Evidence of Glutamatergic Dysfunction in the Pathophysiology of Schizophrenia

Abstract

Abnormalities of the glutamate system are widely recognized to be involved in the pathophysiology of schizophrenia, though the exact mechanism is still unclear. Accumulating evidence from postmortem studies has implicated alterations in several components of glutamatergic synapses, including abnormalities of glutamate receptors and transporters. These data support the hypothesis that expression, trafficking, and downstream signaling pathways of N-methyl-D-aspartate (NMDA) receptors are altered in this illness. Changes in glutamate transporter expression suggest there may be chronic glutamate spillover from the synaptic cleft, leading to increased activation of extrasynaptic glutamate receptors. We propose that changes in NMDA-subtype glutamate receptor function and glutamate transporter expression are components of a common pathophysiological pathway leading to the schizophrenia phenotype.