Neuroinflammation and Modulating Factors in Depression and HIV

抑郁症和艾滋病毒的神经炎症和调节因素

基本信息

批准号：
10231117
负责人：
SARAH LOFGREN
金额：
$ 19.88万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10231117
关键词：
AIDS/HIV problem Africa Antidepressive Agents Award Basic Science Behavior Therapy Behavioral Behavioral Symptoms Biological Markers Caring Chronic Disease Clinical Clinical Research Collaborations Complex Coupled Data Depressed mood Diagnosis Foundations Functional disorder General Population Goals Group Psychotherapy HIV HIV Infections HIV Seropositivity HIV therapy Hamilton Rating Scale for Depression Health Hydrocortisone Immunology Individual Inflammation Inflammatory Interleukin-6 International Intervention Knowledge L Cells Lead Light Link Longitudinal Studies Measures Medicine Mental Depression Mental Health Mental disorders Mentored Patient-Oriented Research Career Development Award Mentors Methods Minnesota Nerve Degeneration Neuraxis Neurons Neurosciences Outcome Pathogenesis Pathway interactions Patients Pattern Persons Pharmacology Study Plasma Prevalence Prospective cohort Psychoneuroimmunology Questionnaires RNA Reporting Research Research Personnel Research Project Grants Research Support Research Training Resources Role Sampling Serotonin Uptake Inhibitors Signal Transduction Structure Testing Time Training Translational Research Uganda Viral antiretroviral therapy biological adaptation to stress biomarker identification career career development clinical application cohort cytokine depressive symptoms efficacious treatment experience follow-up immune reconstitution improved innovation medication compliance mortality neurofilament neuroinflammation psychosocial responders and non-responders skills standard care translational scientist treatment adherence treatment responders treatment-resistant depression virology

项目摘要

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.

项目概要/摘要艾滋病毒感染者的抑郁症与更糟糕的艾滋病毒结果相关，包括护理、药物治疗参与度较差艾滋病毒感染者的抑郁症患病率是非感染者的三倍。尽管有复杂的心理原因（包括社会原因），但越来越多的人出现这种情况。有证据表明炎症与包括抑郁症在内的精神疾病有关，尽管潜在的艾滋病毒感染者的病理生理学尚不清楚。帮助确定新的治疗方法，从而可能导致护理的参与/保留。更好的艾滋病毒结果，包括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% 的诊断者提供抗逆转录病毒治疗，并实现病毒 90%的治疗者受到抑制。该 K23 奖项的具体目标是： 1) 确定脑脊液炎症和神经元损伤是否与与感染 HIV 的乌干达人的抑郁症相关；2) 确定 26 岁时抑郁症的患病率是否与抗抑郁药物相比，团体心理治疗和抗抑郁药物可改善艾滋病毒治疗数周的效果单独使用药物并确定抑郁症的持续存在是否与较高水平的先天性相关我认为抑郁症与全身应激反应有关。 HIV感染者脑脊液中先天炎症信号失调。 CD4 <200 个细胞/μL 且患有抑郁症的乌干达感染者开始 HIV 治疗，与患有抑郁症的人相比，第 26 周时患有抑郁症的人血浆白细胞介素 6 和皮质醇会增加。我进一步认为每周有组织的团体心理治疗会减少抑郁症。症状，在 HIV 治疗 26 周时通过患者健康问卷 9 (PHQ-9) 进行测量。 Lofgren 博士的长期职业目标是成为一名独立的转化研究员，在不同领域之间架起桥梁。心理健康和免疫学之间的差距，将基础科学概念转化为资源中的临床应用在迄今为止的培训期间，Lofgren 博士花了三年时间在有限的环境中进行临床研究。东非，过去两年的 K23 奖项在明尼苏达州和乌干达坎帕拉之间分配。将使用课程组合来补充当前的职业发展指导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、免疫学和神经科学将使她成为心理神经免疫学专家。该奖项将建立在现有的国际合作基础上，使候选人能够应用她的 K23 培训进入抑郁症和晚期艾滋病毒/艾滋病患者的临床和转化研究 CD4<200个细胞/μL。