ArticleThe American journal of psychiatry2011
Cortical deficits of glutamic acid decarboxylase 67 expression in schizophrenia: clinical, protein, and cell type-specific features.
Article in The American journal of psychiatry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 178 papers, 2 of them syntheses that pooled it.
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Who cites it
178 citing papers in PubMed, 2 syntheses or guidelines pooled it, 281 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
- Cortical control of chandelier cells in neural codes.Frontiers in cellular neuroscience · 2022Pooled it
- Memantine Effects on Electroencephalographic Measures of Putative Excitatory/Inhibitory Balance in Schizophrenia.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2020Trial
- Perinatal choline effects on neonatal pathophysiology related to later schizophrenia risk.The American journal of psychiatry · 2013Trial
- Vagal sensing of altered gut microbiota links to externalizing behaviors.Gut microbes · 2026Article
- The Potential of Cannabidiol for the Treatment of Psychosis: Endocannabinoid Regulation of Serotonergic Neurotransmission via Serotonin 5-HT1A/2A Receptors.Neurochemical research · 2026Review
- Schizophrenia: from mechanism to therapy.Science China. Life sciences · 2026Review
- Linking reduced prefrontal microcircuit inhibition in schizophrenia to EEG biomarkers in silico.PLoS computational biology · 2026Article
- Oral Supplementation With a Bovine Thymus Extract Reduces Neuronal Excitability in Aging Mice.FASEB bioAdvances · 2026Article
- Article
- Unraveling the mysteries of schizophrenia: Insights into prefrontal cortex dysfunction and therapeutic implications.World journal of psychiatry · 2025Review
- Excitation/inhibition imbalance and conversion to psychosis in the clinical high risk syndrome: Biophysical modeling finds reduced pyramidal cell excitability across EEG paradigms.medRxiv : the preprint server for health sciences · 2025Article
- Aging disrupts the coordination between mRNA and protein expression in mouse and human midbrain.Molecular psychiatry · 2025Article
- Targeting the Roots of Psychosis: The Role of Aberrant Salience.Pediatric reports · 2025Review
- Metabolic syndrome in patients with schizophrenia: Underlying mechanisms and therapeutic approaches (Review).Molecular medicine reports · 2025Review
- Mean-field analysis of synaptic alterations underlying deficient cortical gamma oscillations in schizophrenia.Journal of computational neuroscience · 2025Article
- Reduced temporal variability of cortical excitation/inhibition ratio in schizophrenia.Schizophrenia (Heidelberg, Germany) · 2025Article
- Disturbance of neurotransmitter metabolites in peripheral blood of schizophrenia patients treated with olanzapine: a preliminary targeted metabolomic study.BMC psychiatry · 2025Article
- Psychosis of Epilepsy: An Update on Clinical Classification and Mechanism.Biomolecules · 2025Review
- Inhibitory Systems in Brain Evolution: Pathways of Vulnerability in Neurodevelopmental Disorders.Brain, behavior and evolution · 2025Review
118 more citing papers are in PubMed but not listed here.
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7 authors at 1 institution in 1 country.
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Abstract
objectiveCognitive deficits in schizophrenia are associated with altered activity of the dorsolateral prefrontal cortex, which has been attributed to lower expression of the 67 kDa isoform of glutamic acid decarboxylase (GAD67), the major γ-aminobutyric acid (GABA)-synthesizing enzyme. However, little is known about the relationship of prefrontal GAD67 mRNA levels and illness severity, translation of the transcript into protein, and protein levels in axon terminals, the key site of GABA production and function.
methodQuantitative polymerase chain reaction was used to measure GAD67 mRNA levels in postmortem specimens of dorsolateral prefrontal cortex from subjects with schizophrenia and matched comparison subjects with no known history of psychiatric or neurological disorders (N=42 pairs). In a subset of this cohort in which potential confounds of protein measures were controlled (N=19 pairs), Western blotting was used to quantify tissue levels of GAD67 protein in tissue. In five of these pairs, multilabel confocal immunofluorescence was used to quantify GAD67 protein levels in the axon terminals of parvalbumin-containing GABA neurons, which are known to have low levels of GAD67 mRNA in schizophrenia.
resultsGAD67 mRNA levels were significantly lower in schizophrenia subjects (by 15%), but transcript levels were not associated with predictors or measures of illness severity or chronicity. In schizophrenia subjects, GAD67 protein levels were significantly lower in total gray matter (by 10%) and in parvalbumin axon terminals (by 49%).
conclusionsThe findings that lower GAD67 mRNA expression is common in schizophrenia, that it is not a consequence of having the illness, and that it leads to less translation of the protein, especially in the axon terminals of parvalbumin-containing neurons, support the hypothesis that lower GABA synthesis in parvalbumin neurons contributes to dorsolateral prefrontal cortex dysfunction and impaired cognition in schizophrenia.
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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.