Glutamate in schizophrenia

Kim JS, Kornliuber HH, Schmid-Burgk W, Holzmuller B (1980) Low cerebrospinal fluid glutamate in schizophrenia padents and a new hypo diesis of glutamatergic neiu onal dysfuncdon. Neiu osci Lett 20 379-382. 

Buzsaki G, Chrobak JJ (1995) Temporal structiu e in spatially organized neimonal ensembles a role for internem onal networks. Cimr Opin Neurobiol 5 504-510 Carlsson A, Waters N, Holm-Waters S, Tedroff J, Nilsson M, Carlsson ML (2001) Interactions between monoamines, glutamate, and GABA in schizophrenia new evidence. Annu Rev Pharmacol Toxicol 41 237-260... 

Carlsson A et al. Interactions between monoamines, glutamate, and GABA in schizophrenia new evidence. Annu Rev Pharmacol Toxicol 2001 41 237-260. 

Guidotti, A., Auta, J., Davis, J.M., Gerevini, V.D., Dwivedi, Y., Grayson, D.R., Impagnatiello, E, Pandey, G., Pesold, C., Sharma, R., Uzunov, D., and Costa, E. (2000) Decrease in reelin and glutamic acid decarboxylase 67 (GAD67) expression in schizophrenia and bipolar disorder a postmortem brain study. Arch Gen Psychiatry 57 1061-1069. 

Abnormalities of the glutamate system have also been documented in neuropsychiatric disorders. For example, compounds such as PCP and ketamine, which block the NMDA receptor, can induce psychotic symptoms. By contrast, compounds such as d-cycloserine or glycine, which increase NMDA receptor function via the glycine binding site, can decrease psychotic and/or negative symptoms in schizophrenia (Farber et ah, 1999 Goff et ah, 1999, Fleresco-Levy et ah, 1999). 

Glutamate was initially implicated in schizophrenia by studies of the behavioral effects of N-methyl-D-aspartate (NMDA) receptor antagonists (e.g., PCP, ketamine), which produce psychotic symptoms and cognitive dysfunction in healthy subjects and exacerbate psychotic, negative, and cognitive symptoms in patients with schizophrenia. Studies show that acute administration of NMDA antagonists causes NMDA receptor dysfunction, resulting in decreased inhibition of subcortical dopamine neurons and consequent increased mesolimbic dopamine release. Chronic administration produces decreased release, or hypoactivity, of dopamine in the prefrontal cortex (Davis and Lieberman, 2000). 

Leriche L, DiazJ, Sokoloff P. Dopamine and glutamate dysfunctions in schizophrenia role of... 

In addition to an abnormality in the corticostriatal system, it is also possible that a disorder in the dopamine-glutamate system occurs in other subcortical regions which could account for some of the symptoms seen in schizophrenia. The hippocampus and the associated entorhinal cortex are important areas of the brain concerned in memory formation, information... 

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