Nicotinic Receptors and Cog Function in Schizophrenia

描述(申请人提供)：精神分裂症患者的患病率很高 吸烟的比例(58%-88%)与一般人口(-25%)相比 )，而且通常是尼古丁依赖吸烟者，他们有相当大的 戒烟有困难。有几个因素可能会使这些患者容易患上 吸烟包括缓解烦躁不安的情绪状态，改善 锥体外系症状和信息处理缺陷 神经心理功能，以及决定 易患尼古丁依赖和精神分裂症。精神分裂症患者 患者有认知功能缺陷，包括执行功能 (威斯康星卡片分类测验；WCST)，言语和空间工作记忆 视觉空间工作记忆(VSWM)]，反应抑制(Stroop颜色词 测试(SCWT)、注意力和专注力(持续性能测试；CPT)和 信息处理{惊吓反应的预脉冲抑制(PPI)}。 初步证据表明，吸烟可以改善，而且 禁欲会恶化精神分裂症患者的认知功能。尼古丁 戒断与中枢多巴胺(DA)的减少有关 在动物和人体研究中的作用，上述任务中的几项是 这部分依赖于前额叶皮质的DA功能。我们的初步结果 提示戒烟对大鼠视空间工作记忆(VSWM)的损害 精神分裂症吸烟者，但改善健康吸烟者的VSWM。然而， 吸烟和戒烟对老年人认知功能的影响 精神分裂症患者与健康吸烟者之间的关系尚未得到仔细评估。 在目前的研究中，我们将评估吸烟和吸烟的影响 在已知的精神分裂症患者认知测试中存在禁欲， 包括神经心理测试(WCST、SCWT、CPT、WSPT、VSWM)和PPI。之后 基线测试，精神分裂症患者(n=25)和健康对照组(n=25)吸烟者将 接受彻夜戒烟，然后重复测试，然后 恢复吸烟后的后续检测。一组精神分裂症患者(n=25) 健康的(n=25)非吸烟者将作为对照并完成同样的研究 测试的顺序。我们还将评估高亲和力尼古丁的作用 乙酰胆碱受体(NAChRs)，使用nAChR拮抗剂预处理 甲基戊胺(0.0、5.0和10.0 mg/d)在香烟效应中的作用 在这些认知评估中吸烟。因此，这些研究可以提供 吸烟改变人认知功能的机制的数据 精神分裂症患者与对照吸烟者，并提出新的治疗方法 精神分裂症患者的尼古丁依赖和认知功能障碍。

DESCRIPTION(provided by applicant): Schizophrenics have high prevalence rates of cigarette smoking (58-88 percent) compared to the general population (-25 percent), and are often nicotine-dependent smokers who have considerable difficulty quitting smoking. Several factors may predispose these patients to cigarette smoking including alleviation of dysphoric mood states, improvements in extrapyramidal symptoms and deficits in information processing and neuropsychological function, as well as genetic factors that determine a vulnerability to both nicotine dependence and schizophrenia. Schizophrenic patients have deficits in cognitive function, including executive function (Wisconsin Card Sorting Test; WCST), verbal and spatial working memory Visuospatial Working Memory (VSWM)], response inhibition (Stroop Color-Word Test; SCWT), attention and concentration (Continuous Performance Test; CPT) and information processing {prepulse inhibition (PPI) of the startle response}. Preliminary evidence suggests that cigarette smoking can improve, and abstinence can worsen, cognitive function in schizophrenic patients. Nicotine withdrawal has been associated with reductions in central dopamine (DA) function in animal and human studies, and several of the above tasks are dependent, in part, on prefrontal cortical DA function. Our preliminary results suggest that smoking abstinence impairs visuospatial working memory (VSWM) in schizophrenic smokers, but improves VSWM in healthy smokers. However, the effects of cigarette smoking and abstinence on cognitive function in schizophrenic vs. healthy smokers have not been carefully evaluated. In the present studies, we will evaluate the effects of cigarette smoking and abstinence on cognitive tests known to be deficient in schizophrenic patients, including neuropsychological tests (WCST, SCWT, CPT, WSPT, VSWM) and PPI. After baseline testing, schizophrenic (n=25) and healthy control (n=25) smokers will undergo overnight smoking abstinence, followed by repeat testing, and then subsequent testing after resuming smoking. A group of schizophrenic (n=25) and healthy (n=25) non-smokers will serve as controls and complete the same sequence of testing. We will also assess the role of high-affinity nicotinic acetylcholine receptors (nAChRs), using pre-treatment with the nAChR antagonist mecamylamine (0.0, 5.0 and 10.0 mg/day), in mediating the effect of cigarette smoking on these cognitive assessments. Accordingly, these studies may provide data on the mechanisms by which cigarette smoking alters cognitive function in schizophrenic vs. control smokers, and suggest novel treatment approaches for both nicotine dependence and cognitive dysfunction in schizophrenic disorders.