Nicotinic Receptors and Cog Function in Schizophrenia

描述（由申请人提供）：精神分裂症的患病率很高 吸烟率（58%-88%）与普通人群（-25%）相比 %），并且通常是尼古丁依赖的吸烟者， 戒烟困难。有几个因素可能使这些患者倾向于 吸烟，包括缓解烦躁情绪状态，改善 锥体外系症状和信息处理缺陷， 神经心理学功能，以及遗传因素，决定了一个 易受尼古丁依赖和精神分裂症的影响。精神分裂 患者有认知功能缺陷，包括执行功能 （威斯康星州卡片分类测验; WCST）、言语和空间工作记忆 视觉空间工作记忆（VSWM）]、反应抑制（Stroop色词 注意力和集中力（连续性能测试; CPT）， 信息处理（惊吓反应的前脉冲抑制）。 初步证据表明，吸烟可以改善， 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）减少有关 在动物和人类研究中发挥作用，上述任务中有几项是 部分依赖于前额叶皮质DA功能我们的初步结果 表明戒烟损害视觉空间工作记忆（VSWM）， 精神分裂症吸烟者，但改善健康吸烟者的VSWM。但 吸烟和戒烟对认知功能的影响 精神分裂症患者与健康吸烟者的对比尚未得到仔细评估。 在目前的研究中，我们将评估吸烟的影响， 精神分裂症患者在认知测试中的禁欲， 包括神经心理学测试（WCST、SCWT、CPT、WSPT、VSWM）和PPI。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 接受整夜戒烟，然后重复测试，然后 恢复吸烟后的后续测试。一组精神分裂症患者（n=25）， 健康（n=25）非吸烟者将作为对照，并完成相同的 测试的顺序。我们还将评估高亲和力烟碱酸在 乙酰胆碱受体（nAChR），使用nAChR拮抗剂预处理 美加明（0.0、5.0和10.0 mg/天），在介导香烟的作用中 吸烟对这些认知评估的影响因此，这些研究可以提供 关于吸烟改变认知功能的机制的数据， 精神分裂症与对照吸烟者，并提出新的治疗方法， 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.