Cognitive dysfunction in schizophrenia: Convergence of γ-aminobutyric acid and glutamate alterations

David A. Lewis, Bita Moghaddam

Research output: Contribution to journalReview article

307 Citations (Scopus)

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 γ-aminobutyric acid and excitatory glutamate neurotransmission in the dorsolateral prefrontal cortex. Specifically, reduced γ-aminobutyric acid synthesis is present in the subpopulation of γ-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.

Original languageEnglish (US)
Pages (from-to)1372-1376
Number of pages5
JournalArchives of Neurology
Volume63
Issue number10
DOIs
StatePublished - 2006
Externally publishedYes

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Aminobutyrates
Glutamic Acid
Schizophrenia
Prefrontal Cortex
Short-Term Memory
Cognition
Parvalbumins
Calcium-Binding Proteins
Pyramidal Cells
Glutamate Receptors
N-Methylaspartate
Synaptic Transmission
Neurons
Cognitive Dysfunction
Cognitive Function
Working Memory
Neuron
Alteration
Therapeutics
Protein

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Cognitive dysfunction in schizophrenia : Convergence of γ-aminobutyric acid and glutamate alterations. / Lewis, David A.; Moghaddam, Bita.

In: Archives of Neurology, Vol. 63, No. 10, 2006, p. 1372-1376.

Research output: Contribution to journalReview article

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