Glutamate and Schizophrenia

Schizophrenia is a complex and chronic disease that affects multiple aspects of cognition and behavior, including attention, perception, thought processes, emotion and volition. However, the pathophysiology of schizophrenia has not yet been fully clarified. For more than a decade, the dopamine hypothesis has been the most influential hypothesis in schizophrenia research. It postulates that schizophrenia is a manifestation of a hyperdopaminergic state in some regions of the brain. However, several studies have reported results that are inconsistent with the dopamine theory of schizophrenia and it is now believed that other neurotransmitter systems are probably involved. Interest in the role of excitatory amino acids in schizophrenia is rapidly increasing. Excitatory amino acids and their receptors are thought to play a role in the pathology of schizophrenia, based on several lines of evidence, such as the psychomimetic effects of glutamate receptor antagonists in non-schizophrenic subjects and patients with schizophrenia, postmortem studies of reporting changes in glutamate receptors in schizophrenia, and studies that have treated schizophrenic patients with glutamate receptor agonists. This review will focus on clinical evidence contributing to the “glutamate hypothesis of schizophrenia”.