Depression Antidepressants and HIV infectivity

抑郁症 抗抑郁药和 HIV 感染

• 批准号: 8242066
• 负责人: DWIGHT L. EVANS
• 金额: $ 63.43万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-24 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8242066
• 关键词: AIDS/HIV problem; Address; Affect; Antidepressive Agents; Antiviral Agents; CCL3 gene; CCL4 gene; CCR5 gene; CD4 Antigens; CD8-Positive T-Lymphocytes; CD8B1 gene; CXCR4 gene; Cardiovascular Diseases; Cell physiology; Cells; Cellular Immunity; Clinical; Clinical Management; Clinical Research; Clinical Trials; Communicable Diseases; Coupled; Depressed mood; Diabetes Mellitus; Disease; Disease Progression; Exposure to; Glucocorticoids; HIV; HIV Infections; HIV Receptors; Immune; Individual; Investigation; Lymphocyte; Lymphocyte Function; Malignant Neoplasms; Measures; Mediating; Medical; Mental Depression; Morbidity - disease rate; Natural Immunity; Natural Killer Cells; Pathway interactions; Peripheral Blood Mononuclear Cell; Play; Population; Predisposition; Prospective Studies; Publishing; RANTES; Resolution; Risk Factors; Role; Selective Serotonin Reuptake Inhibitor; Series; Serotonin; Severities; Stress; System; T-Cell Receptor; T-Lymphocyte; TNF gene; Testing; Woman; World Health Organization; abstracting; chemokine; chemokine receptor; cytokine; cytotoxicity; depressive symptoms; design; disability; disability-adjusted life years; epidemiology study; human disease; improved; macrophage; men; monocyte; mortality; receptor; receptor sensitivity; research study; response; restoration

Depression, Antidepressants, and HIV-Infectivity Abstract The medical burden of depression is increasing and the World Health Organization projects that by the year 2020, depression will be the second leading cause of disability worldwide. An increasing number of studies have implicated depression as a potential risk factor in the morbidity and mortality for a wide range of human diseases, including HIV/AIDS. Although the underlying immune mechanisms by which depression influences HIV disease progression and mortality remain to be determined, considerable evidence suggests that killer lymphocytes play key roles in regulating HIV infection and are altered in depression. In our studies of individuals who are depressed, but otherwise medically healthy, we have found depression-associated decreases in natural killer (NK) cytolytic activity. In studies of HIV-infected individuals, we have shown that depression is associated with a reduction in NK cytolytic activity and an increase in HIV disease progression. We have recently demonstrated that resolution of depression is associated with restoration of NK cytotoxicity in HIV, and we have found that ex vivo treatment of lymphocytes with an SSRI enhances NK cytolytic activity. We have also observed that an SSRI and a glucocorticoid antagonist inhibit HIV infectivity of macrophages in HIV. The proposed study of depressed, HIV-seronegative individuals is designed to test whether depression is associated with non-cytolytic, chemokine and cytokine, functional alterations of killer lymphocytes, as well as chemokine receptor sensitivity of macrophages and T-cells that are relevant to HIV- infectivity. We will study the role of serotonin and glucocorticoids (GCs) by comparing killer lymphocyte function in macrophage and T-cell HIV receptor response before and after exposure to an SSRI and a GC antagonist. Previous studies of depression and HIV have focused on cytolytic function of killer lymphocytes. A unique strength of the proposed study is the emphasis on the non-cytolytic functions and the effects of depression and anti- depressants on these factors which have HIV suppressive activity. Thus, the proposed study is designed to determine if depression increases the susceptibility to HIV-infectivity, to determine if anti-depressants decrease the susceptibility to HIV-infectivity, and to determine specific HIV suppressive factors that may underlie susceptibility to HIV-infectivity in depression. This study also may help determine if anti-depressant clinical trials are warranted in depressed HIV-infected individuals in order to enhance clinical management and improve morbidity and mortality of HIV infection. -1a- The medical burden of depression is increasing and the World Health Organization projects that by the year 2020, depression will be the second leading cause of disability worldwide. An increasing number of studies have implicated depression as a potential risk factor in the morbidity and mortality for a wide range of human diseases, including HIV/AIDS. The proposed study is designed to determine if depression increases the susceptibility to HIV-infectivity, to determine if anti-depressants decrease the susceptibility to HIV-infectivity, and to determine specific HIV suppressive factors that may underlie susceptibility to HIV-infectivity in depression.

抑郁症、抗抑郁药和艾滋病毒感染 抽象的 抑郁症的医疗负担正在增加，世界卫生组织预计到 2020 年， 抑郁症将成为全球第二大残疾原因。越来越多的研究表明 表明抑郁症是多种人类疾病发病率和死亡率的潜在危险因素， 包括艾滋病毒/艾滋病。尽管抑郁症影响艾滋病毒疾病的潜在免疫机制 进展和死亡率仍有待确定，大量证据表明杀伤淋巴细胞发挥关键作用 调节 HIV 感染的作用在抑郁症中发生改变。在我们对抑郁症患者的研究中， 在其他方面健康的情况下，我们发现与抑郁症相关的自然杀伤细胞（NK）细胞溶解活性降低。 在对 HIV 感染者的研究中，我们发现抑郁症与 NK 细胞溶解能力的降低有关。 活动和艾滋病毒疾病进展的增加。我们最近证明抑郁症的解决 与 HIV 中 NK 细胞毒性的恢复有关，我们发现淋巴细胞的离体治疗 与 SSRI 结合可增强 NK 细胞溶解活性。我们还观察到 SSRI 和糖皮质激素拮抗剂 抑制HIV巨噬细胞的HIV感染性。拟议的针对抑郁症、艾滋病毒血清阴性个体的研究是 旨在测试抑郁症是否与非细胞溶解、趋化因子和细胞因子、功能改变相关 杀伤淋巴细胞的敏感性，以及与 HIV 相关的巨噬细胞和 T 细胞的趋化因子受体敏感性 传染性。我们将通过比较杀伤淋巴细胞的功能来研究血清素和糖皮质激素 (GC) 的作用 暴露于 SSRI 和 GC 拮抗剂前后的巨噬细胞和 T 细胞 HIV 受体反应。 先前对抑郁症和艾滋病毒的研究主要集中在杀伤淋巴细胞的溶细胞功能上。独特的实力 拟议研究的重点是非细胞溶解功能以及抑郁症和抗抑郁症的影响 对这些因素有抑制作用的抑制剂。因此，拟议的研究旨在 确定抑郁症是否会增加艾滋病毒感染的易感性，确定抗抑郁药是否会降低艾滋病毒感染的可能性 HIV 感染的易感性，并确定可能导致易感性的特定 HIV 抑制因素 抑郁症中的艾滋病毒感染性。这项研究还可能有助于确定是否有必要进行抗抑郁临床试验 抑制艾滋病毒感染者的情绪，以加强临床管理并改善其发病率和死亡率 艾滋病毒感染。 -1a- 抑郁症的医疗负担正在增加，世界卫生组织 预计到 2020 年，抑郁症将成为导致残疾的第二大原因 全世界。越来越多的研究表明抑郁症是一种潜在的 多种人类疾病发病率和死亡率的危险因素，包括 艾滋病毒/艾滋病。拟议的研究旨在确定抑郁症是否会增加 对艾滋病毒感染的易感性，以确定抗抑郁药是否会降低 对 HIV 感染的易感性，并确定特定的 HIV 抑制因素 可能是抑郁症患者对艾滋病毒感染易感性的基础。