The binding of [H-3]AF-DX 384 is reduced in the Caudate-Putamen of subjects with schizophrenia

Clinical studies of cholinergic pharmacotherapy, together with the putative role of the muscarinic receptor system in the neurophysiology of human beh avior, support a possible muscarinic cholinergic involvement in schizophren ia. The present study has measured the density of [H-3]AF-DX 384 labelled r eceptors (muscarinic M-2 and M-4) in the caudate-putamen, obtained at autop sy, from 19 subjects who had schizophrenia, and 20 subjects who did not hav e schizophrenia. [H-3]AF-DX 384 binding was reduced in caudate-putamen from schizophrenic subjects (104 +/- 10.3 v(s) 145 +/- 901 fmol mg(-1) TE; mean +/- s.e.; p = 0.007). Preliminary analysis of patient drug data as well as rat studies suggest that the reduced [H-3]AF-DX 384 binding in caudate-put amen of schizophrenic subjects is not wholly due to antipsychotic drug trea tment, or anticholinergic medication for the treatment of extrapyramidal ef fects. These data suggest that the muscarinic cholinergic system may be inv olved in the pathology of schizophrenia.