Relationship of Cytokines to Cognitive Functions in HCV

应聘者描述(由申请人提供)：应聘者是一名董事会认证的临床神经心理学家，有研究慢性丙型肝炎患者认知功能的经验。研究环境包括充足的办公室和实验室空间、计算机和测试设备、行政和技术人员，以及强大的机构支持，在进行以患者为中心的研究时将至少75%的时间用于职业发展。这项申请的目的是为候选人提供必要的病毒神经免疫学培训，以成为能够调查免疫反应和认知功能之间关系的独立研究人员。职业发展将包括病毒神经免疫学和与细胞因子测量相关的研究方法方面的授课和实践培训。候选人的长期目标是开发一套程序性的研究路线，这将有助于对免疫系统如何影响认知功能的有限理解。该项目的具体目标是：1)测试促炎症细胞因子干扰素-α水平升高与神经心理测试测量的慢性丙型肝炎患者认知功能障碍有关的假设，以及2)测试通过图像引导、机器人定位的经颅磁刺激表面肌电图(irTMS-SEMG)测量的慢性丙型肝炎患者的复杂运动通路抑制表明，干扰素-α水平升高与认知功能障碍相关的假设。CMC感染与严重的发病率和死亡率有关，包括情绪和认知障碍。让事情更复杂的是，干扰素-a是慢性丙型肝炎的主要治疗方法，也与情绪和认知障碍有关。虽然许多研究都集中在与干扰素-a疗法相关的情绪障碍上，但对相关的认知障碍的关注要少得多。在这项研究中，慢性丙型肝炎患者将在开始接受干扰素治疗的1个月内和接受干扰素治疗12周后再次接受神经心理测试、精神评估、细胞因子测量和irTMS-sEMG。认知功能随时间的变化将与在相同时间间隔内测试的健康对照组的变化进行比较。还将检测血清中干扰素-a和其他细胞因子的水平，并将其与认知功能有关。通过研究这些关系获得的知识将增加对免疫反应如何影响慢性丙型肝炎患者思维能力的理解，并可能为思维问题的治疗提供见解。此外，这些关系可能适用于患有其他影响思维的慢性疾病的患者，如阿尔茨海默病和系统性红斑狼疮，这也导致了对这些患者的可能治疗。

DESCRIPTION (provided by applicant): The candidate is a board certified clinical neuropsychologist with prior research experience examining cognitive functioning of patients with chronic hepatitis C. The research environment includes ample office and laboratory space, computers and testing equipment, administrative and technical personnel, and strong institutional support for devoting at least 75% time to career development in conducting patient-oriented research. The purpose of this application is to provide the candidate with the necessary training in viral neuroimmunology to become an independent researcher capable of investigating the relationship between the immune response and cognitive functioning. Career development will include both didactic and "hands on" training in viral neuroimmunology and research methodology associated with measurement of cytokines. The long-term goal is for the candidate to develop a programmatic line of research that will contribute to the limited understanding of how the immune system influences cognitive functioning. Specific Aims of this project are: 1) to test the hypothesis that higher levels of interferon-alpha (IFN-a), a proinflammatory cytokine, are associated with cognitive dysfunction in patients with chronic hepatitis C infection (CMC) as measured by neuropsychological tests, and 2) to test the hypothesis that higher levels of IFN-a are associated with cognitive dysfunction as indicated by inhibition of complex motor pathways in patients with CMC measured by image-guided, robotically positioned transcranial magnetic stimulation surface electromyography (irTMS-sEMG). CMC infection is associated with significant morbidity and mortality, including mood and cognitive disturbances. To complicate matters further, IFN-a, the primary treatment for CHC, also is associated with mood and cognitive disturbances. While much research has focused on mood disturbances associated with IFN-a therapy, far less attention has been paid to associated cognitive difficulties. In this study, patients with CHC will undergo neuropsychological testing, psychiatric assessment, cytokine measurement, and irTMS-sEMG within 1 month of beginning IFN-a therapy and again after 12 weeks of IFN-a therapy. Changes in cognitive functioning over time will be compared to that of a healthy comparison group tested over the same time interval. Levels of IFN-a and other cytokines in serum also will be examined and related to cognitive functioning. Knowledge gained by examining these relationships will increase understanding of how the immune response affects thinking abilities of patients with CHC and may provide insights into treatments for thinking problems. Additionally, these relationships may be true in patients with other chronic diseases that affect thinking, such as Alzheimer's disease and systemic lupus erythematosus, leading to possible treatments for these patients, as well.