Further postmortem autoradiographic studies of AMPA receptor binding in schizophrenia

Previous research indicated an increased binding of AMPA receptor ligand [(3)H]CNQX at 50 nM in the caudate nucleus of schizophrenics and suicides relative to normal and neuroleptic-treated controls. The current work aimed to replicate this finding in a larger, independent sample of schizophrenics and controls. In addition to neostriatal structures, the hippocampal region and amygdala were also studied. Postmortem frozen sections from 15 schizophrenics (four suicides), 15 normal controls, 15 bipolars (eight suicides), and 15 unipolar nonpsychotic depressed (seven suicides) subjects were studied with quantitative autoradiographic procedures at 5, 20, and 50 nM [(3)H]CNQX in the striatum and at 20 nM in medial temporal structures. [(3)H]KA (kainic acid) binding was also examined. Instead of an expected increase, schizophrenics in this sample have a lower degree of [(3)H]CNQX binding in caudate and nucleus accumbens at 20 nM and in the nucleus accumbens at 50 nM, with suicided schizophrenics having higher binding than nonsuicided schizophrenics at the 20 nM concentration of [(3)H]CNQX in the caudate. [(3)H]CNQX binding was uniform across diagnostic categories at 5 nM in the striatum and at 20 nM in amygdala and hippocampal structures. KA receptor binding also did not differ among groups in any structures examined. These assays in a larger sample at three different concentrations do not support the previously reported increase in binding to AMPA receptors in schizophrenia but rather indicate an abnormal decrease in binding to this receptor in this sample. Possible explanations for the disparity in results between the two studies are considered. The data continue to indicate pathology of AMPA glutamate receptors in striatal structures in schizophrenia; however, it may be variable and its precise nature remains to be clarified.