title: The glutamate hypothesis: a pathogenic pathway from which pharmacological interventions have emerged.
abstract: We discuss the relevance of the glutamate hypothesis in explaining cognitive disturbances and negative symptoms in schizophrenia. 4 lines of evidence support the hypothesis that glutamate deregulation, mainly through dysfunction of the N-methyl-D-aspartate (NMDA) receptor, is an important underlying mechanism of schizophrenia. Glutamate pathways are promising sites for intervention. Glutamate agonists combined with non-clozapine antipsychotics and glutamate antagonists augmented to clozapine show interesting clinical benefits in refractory schizophrenia. We illustrate how unique properties of the NMDA receptor antagonist memantine in addition to clozapine, may cause improvement of positive, negative and cognitive symptoms of schizophrenia.
authors.affiliation: Mental Health Service Organisation North Holland North, Community Mental Health Division, Flexible Assertive -Community Treatment, Alkmaar, The Netherlands.
authors.forename: S R T
authors.initials: SR
authors.lastname: Veerman
authors.affiliation: Mental Health Service Organisation North Holland North, Division for Specialised Treatment, Treatment Centre for Bipolar Disorders, Alkmaar, The Netherlands.
authors.forename: P F J
authors.initials: PF
authors.lastname: Schulte
authors.affiliation: AMC, Academic Psychiatric Centre, Early Psychosis Department, Amsterdam, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: de Haan
mesh_terms: D003024:Clozapine / Q000494:pharmacology*; D016503:Drug Delivery Systems; D004359:Drug Therapy, Combination; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008559:Memantine / Q000494:pharmacology; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D012559:Schizophrenia / Q000209:etiology
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D003024:Clozapine; D008559:Memantine