RELATIONSHIP OF CYTOKINES TO COGNITIVE FUNCTIONS IN HEPATITIS C

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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.