Decreased density of muscarinic receptors in the superior temporal gyrusin schizophrenia

Recent studies have indicated that muscarinic receptors are involved in the pathophysiology in schizophrenia, particularly in cognitive deficits. The superior temporal gyrus (STG) is an area that has also been strongly implicated in the pathophysiology of schizophrenia. Therefore, in this study, we investigated the binding density of two muscarinic antagonists, [(3)H]pirenzepine and [(3)H]AF-DX 384, in the STG of schizophrenia patients compared with controls. A significant decrease (44% in the superficial layers and 48% in the deep layers, P<0.01) in binding density of [(3)H]pirenzepine was observed in schizophrenia patients, which suggested a reduction of muscarinic M1 and M4 receptor densities in the STG of schizophrenia patients. A tendency toward decreased [(3)H]AF-DX 384 binding density (34%, P=0.09) was also observed in schizophrenia patients compared with controls. Because of the positive correlation between [(3)H]pirenzepine and [(3)H]AF-DX 384 binding, and, insofar as both ligands have high affinities for the M4 receptor, the involvement of M4 receptor alteration is also suggested in the STG in schizophrenia. These results suggest that changes of the muscarinic receptors M1 and M4 might contribute to the STG pathology in schizophrenia.