Glutamatergic aspects of schizophrenia

Almost all the neurons in the brain are influenced by the excitatory amino acid glutamate. Glutamatergic neurotransmission has been associated functio nally with a number of physiological processes and with certain pathophysio logical processes, including schizophrenia. Imaging studies provide indirec t evidence: that glutamate may be involved in schizophrenia. Positron emiss ion tomography scanning has shown a correlation between positive symptoms o f schizophrenia and abnormalities of glucose metabolism in components of th e limbic system with the highest concentration of glutamate receptors. Stud ies with ketamine, an anaesthetic that antagonises the N-methyl-D-aspartate (NMDA) glutamate receptor, show an exacerbation or worsening of positive s ymptoms when this drug is administered to patients with schizophrenia. Regi onal cerebral blood flow studies with ketamine show that the drug produces increased blood flow in the anterior cingulate cortex, the! area where high concentrations of NMDA receptors exist and where alterations in glucose me tabolism seem to occur in people with schizophrenia, Diminished glutamaterg ic neurotransmission in the hippocampal gluatamate-mediated efferent pathwa ys and cerebral dysfunction in the hippocampus and its target areas. partic ularly the anterior cingulate cortex, may underlie some of the clinical man ifestations of schizophrenia.