Cited by 406Schizophrenia research and treatmentNeuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on Behavior

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Cognitive Dysfunction in Schizophrenia: Convergence of γ-Aminobutyric Acid and Glutamate Alterations

Lewis, David A., Moghaddam, Bita·2006·Archives of Neurology

DOI 10.1001/archneur.63.10.1372

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Abstract

Impairments in certain cognitive functions mediated by the dorsolateral prefrontal cortex, such as working memory, are core features of schizophrenia. Convergent findings suggest that these disturbances are associated with alterations in markers of inhibitory gamma-aminobutyric acid and excitatory glutamate neurotransmission in the dorsolateral prefrontal cortex. Specifically, reduced gamma-aminobutyric acid synthesis is present in the subpopulation of gamma-aminobutyric acid neurons that express the calcium-binding protein parvalbumin. Despite presynaptic and postsynaptic compensatory responses, the resulting impaired inhibitory regulation of pyramidal neurons contributes to a reduction in the synchronized neuronal activity that is required for working memory function. Several lines of evidence suggest that these changes may be either secondary to or exacerbated by impaired signaling via the N-methyl-d-aspartate class of glutamate receptors. These findings suggest specific targets for therapeutic interventions to improve cognitive function in individuals with schizophrenia.

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Authors: Lewis, D. A., & Moghaddam, B.
Affiliations: University of Pittsburgh (US)
ORCID: Lewis, David A.
Moghaddam, Bita
Venue: Archives of Neurology
Publisher: American Medical Association (AMA)
Published: 2006-10-01
Volume: 63
Issue: 10
Pages: 1372
ISSN: 0003-9942 (ISSN-L)
DOI: 10.1001/archneur.63.10.1372
OpenAlex: W2037549116
Cited by: 404
References: 41
Citations by year: 2026: 4 · 2025: 5 · 2024: 11 · 2023: 6 · 2022: 9 · 2021: 11 · 2020: 11 · 2019: 12 · 2018: 16 · 2017: 13 · 2016: 17 · 2015: 22 · 2014: 28 · 2013: 25 · 2012: 39
FWCI: 20.65
Type: journal article
Language: en
Open access: closed
Locations: Archives of Neurology (publishedVersion)
PubMed (publishedVersion)
Funders: University of Pittsburgh
National Alliance for Research on Schizophrenia and Depression
National Institutes of Health (5r01mh048404-30, MH043784, MH045156)
National Institute of Mental Health (MH-045156, R01-MH048404, MH051234, R37MH048404, R01MH051234, P50MH045156, MH065026, R21MH065026, MH043784, MH048404)
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, cognitive impairment, working memory, dorsolateral prefrontal cortex, GABAergic inhibition, glutamatergic excitation, parvalbumin, NMDA receptor, neuronal synchronization, therapeutic target
MeSH terms: Animals, Cognition Disorders, gamma-Aminobutyric Acid, Humans, Neural Inhibition, Synaptic Transmission, Schizophrenia, Receptors, N-Methyl-D-Aspartate, Prefrontal Cortex, Pyramidal Cells, Glutamic Acid

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Cognitive Dysfunction in Schizophrenia: Convergence of γ-Aminobutyric Acid and Glutamate Alterations

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