The DOI matches its Crossref record; 120 of the 123 references it cites were found in a registry or an index.
Cortical inhibitory neurons and schizophrenia
Abstract
Impairments in certain cognitive functions, such as working memory, are core features of schizophrenia. Convergent findings indicate that a deficiency in signalling through the TrkB neurotrophin receptor leads to reduced GABA (gamma-aminobutyric acid) synthesis in the parvalbumin-containing subpopulation of inhibitory GABA neurons in the dorsolateral prefrontal cortex of individuals with schizophrenia. Despite both pre- and postsynaptic compensatory responses, the resulting alteration in perisomatic inhibition of pyramidal neurons contributes to a diminished capacity for the gamma-frequency synchronized neuronal activity that is required for working memory function. These findings reveal specific targets for therapeutic interventions to improve cognitive function in individuals with schizophrenia.
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In the citing paper
“Reduced expression of GAD67, the main GABA-synthesizing enzyme in the brain, appears to contribute to altered interneuron activity in psychosis [86,87] .”
From The traumagenic neurodevelopmental model of psychosis revisited (2014) · cites this paper as [86]
In the citing paper
“Certain classes of GABA interneurons are altered in individuals with psychosis, in particular reduced density in the anterior cingulate and reduced activity in the dorsolateral prefrontal cortex in the subpopulation expressing parvalbumin [84-86] .”
From The traumagenic neurodevelopmental model of psychosis revisited (2014) · cites this paper as [86]
In the citing paper
“Thus, the correct balance of inhibition and excitation seems to be critical for normative executive function, and conversely, disturbance of this balance is thought to be a fundamental component of psychiatric illness.69, 70”
From A role for synaptic plasticity in the adolescent development of executive function (2013) · cites this paper as [69]
In the citing paper
“Moreover, the expression of several GABA receptors and markers of inhibitory synapses are also altered in schizophrenia 50 .”
From Developmental timing and critical windows for the treatment of psychiatric disorders (2016) · cites this paper as [50]
In the citing paper
“Schizophrenia is increasingly recognized as a neurodevelopmental disorder that involves alterations in brain circuits, including dysfunction of parvalbumin (PV)-positive, fast-spiking GABA neurons (1, 2).”
From Prolonged Period of Cortical Plasticity upon Redox Dysregulation in Fast-Spiking Interneurons (2015) · cites this paper as [1]
In the citing paper
“its onset is linked to a potential disruption of the physiological maturation of inhibitory neural networks consisting of fast-spiking parvalbumin-positive gamma-aminobutric acid (GABAergic) interneurons”
From Perineuronal nets and schizophrenia: The importance of neuronal coatings (2014) · cites this paper as Lewis et al., 2005
In the citing paper
“Dysfunction and/or deficient inhibitory output from PV interneurons may be a common mechanism of multiple psychiatric disorders, such as schizophrenia (SCZ) (Lewis et al. 2005), autism spectrum disorders (ASD) (Gao and Penzes 2015) and bipolar disorder (BD) (Ruden et al. 2021).”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Lewis et al. 2005
In the citing paper
“Specifically, there is growing support for a hypothesis that cortical disinhibition occurs in schizophrenia, due to the disrupted functioning of inhibitory interneurons, which results in elevated E/I ratio (Lewis et al. 2005;Marin 2012).”
From Linking microcircuit dysfunction to cognitive impairment: Effects of disinhibition associated with schizophrenia in a cortical working memory model (2014) · cites this paper as Lewis et al. 2005
In the citing paper
“The prefrontal cortex is a key node in the distributed cortical network recruited during WM (Owen et al. 2005;Fuster 2008) and exhibits altered inhibitory microcircuitry in schizophrenia (Lewis et al. 2005;Bitanihirwe et al. 2009).”
From Linking microcircuit dysfunction to cognitive impairment: Effects of disinhibition associated with schizophrenia in a cortical working memory model (2014) · cites this paper as Lewis et al. 2005
In the citing paper
“Elevated prefrontal E/I ratio may result from alterations in multiple pathways that are implicated in schizophrenia.These include GABAergic deficits, such as reduced GAD67 production (Lewis et al. 2005); increased background input from other areas such as the thalamus or hippocampus (Lisman et al. 2008); or abnormal levels of neuromodulators (Laruelle et al. 2003).”
From Linking microcircuit dysfunction to cognitive impairment: Effects of disinhibition associated with schizophrenia in a cortical working memory model (2014) · cites this paper as Lewis et al. 2005
In the citing paper
“Both interneuron cell classes are altered in schizophrenia (Lewis et al. 2005;Morris et al. 2008;Bitanihirwe et al. 2009).”
From Linking microcircuit dysfunction to cognitive impairment: Effects of disinhibition associated with schizophrenia in a cortical working memory model (2014) · cites this paper as Lewis et al. 2005
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“Of note, as far as we are aware, this is the first experimental demonstration that “neonatal” interaction of major genetic and environmental susceptibility factors for schizophrenia results in the dramatic change in the parvalbumin-positive interneurons in the medial prefrontal cortex (mPFC), one of the best hallmarks…”
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Metadata
- Authors
- Lewis, D. A., Hashimoto, T., & Volk, D. W.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Lewis, David A.
- Venue
- Nature Reviews Neuroscience
- Published
- 2005-04
- Volume
- 6
- Issue
- 4
- Pages
- 312-324
- ISSN
- 1471-003X (ISSN-L)
- 1471-0048
- OpenAlex
- W2089912569
- Cited by
- 2,297
- References
- 123
- Citations by year
- 2026: 36 · 2025: 51 · 2024: 63 · 2023: 48 · 2022: 70 · 2021: 86 · 2020: 77 · 2019: 94 · 2018: 102 · 2017: 89 · 2016: 123 · 2015: 148 · 2014: 132 · 2013: 167 · 2012: 151
- FWCI
- 16.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- schizophrenia, cortical inhibitory neurons, parvalbumin interneurons, GABA synthesis, dorsolateral prefrontal cortex, working memory, perisomatic inhibition, cognitive impairment
- MeSH terms
- Animals, Cerebral Cortex, Humans, Nerve Net, Neural Inhibition, Neurons, Schizophrenia
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