Altered cortical GABA neurotransmission in schizophrenia: Insights into novel therapeutic strategies

Ana D. Stan, David A. Lewis

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


Altered markers of cortical GABA neurotransmission are among the most consistently observed abnormalities in postmortem studies of schizophrenia. The altered markers are particularly evident between the chandelier class of GABA neurons and their synaptic targets, the axon initial segment (AIS) of pyramidal neurons. For example, in the dorsolateral prefrontal cortex of subjects with schizophrenia immunoreactivity for the GABA membrane transporter is decreased in presynaptic chandelier neuron axon terminals, whereas immunoreactivity for the GABAA receptor α2 subunit is increased in postsynaptic AIS. Both of these molecular changes appear to be compensatory responses to a presynaptic deficit in GABA synthesis, and thus could represent targets for novel therapeutic strategies intended to augment the brain's own compensatory mechanisms. Recent findings that GABA inputs from neocortical chandelier neurons can be powerfully excitatory provide new ideas about the role of these neurons in the pathophysiology of cortical dysfunction in schizophrenia, and consequently in the design of pharmacological interventions.

Original languageEnglish (US)
Pages (from-to)1557-1562
Number of pages6
JournalCurrent Pharmaceutical Biotechnology
Issue number8
StatePublished - Jun 2012


  • Basket neuron
  • Chandelier neuron
  • GABA-A receptor
  • Parvalbumin
  • Prefrontal cortex

ASJC Scopus subject areas

  • Biotechnology
  • Pharmaceutical Science


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