Nature Reviews Neuroscience 6, 312-324 (April 2005) | doi:10.1038/nrn1648

Cortical inhibitory neurons and schizophrenia

David A. Lewis1,2, Takanori Hashimoto1 & David W. Volk1  About the authors


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.

Author affiliations

  1. Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
  2. Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.

Correspondence to: David A. Lewis1,2 Email:


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