Neuropsychological deficits in nonsmokers with schizophrenia: effects of a nicotinic antagonist.
Neuropsychological deficits in nonsmokers with schizophrenia: effects of a nicotinic antagonist.
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精神分裂症非吸烟者的神经心理缺陷：烟碱拮抗剂的作用。
DOI：
10.1016/j.schres.2006.03.025
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发表时间：
2006
影响因子：
4.5
通讯作者：
George,TonyP
中科院分区：
文献类型：
--
作者：
Sacco,KristiA;Termine,Angelo;Dudas,MelissaM;Seyal,AishaA;Allen,TarynM;Vessicchio,JenniferC;Wexler,BruceE;George,TonyP
背景生化、生理学和遗传学证据表明，精神分裂症患者中枢烟碱型乙酰胆碱受体(NAChR)系统功能失调，这可能是导致精神分裂症患者神经心理功能障碍和高吸烟率的原因之一。为评价nAChR受体阻滞剂对无吸烟混杂效应的精神分裂症患者神经心理功能的影响，我们比较了中枢作用的nAChR拮抗剂甲氨基甲胺(MEC)对精神分裂症患者和健康对照非吸烟者神经心理功能的影响。方法采用受试者内平衡设计，对14例精神分裂症患者和15例非吸烟者分别给予MEC(0.0、5.0和10.0 mg/d)治疗3d。结果发现精神分裂症诊断的主要影响因素为：视觉空间工作记忆(VSWM)、连续操作测验(CPT)、威斯康星卡片分类测验(WCST)、单词连续位置测验(WSPT)和Stroop颜色词测验(SCWT)。0.01)。然而，重复试验给药(SESSION)或MEC剂量对这些结果中的任何一个都没有主效应，也没有显著的三向(诊断×SESSION×MEC剂量)交互作用。结论研究结果表明，精神分裂症患者存在广泛的神经心理缺陷。此外，中枢作用的nAChR拮抗剂的预治疗不会改变患有精神分裂症的不吸烟患者或对照组的神经心理表现。
BACKGROUNDBiochemical, physiological and genetic evidence suggests dysregulation of central nicotinic acetylcholine receptor (nAChR) systems in schizophrenia, which may contribute to neuropsychological dysfunction and the high rates of smoking in this disorder. To evaluate the effects of nAChR blockade on neuropsychological performance in schizophrenia without the confounding effects of cigarette smoking, we compared neuropsychological performance in schizophrenia and healthy control nonsmokers after pre-treatment with the centrally-acting nAChR antagonist mecamylamine (MEC).METHODSUsing a within-subjects, counterbalanced design, schizophrenia (n=14) and control (n=15) nonsmokers were pre-treated for 3 days with MEC (0.0, 5.0, and 10.0 mg/day). Subjects performed repeated neuropsychological assessments including visuospatial working memory (VSWM), Continuous Performance Test (CPT), Wisconsin Card Sorting Test (WCST), Word Serial Position Test (WSPT) and Stroop Color Word Test (SCWT) during three sequential test sessions per week over three test weeks.RESULTSWe found significant main effects of schizophrenia diagnosis on: VSWM 30 and 60 delays (p's<0.01), CPT (% Hit Rate, Reaction Time, Variability Index; p<0.01 for all outcomes), WCST (p<0.01 for all outcomes) and Word Serial Position Test (p<0.01). However, there were no main effects of repeated test administration (Session) or MEC dose on any of these outcomes, and no significant 3-way (Diagnosis×Session×MEC dose) interactions.CONCLUSIONSOur results suggest that there are a broad range of neuropsychological deficits in nonsmokers with schizophrenia. Furthermore, pretreatment with a centrally-acting nAChR antagonist did not alter neuropsychological performance in either nonsmoking patients with schizophrenia or controls.