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

Background: Acetylcholine is important to hippocampal function, including the processes of learning and memory. Patients with schizophrenia show impaired learning and memory and hippocampal dysfunction. Thus, acetylcholinergic systems may be primarily or secondarily disrupted in the hippocampal formation of schizophrenic patients. The present study tested the hypothesis that [³H]pirenzepine-labeled muscarinic cholinergic receptor levels are altered in the hippocampal formation of patients with schizophrenia. Methods: We have used quantitative autoradiography to measure [³H]pirenzepine binding to M₁ and M₄ receptors in the hippocampal formation from 15 schizophrenic and 18 nonschizophrenic subjects. Results: The mean density of [³H]pirenzepine binding was reduced in all regions studied, including the dentate gyrus, subdivisions of Ammon's Horn (CA1-CA4), subiculum, and the parahippocampal gyrus, of the schizophrenic cohort. Moreover, unlike controls, there was no significant variation between the mean levels of [³H]pirenzepine binding across the subregions of the hippocampal formation from schizophrenic subjects. Conclusions: These findings provide support for a possible involvement of the muscarinic cholinergic system in the pathology and/or treatment of schizophrenia. (C) 2000 Society of Biological Psychiatry.