Neuroinflammation and Modulating Factors in Depression and HIV

项目摘要/摘要 HIV患者的抑郁与较差的HIV结局相关，包括较差的护理、用药 坚持不懈，并保持在关怀中。在艾滋病毒携带者中，抑郁症的患病率也是艾滋病患者的三倍 普通人口。虽然有包括心理社会在内的复杂原因，但有越来越多的人 炎症与包括抑郁症在内的精神疾病有关的证据，尽管潜在的 艾滋病毒携带者的病理生理学还不是很清楚。对发病机制的更好理解将 帮助确定新的治疗方法。因此，更好的抑郁症治疗可能会导致敬业/留住护理 以及更好的艾滋病毒结果，包括病毒学控制。更好的艾滋病毒控制将有助于实现联合国艾滋病规划署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，并实现病毒传播 90%的接受治疗的人会受到抑制。 这个K23奖项的具体目的是：1)确定脑脊液炎症和神经元损伤是否 与感染艾滋病毒的乌干达人的抑郁症有关，以及2)确定26岁时抑郁症的患病率 与抗抑郁药相比，团体心理治疗和抗抑郁药改善了为期数周的艾滋病毒治疗 并确定抑郁症的持续性是否与更高水平的先天激素有关 全身应激反应引起的炎症。我假设抑郁症与 HIV感染者脑脊液中先天炎症信号的失调。我还假设在HIV病毒中- 感染CD4200Cells/的乌干达人L和抑郁症启动艾滋病毒治疗，那些持续的 与那些在26周时抑郁的人相比，26周时抑郁的人血浆白介素6和皮质醇水平会升高 抑郁症就解决了。我进一步假设，每周有组织的集体心理治疗将减少抑郁 在HIV治疗26周时用患者健康问卷-9(PHQ-9)测量症状。 洛夫格伦博士的长期职业目标是成为一名独立的翻译研究员，在 心理健康和免疫学之间的差距，将基础科学概念转移到临床应用资源- 有限的设置。在到目前为止的培训期间，洛夫格伦博士花了三年时间进行临床研究 东非，过去两年一直在明尼苏达州和乌干达的坎帕拉之间奔波。本次K23大奖 将提供辅导式职业发展，使用课程作业的组合来补充现有的 知识差距和实际指导研究经验，为研究技能奠定坚实的基础 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 在抑郁症和晚期艾滋病毒/艾滋病患者中进行临床和翻译研究 200cell/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.