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

• 批准号: 9980508
• 负责人: SARAH LOFGREN
• 金额: $ 19.86万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 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/9980508
• 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; 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; 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; 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

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.

项目摘要/摘要 艾滋病毒中的抑郁症与艾滋病毒的恶心结果有关 依从性和保留率。抑郁症在艾滋病毒患者中也比在 一般人口。虽然有复杂的理由包括社会心理，但越来越多 炎症与精神疾病有关的证据，包括抑郁症，尽管基础 艾滋病毒患者的病理生理学尚不清楚。更好地理解发病机理将 帮助确定新的治疗方法。更好的抑郁疗法可能会导致参与/保留护理 以及更好的HIV结果，包括病毒学控制。更好的艾滋病毒控制将有助于实现UNAID 90/90/90 诊断所有艾滋病毒阳性的人的90％的目标，为90％的被诊断者提供艺术，并获得病毒 抑制90％接受治疗的人。 该K23奖的具体目的是：1）确定CSF炎症和神经元损害是否为 与艾滋病毒感染的乌干达人的抑郁症相关，2）确定抑郁症的患病率是否在26 抗抑郁药的组心理治疗和抗抑郁药可改善艾滋病毒治疗数周 仅医药并确定抑郁症的持久性是否与较高的先天性有关 由于全身应力反应引起的炎症。我假设抑郁症与 艾滋病毒感染者中CSF​​中的先天炎症信号失调。我还假设在艾滋病毒中 用CD4 <200细胞/L和抑郁症感染的乌干达人启动HIV治疗 与患者相比 抑郁症可以解决。我进一步假设结构化的每周小组心理治疗将减轻抑郁症 症状，在HIV治疗26周时通过患者健康调查表（PH​​Q-9）测量。 Lofgren博士的长期职业目标是成为一名独立翻译的研究人员，他桥接 心理健康与免疫学之间的差距，将基础科学概念转移到资源中的临床应用 - 有限的设置。迄今为止，在培训期间，Lofgren博士花了三年的时间进行临床研究 东非，过去两年在明尼苏达州和乌干达的坎帕拉之间分裂。这个K23奖 将使用课程的组合来补充当前 知识差距和实践指导的研究经验，以建立强大的研究技能基础 心理健康，免疫学和神经科学。这将使她成为心理肌免疫学专家。 该奖项将基于现有的国际合作，使候选人可以进行她的K23培训 参与抑郁症患者和高级艾滋病毒/艾滋病的临床和翻译研究 CD4 <200细胞/L。