Decreased muscarinic receptor binding in subjects with schizophrenia: A study of the human hippocampal formation

Background: Acetylcholine is important to hippocampal function, including t he processes of learning and memory. Patients with schizophrenia show impai red learning and memory and hippocampal dysfunction. Thus, acetylcholinergi c systems may be primarily or secondarily disrupted in the hippocampal form ation of schizophrenic patients, The present study tested the hypothesis th at [H-3]pirenzepine-labeled muscarinic cholinergic receptor levels are alte red in the hippocampal formation of patients with schizophrenia, Methods: We have used quantitative autoradiography to measure [H-3]pirenzep ine binding to M-1 and M-4 receptors in the hippocampal formation from 15 s chizophrenic and IS nonschizophrenic subjects. Results: The mean density of [H-3]pirenzepine binding was reduced in all re gions studied including the dentate gyrus, subdivisions of Ammon's Horn (CA 1-CA4), subiculum, and the parahippocampal gyrus, of the schizophrenic coho rt. Moreover, unlike controls, there was no significant variation between t he mean levels of [H-3]pirenzepine binding across the subregions of the hip pocampal formation from schizophrenic subjects, Conclusions: These findings provide support for a possible involvement of t he muscarinic cholinergic system in the pathology and/or treatment of schiz ophrenia. (C) 2000 Society of Biological Psychiatry.