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Annotation

Lewis DA, Cho RY, Carter CS, Eklund K, Forster S, Kelly MA, Montrose D. Subunit-selective modulation of GABA type A receptor neurotransmission and cognition in schizophrenia. Am J Psychiatry . 2008 Dec ; 165(12):1585-93. PubMed Abstract

Comments on Paper and Primary News
Primary News: GABA Receptor Drug for Schizophrenia Is Put Through Its Paces

Comment by:  Robert McCarley
Submitted 7 November 2008 Posted 7 November 2008

This paper is further evidence of an important and laudable new trend in schizophrenia psychopharmacology: namely the development and test of compounds on the basis of their relationship to circuit abnormalities, evidence derived from postmortem, genetic, and animal model studies. The authors based their choice of MK-0777 for test in schizophrenia on evidence for decreased cortical GABA neurotransmission onto pyramidal neurons at receptors having the α2 subunit, and other evidence pointing to the GABA-pyramidal neuron interaction as important in cognition and in generation of γ band oscillations. In this add-on, double-blind placebo study, the Ns were underpowered and more subjects need to be studied to be certain about clinical effects. However, one test, the Preparing to Overcome Prepotency Test (POP), had significant improvements in response latency and showed concomitant improvement in increased frontal γ band activity induced during the task, although not meeting the criterion for statistical significance. POP requires subjects either to “go with the flow”...  Read more


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