A Role for Glutamate Receptors, Transporters, and Interacting Proteins in Cortical Dysfunction in Schizophrenia

While there are myriad genetic, environmental, and epigenetic risk factors for schizophrenia, there is broad consensus that abnormal glutamate neurotransmission has a role in the ultimate clinical manifestations of this devastating illness. The glutamate hypothesis has evolved beyond the simplistic notion of NMDA receptor dysfunction, based in part on the dearth of consistently reproducible findings for altered NMDA receptor and binding site expression in postmortem studies. In this review, we review cortical glutamate receptor expression in this illness, and highlight postmortem data from novel families of glutamate receptor interacting proteins. We also discuss the vesicular and plasma membrane glutamate transporters, and review studies that have examined cortical glutamate transporter expression in this illness. Finally, we discuss the hypothesis that trafficking, assembly of signaling complexes, and receptor recycling might be dysregulated and represent important new targets for pharmacological manipulation in the treatment of schizophrenia.