Project Summary

Anirvan Ghosh, Ph.D. (Independent Investigator 2002) of Johns Hopkins University, is testing the hypothesis that developmental abnormalities in the function of the NMDA subtype of glutamate receptors can lead to lasting alteration in cortical circuitry, which in turn can cause behavioral abnormalities characteristic of schizophrenic disorder.  Episodic positive symptoms, such as delusions, hallucinations, and paranoia, reveal gross alteration in perceptual processing.  These can be accompanied by persistent negative symptoms ranging from impairment of attention, to social deficits and depressed emotive response.    Various lines of research support the possibility that NMDA receptor dysfunction may contribute to schizophrenia.  In mice, reduced expression of the NR1 subunit of NMDA receptor results in behavior associated with schizophrenia, and these symptoms can be successfully ameliorated with haloperidol or clozapine.   Therapeutic enhancement of NMDA function has been attempted as a treatment for schizophrenia.  Dr. Ghosh will generate two lines of mice that have altered subunit properties, and will use his findings to explore the physiological significance of the developmental switch in NMDA receptor subunits in cortex and to determine if alteration of this genetic switch can lead to symptoms characteristic of schizophrenia. 

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia

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