The Cholinergic System in Schizophrenia Reconsidered:: Anticholinergic Modulation of Sleep and Symptom Profiles

Abstract

The role of the cholinergic system in schizophrenia remains controversial. A series of investigations are reviewed that describe the effects of pharmacological manipulation of the cholinergic system on schizophrenia symptomatology and whether putative measures of the cholinergic system are altered in schizophrenia. The effects of biperiden (an anticholinergic agent) on positive and negative symptoms of schizophrenia and on rapid eye movement (REM) latency and other sleep measures were assessed. Biperiden produced a significant increase in positive symptoms and a decrease in negative symptoms. REM latency was significantly shorter in schizophrenic patients and increased in both groups following biperiden. REM density decreased in a dose-dependent manner following biperiden in schizophrenic patients, but not in normal controls. The slope of REM density plotted against biperiden dose was inversely related to plasma homovanillic acid (HVA), an index of dopamine (DA) activity, in schizophrenic patients. These results further implicate the cholinergic system in schizophrenia pathophysiology and suggest a role for DA-acetylcholine (ACh) interactions in the production of sleep abnormalities and expression of positive and negative symptoms in schizophrenia.