A PIVOTAL ROLE FOR GLUTAMATE IN THE PATHOGENESIS OF SCHIZOPHRENIA, AND ITS COGNITIVE DYSFUNCTION

There is mounting evidence of a glutamate dysfunction in schizophrenia , as suggested by the fact that schizophrenia and phencyclidine psycho sis are similar and phencyclidine is known to block the N-methyl-D-asp artate (NMDA) subtypes of glutamate. Both occur mainly after puberty, suggesting they may share similar underlying developmental processes. Direct evidence is now accumulating from the study of messenger RNA th at glutamate receptor deficiencies occur in schizophrenia and are regi onally and specifically distributed. These results find support from s tudies of memory, electrophysiological findings, clinical treatment, a nd pharmacological studies in mammals and humans. Our recent findings of: a) a marked decrease in pyramidal cell dendritic spines in layer I II of the frontal and temporal cortex, and b) a greater than 0.90 corr elation between decrease in mRNA for the NMDA glutamate receptor and c ognitive deterioration in elderly schizophrenics, present the stronges t evidence to date that glutamate dysfunction plays an important role in schizophrenia. (C) 1997 Elsevier Science Inc.