RELATIONSHIP OF CYTOKINES TO COGNITIVE FUNCTIONS IN HEPATITIS C

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 目的：本研究的中心假设是IFN-α是CHC患者认知功能障碍的关键决定因素。 将通过以下两个具体目标来检验这一假设： 具体目标1：通过神经心理学测试，验证CHC患者血清中较高水平的IFN-α与认知功能障碍相关的假设。 具体目标二：通过神经影像学检查，验证血清中较高水平的IFN-α与额叶皮层下网络异常相关的假设。 研究设计：这是一项前瞻性、重复测量的研究设计，涉及40名CHC患者和20名健康对照（HC）参与者。 开始使用IFN-α进行抗病毒治疗的CHC患者将在基线（首次治疗后1个月内）、治疗12周、24周和48周后以及治疗停止后6个月（无论何时停止）进行评估。 HC受试者将在相同的时间间隔接受与CHC患者相同的评估。 方法：尿液毒理学筛查、细胞因子测定、精神病评估（SCID-I）、神经心理学评估（注意力-执行功能、信息处理/精神障碍、学习/记忆、努力和心理困扰）、神经影像学（MRI、高分辨率结构MRI、静息态fMRI、DTI [F]脱氧葡萄糖正电子发射断层扫描）。 临床相关性：拟议的研究从理论和患者护理的角度都有重要的影响。 获得免疫和中枢神经系统（CNS）之间的相互作用的理解可以帮助提供认知功能障碍的病因学理论在CHC，以及在其他条件下，其中免疫系统是牵连的，然后可能导致有针对性的干预措施。 初步数据表明，IFN-α在认知功能障碍的病因学中可能发挥作用，但这种关系尚未通过检查患有和不患有认知功能障碍的患者血清中IFN-α的水平进行专门研究。 此外，没有研究探讨了CHC患者的这种关系。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. OBJECTIVE: The central hypothesis of this study is that IFN-alpha is a key determinant of cognitive dysfunction observed in CHC patients. This hypothesis will be tested by addressing the following two specific aims: Specific Aim 1: To test the hypothesis that higher levels of IFN-alpha in serum are associated with cognitive dysfunction in CHC patients as measured by neuropsychological tests. Specific Aim 2: To test the hypothesis that higher levels of IFN-alpha in serum are associated with abnormalities in frontal-subcoritcal networks as measured by neuroimaging. RESEARCH PLAN: This is a prospective, repeated measures study design involving 40 CHC patients and 20 healthy control (HC) participants. CHC patients beginning antiviral therapy with IFN-alpha will be assessed at baseline (within one month of their first treatment), after 12, 24, and 48 weeks of therapy, and six months after treatment is stopped (regardless of when it was stopped). HC participants will undergo the same assessments as CHC patients at the same time intervals. METHODS: Urine toxicology screen, cytokine assays, psychiatric assessment (SCID-I), neuropsychological assessment (attention-executive functioning, information processing/psychomotor, learning/memory, effort and psychological distress), neuroimaging (MRI, high resolution structural MRI, resting-state fMRI, DTI [F]deoxyglucose positron emission tomography). CLINICAL RELEVANCE: The proposed study has important ramifications from both theoretical and patient care perspectives. Gaining understanding of interactions between the immune and central nervous system (CNS) can aid in providing etiological theories of cognitive dysfunction in CHC, as well as in other conditions in which the immune system is implicated, which then may lead to targeted interventions. Preliminary data indicate a possible role of IFN-alpha in the etiology of cognitive dysfunction, but this relationship has not been investigated specifically by examining levels of IFN-alpha in serum of patients with and without cognitive dysfunction. Further, no study has explored this relationship in patients with CHC.