The Role of NMDA Receptors in Schizophrenia

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Currently approved agents to treat schizophrenia focus on dopamine D2 or serotonin 5-HT antagonism or partial agonism. However, this mechanism appears to primarily resolve positive symptoms of psychosis, yet negative and cognitive symptoms can persist even among patients who have responded to treatment. N-methyl-D-aspartate (NMDA) antagonists have been shown to produce symptoms across multiple domains, which may signal that NMDA receptors are a novel treatment target for the comprehensive management of schizophrenia. NMDA is an ionotropic glutamate receptor involved in several neurobiological processes, and NMDA receptor hypofunction can lead to sensory deficits, generalized cognitive deficits, impaired learning and memory, thought disorder, negative symptoms, positive symptoms, gating deficits, executive dysfunction, and dopamine dysregulation.

From the Department of Psychiatry, The Zucker Hillside Hospital, Glen Oaks; the Department of Psychiatry, Hofstra North Shore-Long Island Jewish School of Medicine, Uniondale; and Behavior Health Services, North Shore-Long Island Jewish Health System, New Hyde Park, New York.

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J Clin Psychiatry 2015;76(1):e1

https://doi.org/10.4088/JCP.13078tx5c