title: Converging evidence of NMDA receptor hypofunction in the pathophysiology of schizophrenia.
abstract: Numerous clinical studies demonstrate that subanesthetic doses of dissociative anesthetics, which are noncompetitive antagonists at the NMDA receptor, replicate in normal subjects the cognitive impairments, negative symptoms, and brain functional abnormalities of schizophrenia. Postmortem and genetic studies have identified several abnormalities associated with schizophrenia that would interfere with the activation of the glycine modulatory site on the NMDA receptor. Placebo-controlled clinical trials with agents that directly or indirectly activate the glycine modulatory site consistently reduce negative symptoms and frequently improve cognition in patients with chronic schizophrenia who are receiving concurrent typical antipsychotics. Thus, there is convincing evidence that hypofunction of a subset of NMDA receptors may contribute to the symptomatic features of schizophrenia.
authors.affiliation: McLean Hospital, Belmont, Massachusetts 02478, USA. joseph_coyle@hms.harvard.edu
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Coyle
authors.forename: Guochuan
authors.initials: G
authors.lastname: Tsai
authors.forename: Donald
authors.initials: D
authors.lastname: Goff
mesh_terms: D014150:Antipsychotic Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D006801:Humans; D017470:Receptors, Glutamate / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D012559:Schizophrenia / Q000188:drug therapy / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D014150:Antipsychotic Agents; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D005680:gamma-Aminobutyric Acid