Abnormal kainate receptor expression in prefrontal cortex in schizophrenia

Abnormalities of molecules associated with the glutamate synapse have been implicated in the pathophysiology of schizophrenia. Of the many glutamate r eceptors, those most commonly suggested to be involved in schizophrenia are the ionotropic subtypes, the NMDA, AMPA, and kainate receptors. Both the N MDA and AMPA subtypes have berl? extensively studied in postmortem brains o f individuals with schizophrenia, but relatively little is known about the expression of the kainate subtype of glutamate receptor. In this study, we have determined cortical and striatal kainate receptor expression in brains from persons with schizophrenia and a comparison group, using both in situ hybridization and receptor autoradiography. At the level of subunit mRNA e xpression, a shift in subunit stoichiometry teas evident in multiple region s of the prefrontal cortex, with increased expression of gluR7 mRNA and dec reased expression of KA2 mRNA. Decreased kainate receptor binding was also observed in the subjects with schizophrenia, but was restricted to infragra nular laminae of tire prefrontal cortex. No differences in kainate receptor binding or subunit mRNA levels were found ill striatum or occipital cortex , suggesting that these findings may be restricted to association cortex. T hese data add to the gr growing literature implicating ionotropic glutamate receptor disturbances in schizophrenia, and indicate that in addition to A MPA and NMDA receptors, the kainate receptors are also abnormally expressed in this illness. (C) 2001 American College of Neuropsychopharmacology. Pub lished by Elsevier Science Inc.