Tandon R, Shipley J E, Greden J F, Mann N A, Eisner W H, Goodson J A
Department of Psychiatry, University of Michigan Medical Center, Ann Arbor 48109-0120.
Schizophr Res. 1991 Jan-Feb;4(1):23-30. doi: 10.1016/0920-9964(91)90006-d.
Based on the implication of increased muscarinic ACh activity in the production of negative symptoms, the association of decreasing cholinergic activity with positive symptoms, and the covariance of positive and negative symptoms in the psychotic phase of schizophrenia, a model of (DA) dopaminergic/(ACh) cholinergic interactions in schizophrenia was recently formulated. It suggests that DA/ACh balance is of central importance in schizophrenic pathophysiology and that muscarinic ACh activity increases in an attempt to maintain this balance in the face of increasing DA activity that occurs in the psychotic phase of the illness. The model further suggests that the muscarinic system exerts a damping influence on the emergence of positive symptoms associated with DA hyperactivity, but that this compensatory increase in muscarinic activity is accompanied by an intensification of negative symptoms. In the present study, we tested two important postulates of this model. We tested the prediction that muscarinic activity is increased in schizophrenia by comparing the effect of biperiden, an antimuscarinic M-1 agent, on REM latency in 12 drug-free schizophrenic inpatients and matched normal controls. We found that biperiden caused a smaller increase in REM latency in schizophrenic patients, suggesting that muscarinic activity is increased in schizophrenia. We tested the prediction that an anticholinergic agent would increase positive symptoms and decrease negative symptoms by studying the effect of 8 mg of biperiden/day for 2 days on positive and negative symptoms (assessed by the BPRS) in 30 medication-free schizophrenic inpatients.(ABSTRACT TRUNCATED AT 250 WORDS)
基于毒蕈碱型乙酰胆碱（ACh）活性增加与阴性症状产生之间的关联、胆碱能活性降低与阳性症状之间的关联，以及精神分裂症精神病性阶段阳性和阴性症状的协变性，最近构建了一个精神分裂症中多巴胺能（DA）/胆碱能（ACh）相互作用的模型。该模型表明，DA/ACh平衡在精神分裂症的病理生理学中至关重要，并且在疾病的精神病性阶段，面对DA活性增加，毒蕈碱型ACh活性会增加以维持这种平衡。该模型还进一步表明，毒蕈碱系统对与DA功能亢进相关的阳性症状的出现具有抑制作用，但这种毒蕈碱活性的代偿性增加伴随着阴性症状的加重。在本研究中，我们测试了该模型的两个重要假设。我们通过比较抗毒蕈碱M-1药物安坦对12名未服药的精神分裂症住院患者和匹配的正常对照者快速眼动睡眠潜伏期的影响，来测试精神分裂症中毒蕈碱活性增加这一预测。我们发现安坦使精神分裂症患者的快速眼动睡眠潜伏期增加幅度较小，表明精神分裂症中毒蕈碱活性增加。我们通过研究每天8毫克安坦，连续2天对30名未服药的精神分裂症住院患者的阳性和阴性症状（通过简明精神病评定量表评估）的影响，来测试抗胆碱能药物会增加阳性症状并减少阴性症状这一预测。（摘要截选至250词）
