ArticleMolecular psychiatry2015
Magnetic resonance spectroscopy and tissue protein concentrations together suggest lower glutamate signaling in dentate gyrus in schizophrenia.
Article in Molecular psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 4 of them syntheses that pooled it.
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Who cites it
47 citing papers in PubMed, 4 syntheses or guidelines pooled it, 80 citations in OpenAlex.
- Glutamatergic and GABAergic metabolite levels in schizophrenia-spectrum disorders: a meta-analysis ofMolecular psychiatry · 2022Pooled it
- Medial Prefrontal Cortex Glutamate Is Reduced in Schizophrenia and Moderated by Measurement Quality: A Meta-analysis of Proton Magnetic Resonance Spectroscopy Studies.Biological psychiatry · 2021Pooled it
- Neuroimaging studies of GABA in schizophrenia: a systematic review with meta-analysis.Translational psychiatry · 2017Pooled it
- Brain GABA levels across psychiatric disorders: A systematic literature review and meta-analysis of (1) H-MRS studies.Human brain mapping · 2016Pooled it
- Modulation of hippocampal activity in schizophrenia with levetiracetam: a randomized, double-blind, cross-over, placebo-controlled trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Trial
- A randomized, double-blind, placebo-controlled trial of lamotrigine for prescription corticosteroid effects on the human hippocampus.European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology · 2019Trial
- In vivo brain macromolecules in schizophrenia spectrum disorders.Schizophrenia (Heidelberg, Germany) · 2026Article
- Aging in Schizophrenia: Perspectives on Molecular Mechanisms and a Mini-review.Schizophrenia bulletin · 2026Review
- Review
- Neurochemical changes in GABA+, Glx, and the excitatory/inhibitory ratio in the calcarine cortex with healthy aging.NeuroImage · 2025Article
- Pharmacological reduction of reverse-translated hippocampal hyperactivity in mouse: relevance for psychosis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Basal glutamate in the hippocampus and the dorsolateral prefrontal cortex in schizophrenia: Relationships to cognitive proficiency investigated with structural equation modelling.The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry · 2023Article
- Erbb4 Deletion From Inhibitory Interneurons Causes Psychosis-Relevant Neuroimaging Phenotypes.Schizophrenia bulletin · 2023Article
- Hippocampal circuit dysfunction in psychosis.Translational psychiatry · 2022Review
- Gut Microbiome: A Brief Review on Its Role in Schizophrenia and First Episode of Psychosis.Microorganisms · 2022Review
- The schizophrenia and gut microbiota: A bibliometric and visual analysis.Frontiers in psychiatry · 2022Article
- Mnemonic Discrimination Deficits in First-Episode Psychosis and a Ketamine Model Suggest Dentate Gyrus Pathology Linked to NMDA Receptor Hypofunction.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2021Article
- Gut microbial biomarkers for the treatment response in first-episode, drug-naïve schizophrenia: a 24-week follow-up study.Translational psychiatry · 2021Article
- Machine learning reveals bilateral distribution of somatic L1 insertions in human neurons and glia.Nature neuroscience · 2021Article
- Abnormalities in the copper transporter CTR1 in postmortem hippocampus in schizophrenia: A subregion and laminar analysis.Schizophrenia research · 2021Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hippocampal dysfunction in schizophrenia is widely acknowledged, yet the mechanism of such dysfunction remains debated. In this study we investigate the excitatory and inhibitory hippocampal neurotransmission using two complementary methodologies, proton magnetic resonance spectroscopy (MRS) and tissue biochemistry, sampling individuals with schizophrenia in vivo and postmortem hippocampal tissue in vitro. The results show significantly lower glutamate concentrations in hippocampus in schizophrenia, an in vivo finding mirrored by lower GluN1 protein levels selectively in the dentate gyrus (DG) in vitro. In a mouse model with a DG knockout of the GRIN1 gene, we further confirmed that a selective decrease in DG GluN1 is sufficient to decrease the glutamate concentrations in the whole hippocampus. Gamma-aminobutyric acid (GABA) concentrations and GAD67 protein were not significantly different in hippocampus in schizophrenia. Similarly, GABA concentrations in the hippocampi of mice with a DG knockout of the GRIN1 gene were not significantly different from wild type. These findings provide strong evidence implicating the excitatory system within hippocampus in the pathophysiology of schizophrenia, particularly indicating the DG as a site of pathology.
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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.