ArticleThe American journal of psychiatry2016
Pathological Basis for Deficient Excitatory Drive to Cortical Parvalbumin Interneurons in Schizophrenia.
Article in The American journal of psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 3 of them syntheses that pooled it.
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Who cites it
100 citing papers in PubMed, 3 syntheses or guidelines pooled it, 151 citations in OpenAlex.
- Canonical and Non-Canonical Antipsychotics' Dopamine-Related Mechanisms of Present and Next Generation Molecules: A Systematic Review on Translational Highlights for Treatment Response and Treatment-Resistant Schizophrenia.International journal of molecular sciences · 2023Pooled it
- Synapse Pathology in Schizophrenia: A Meta-analysis of Postsynaptic Elements in Postmortem Brain Studies.Schizophrenia bulletin · 2020Pooled it
- Pre-frontal parvalbumin interneurons in schizophrenia: a meta-analysis of post-mortem studies.Journal of neural transmission (Vienna, Austria : 1996) · 2019Pooled it
- Transcriptional Profiles of Somatostatin and Parvalbumin Interneuron Subtypes in the Human Dorsolateral Prefrontal Cortex: Implications for Schizophrenia.The American journal of psychiatry · 2026Article
- Dorsolateral Prefrontal Cortex Circuitry at the Intersection of Cognition and Disease.Biological psychiatry · 2026Review
- Molecular and neural circuit mechanisms of parvalbumin (PV) neurons in depression: Insights and advances.iScience · 2026Review
- Btbd11 regulates glutamatergic synapse organization in GABAergic inhibitory interneurons.bioRxiv : the preprint server for biology · 2026Article
- Prefrontal parvalbumin neurons as a target for enhancing cognition in non-pathological and 22q11.2 microdeletion syndrome mice.Molecular psychiatry · 2026Article
- Disorganized Inhibitory Dynamics in Hippocampal area CA1 of 22q11.2 Deletion Mutant Mice.bioRxiv : the preprint server for biology · 2026Article
- In utero exposure to anti-Caspr2 antibody disrupts parvalbumin interneuron function in the hippocampus.Brain, behavior, and immunity · 2026Article
- Can Sodium Oxybate Mitigate the Symptoms of Schizophrenia?Current neuropharmacology · 2026Review
- A postnatal molecular switch drives activity-dependent maturation of parvalbumin interneurons.Cell · 2025Article
- 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
- Altered Molecular Composition of a Specific Subset of Prefrontal Cortical Excitatory Synapses in Schizophrenia.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Interneuron Loss and Microglia Activation by Transcriptome Analyses in the Basal Ganglia of Tourette Disorder.Biological psychiatry · 2025Article
- Molecular and cellular rhythms in excitatory and inhibitory neurons in the mouse prefrontal cortex.Cerebral cortex (New York, N.Y. : 1991) · 2025Article
- Computational modeling of ketamine-induced changes in gamma-band oscillations: The contribution of parvalbumin and somatostatin interneurons.PLoS computational biology · 2025Article
- KEAP1-NRF2/HO-1 Pathway Promotes Ferroptosis and Neuronal Injury in Schizophrenia.Brain and behavior · 2025Article
- Mean-field analysis of synaptic alterations underlying deficient cortical gamma oscillations in schizophrenia.Journal of computational neuroscience · 2025Article
- Corticolimbic circuitry as a druggable target in schizophrenia spectrum disorders: a narrative review.Translational psychiatry · 2025Review
40 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
objectiveDeficient excitatory drive to parvalbumin-containing cortical interneurons is proposed as a key neural substrate for altered gamma oscillations and cognitive dysfunction in schizophrenia. However, a pathological entity producing such a deficit has not been identified. The authors tested the hypothesis that cortical parvalbumin interneurons receive fewer excitatory synaptic inputs in individuals with schizophrenia.
methodFluorescent immunohistochemistry, confocal microscopy, and post-image processing techniques were used to quantify the number of putative excitatory synapses (i.e., the overlap of vesicular glutamate transporter 1-positive [VGlut1+] puncta and postsynaptic density protein 95-positive [PSD95+] puncta) per surface area of parvalbumin-positive (PV+) or calretinin-positive (CR+) neurons in the dorsolateral prefrontal cortex from schizophrenia subjects and matched unaffected comparison subjects.
resultsMean density of VGlut1+/PSD95+ puncta on PV+ neurons was 18% lower in schizophrenia, a significant difference. This deficit was not influenced by methodological confounds or schizophrenia-associated comorbid factors, not present in monkeys chronically exposed to antipsychotic medications, and not present in CR+ neurons. Mean density of VGlut1+/PSD95+ puncta on PV+ neurons predicted the activity-dependent expression levels of parvalbumin and glutamic acid decarboxylase 67 (GAD67) in schizophrenia subjects but not comparison subjects.
conclusionsTo the authors' knowledge, this is the first demonstration that excitatory synapse density is lower selectively on parvalbumin interneurons in schizophrenia and predicts the activity-dependent down-regulation of parvalbumin and GAD67. Because the activity of parvalbumin interneurons is required for generation of cortical gamma oscillations and working memory function, these findings reveal a novel pathological substrate for cortical dysfunction and cognitive deficits in schizophrenia.
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Registered trials
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