Neuroinflammation and Modulating Factors in Depression and HIV

项目概要/摘要 艾滋病毒感染者的抑郁症与更差的艾滋病毒结果相关，包括更差的护理，药物治疗 坚持和保持护理。抑郁症在艾滋病毒感染者中的流行率也是在艾滋病毒感染者中的三倍。 一般人口。虽然有复杂的原因，包括心理社会，有越来越多的机构， 有证据表明，炎症与包括抑郁症在内的精神疾病有关， 艾滋病毒感染者的病理生理学还不清楚。更好地了解发病机制将 帮助发现新的治疗方法。更好的抑郁症治疗可能因此导致参与/保留护理 以及更好的艾滋病毒结果，包括病毒学控制。更好地控制艾滋病毒将有助于实现艾滋病规划署90/90/90 目标是诊断90%的艾滋病毒阳性者，为90%的确诊者提供抗逆转录病毒治疗， 90%的治疗者抑制。 这个K23奖项的具体目的是：1）确定CSF炎症和神经元损伤是否是 2）确定26岁时抑郁症的患病率 团体心理治疗和抗抑郁药物治疗的效果优于抗抑郁药物治疗 单独使用药物，并确定抑郁症的持续性是否与更高水平的先天性 由于全身性应激反应引起的炎症。我假设抑郁症与 HIV感染者CSF中先天性炎症信号失调。我还假设在艾滋病毒中- 感染了CD 4 <200个细胞/mL和抑郁症的乌干达人开始接受艾滋病毒治疗， 抑郁症在26周的人相比，血浆白细胞介素-6和皮质醇增加， 抑郁症解决。我进一步假设，每周一次的团体心理治疗会减少抑郁症的发生。 症状，在HIV治疗26周时通过患者健康问卷-9（PHQ-9）测量。 Lofgren博士的长期职业目标是成为一名独立的翻译研究人员， 心理健康和免疫学之间的差距，将基础科学概念转移到资源的临床应用- 有限的设置。在迄今为止的培训期间，Lofgren博士花了三年时间进行临床研究， 东非，过去两年都在明尼苏达州和乌干达的坎帕拉之间。K23奖项 将提供指导的职业发展，使用课程的组合，以补充目前的 知识差距和实际指导研究经验，以建立研究技能的坚实基础， 心理健康免疫学和神经科学这将使她成为心理神经免疫学的专家。 该奖项将建立在现有的国际合作基础上，允许候选人应用她的K23培训 在患有抑郁症和晚期艾滋病毒/艾滋病的人中进行临床和转化研究， CD 4 <200个细胞/μ L。

PROJECT SUMMARY/ABSTRACT Depression in HIV is associated with worse HIV outcomes including worse engagement in care, medication adherence, and retention in care. Depression is also three times more prevalent in those with HIV than in the general population. While there are complex reasons including psychosocial, there is a growing body of evidence that inflammation is linked to mental illness including depression although the underlying pathophysiology in people living with HIV is not well understood. Better understanding of the pathogenesis will help identify new treatments. Better depression treatments may thereby lead to engagement/retention in care and better HIV outcomes including virologic control. Better HIV control will help achieve the UNAIDS 90/90/90 goals to diagnose 90% of all HIV-positive persons, provide ART for 90% of those diagnosed, and achieve viral suppression for 90% of those treated. The Specific Aims of this K23 award are: 1) To determine if CSF inflammation and neuronal damage are associated with depression in HIV-infected Ugandans and 2) Determine if the prevalence of depression at 26 weeks of HIV therapy is improved with group psychotherapy and antidepressant medicine over antidepressant medicine alone and determine if the persistence of depression is associated with higher levels of innate inflammation due to the systemic stress response. I hypothesize that depression is associated with dysregulated innate inflammatory signaling in CSF in HIV-infected persons. I also hypothesize that in HIV- infected Ugandans with CD4 <200 cells/L and depression initiating HIV therapy, those with persisting depression at 26 weeks will have increased plasma interleukin-6 and cortisol compared to persons whose depression resolves. I further hypothesize that structured weekly group psychotherapy will reduce depressive symptoms, measured by patient health questionnaire-9 (PHQ-9) at 26 weeks of HIV therapy. Dr. Lofgren’s long-term career goal is to become an independent translational researcher who bridges the gap between mental health and immunology, moving basic science concepts to clinical application in resource- limited settings. During her training to date, Dr. Lofgren has spent three years performing clinical research in East Africa, and all of the last two years divided between Minnesota and Kampala, Uganda. This K23 award will provide for mentored career development using a combination of coursework to supplement current knowledge gaps and practical mentored-research experience to build a strong foundation of research skills in mental health, immunology and neuroscience. This will allow her to be an expert in psychoneuroimmunology. The award will build upon existing international collaborations allowing the candidate to apply her K23 training into clinical and translational research among persons living with depression and advanced HIV/AIDS with CD4<200 cells/L.