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June 1997

N-Methyl-D-Aspartate Receptor Hypofunction in Schizophrenia Could Arise From Reduced Cortical Connectivity Rather Than Receptor Dysfunction

Author Affiliations

Yale Psychiatric Institute PO Box 208038 New Haven, CT 06520-8038

Arch Gen Psychiatry. 1997;54(6):578-579. doi:10.1001/archpsyc.1997.01830180096017

An article by Olney and Farber1 outlines an intriguing theory of schizophrenia based on studies of the glutamate N-methyl-D-aspartate (NMDA) receptor. Their model relies on the observation that NMDA antagonists such as phencyclidine hydrochloride can induce psychoticlike symptoms in human subjects and has demonstrated neurotoxic reactions in animals. The latter could provide an explanation for the downhill course of many patients with schizophrenia. Their model also notes that dopamine is known to inhibit glutamate release, an observation that suggests a possible therapeutic action, namely, disinhibition of glutamate release, of dopamine-blocking antipsychotic drugs. The authors postulate that NMDA receptor dysfunction underlies the pathology of schizophrenia.

Other recent studies suggest that NMDA receptor hypofunction in schizophrenia may derive not from re

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