ReviewNeuropharmacology2012
GABAergic interneuron origin of schizophrenia pathophysiology.
Review in Neuropharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 259 papers, 7 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.
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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.
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Who cites it
259 citing papers in PubMed, 7 syntheses or guidelines pooled it, 491 citations in OpenAlex.
- Altered Expression of GABA-Related Genes in Schizophrenia: Insights from Meta-Analyses of Brain and Blood Samples and iPSC-Derived Organoids.Alpha psychiatry · 2026Pooled it
- Resting-state gamma power in schizophrenia: a systematic review and meta-analysis.Frontiers in psychiatry · 2025Pooled it
- Rational and Translational Implications of D-Amino Acids for Treatment-Resistant Schizophrenia: From Neurobiology to the Clinics.Biomolecules · 2022Pooled it
- Decreased Brain pH as a Shared Endophenotype of Psychiatric Disorders.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Pooled 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
- The impact of Disrupted-in-Schizophrenia 1 (DISC1) on the dopaminergic system: a systematic review.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
- Developmental Brain Network Trajectories Differentiate Resilience and Vulnerability to Psychosis in 22q11.2 Deletion Syndrome.Biological psychiatry global open science · 2026Article
- A ventral hippocampus to nucleus accumbens pathway regulates impulsivity in male but not female rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- A Dual Prediction Error Populations Model of Schizophrenia Spectrum Disorders: Bridging NMDA Hypofunction and Gain Hyperfunction.Schizophrenia bulletin · 2026Article
- Unveiling the enigma of anxiety disorders and depression: from pathogenesis to treatment.Science China. Life sciences · 2026Review
- Transdiagnostic alterations of intrinsic brain activity in major psychiatric disorders.European archives of psychiatry and clinical neuroscience · 2026Article
- The hippocampus as a generative model.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Correlation networks of blood proteins in the neuroimmunology of schizophrenia-replication and extension.Translational psychiatry · 2026Article
- Disorganized Inhibitory Dynamics in Hippocampal area CA1 of 22q11.2 Deletion Mutant Mice.bioRxiv : the preprint server for biology · 2026Article
- Article
- Schizophrenia Pathophysiology: Neurotransmitter Dysfunctions and Biomarker Frontiers.Current topics in medicinal chemistry · 2026Review
- Mapping Neurochemical Signatures onto Brain Structure for Neurotransmitter-Informed Discrimination of Schizophrenia Patients from Healthy Controls.medRxiv : the preprint server for health sciences · 2025Article
- The fundamental disturbance (Grundstörung) of schizophrenia (Part 1): Acquiring a potent endophenotype, exploratory eye movement.PCN reports : psychiatry and clinical neurosciences · 2025Review
- The role of neuroactive steroids in psychiatric and neurological disorders: Neurobiology and therapeutic perspectives.Neuroscience and biobehavioral reviews · 2025Review
199 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
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Hypofunction of N-methyl-d-aspartic acid-type glutamate receptors (NMDAR) induced by the systemic administration of NMDAR antagonists is well known to cause schizophrenia-like symptoms in otherwise healthy subjects. However, the brain areas or cell-types responsible for the emergence of these symptoms following NMDAR hypofunction remain largely unknown. One possibility, the so-called "GABAergic origin hypothesis," is that NMDAR hypofunction at GABAergic interneurons, in particular, is sufficient for schizophrenia-like effects. In one attempt to address this issue, transgenic mice were generated in which NMDARs were selectively deleted from cortical and hippocampal GABAergic interneurons, a majority of which were parvalbumin (PV)-positive. This manipulation triggered a constellation of phenotypes--from molecular and physiological to behavioral--resembling characteristics of human schizophrenia. Based on these results, and in conjunction with previous literature, we argue that during development, NMDAR hypofunction at cortical, PV-positive, fast-spiking interneurons produces schizophrenia-like effects. This review summarizes the data demonstrating that in schizophrenia, GABAergic (particularly PV-positive) interneurons are disrupted. PV-positive interneurons, many of which display a fast-spiking firing pattern, are critical not only for tight temporal control of cortical inhibition but also for the generation of synchronous membrane-potential gamma-band oscillations. We therefore suggest that in schizophrenia the specific ability of fast-spiking interneurons to control and synchronize disparate cortical circuits is disrupted and that this disruption may underlie many of the schizophrenia symptoms. We further argue that the high vulnerability of corticolimbic fast-spiking interneurons to genetic predispositions and to early environmental insults--including excitotoxicity and oxidative stress--might help to explain their significant contribution to the development of 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.