5-associated signaling in the vCA1 region of aged mice.Frontiers in molecular neuroscience · 2026Article
- Distinct structural deficits in treatment-resistant schizophrenia and their putative neurotransmitter basis: a source-based morphometry analysis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Article
- Psychosis of Epilepsy: An Update on Clinical Classification and Mechanism.Biomolecules · 2025Review
- Article
- Glutamate-Mediated Excitotoxicity in the Pathogenesis and Treatment of Neurodevelopmental and Adult Mental Disorders.International journal of molecular sciences · 2024Review
- Hub genes, a diagnostic model, and immune infiltration based on ferroptosis-linked genes in schizophrenia.IBRO neuroscience reports · 2024Article
- Gamma oscillation plasticity is mediated via parvalbumin interneurons.Science advances · 2024Article
- Homer1 Protects against Retinal Ganglion Cell Pyroptosis by Inhibiting Endoplasmic Reticulum Stress-Associated TXNIP/NLRP3 Inflammasome Activation after Middle Cerebral Artery Occlusion-Induced Retinal Ischemia.International journal of molecular sciences · 2023Article
- A Novel Gliotransmitter, L-β-Aminoisobutyric Acid, Contributes to Pathophysiology of Clinical Efficacies and Adverse Reactions of Clozapine.Biomolecules · 2023Review
- Article
- mGluR5 in amygdala modulates fear memory generalization.Frontiers in behavioral neuroscience · 2023Article
- Glutamatergic dysfunction in Schizophrenia.Translational psychiatry · 2022Review
- Tamalin Function Is Required for the Survival of Neurons and Oligodendrocytes in the CNS.International journal of molecular sciences · 2022Article
- Metabotropic Glutamate Receptors As Emerging Targets for the Treatment of Schizophrenia.Molecular pharmacology · 2022Review
- A postzygotic de novo NCDN mutation identified in a sporadic FTLD patient results in neurochondrin haploinsufficiency and altered FUS granule dynamics.Acta neuropathologica communications · 2022Article
- PTMs: A Missing Piece for Schizophrenia Studies.Advances in experimental medicine and biology · 2022Article
- Different Aberrant Changes of mGluR5 and Its Downstream Signaling Pathways in the Scrapie-Infected Cell Line and the Brains of Scrapie-Infected Experimental Rodents.Frontiers in cell and developmental biology · 2022Article
Corrections and comments
- Retracted
Authors and funding
14 authors at 6 institutions in 1 country.
Funding
Abstract
Multiple lines of evidence point to glutamatergic signaling in the postsynaptic density (PSD) as a pathophysiologic mechanism in schizophrenia. Integral to PSD glutamatergic signaling is reciprocal interplay between GluN and mGluR5 signaling. We examined agonist-induced mGluR5 signaling in the postmortem dorsolateral prefrontal cortex (DLPFC) derived from 17 patients and age-matched and sex-matched controls. The patient group showed a striking reduction in mGluR5 signaling, manifested by decreases in Gq/11 coupling and association with PI3K and Homer compared to controls (p < 0.01 for all). This was accompanied by increases in serine and tyrosine phosphorylation of mGluR5, which can decrease mGluR5 activity via desensitization (p < 0.01). In addition, we find altered protein-protein interaction (PPI) of mGluR5 with RGS4, norbin, Preso 1 and tamalin, which can also attenuate mGluR5 activity. We previously reported molecular underpinnings of GluN hypofunction (decreased GluN2 phosphorylation) and here we show those of reduced mGluR5 signaling in schizophrenia. We find that reduced GluN2 phosphorylation can be precipitated by attenuated mGluR5 activity and that increased mGluR5 phosphorylation can result from decreased GluN function, suggesting a reciprocal interplay between the two pathways in schizophrenia. Interestingly, the patient group showed decreased mGluR5-GluN association (p < 0.01), a mechanistic basis for the reciprocal facilitation. In sum, we present the first direct evidence for mGluR5 hypoactivity, propose a reciprocal interplay between GluN and mGluR5 pathways as integral to glutamatergic dysregulation and suggest protein-protein interactions in mGluR5-GluN complexes as potential targets for intervention in schizophrenia.
Indexed as
Identifiers
What OpenQuestion holds
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.