Depression Antidepressants and HIV infectivity

抑郁症、抗抑郁药和HIV抵抗力 摘要 抑郁症的医疗负担正在增加，世界卫生组织预测，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 暗示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的潜在免疫机制 进展和死亡率仍有待确定，相当多的证据表明，杀伤淋巴细胞发挥关键作用， 调节HIV感染的作用，并在抑郁症中改变。在我们对抑郁症患者的研究中 在其他医学上健康的情况下，我们发现抑郁症相关的自然杀伤（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细胞溶解性降低有关。 活动和艾滋病毒疾病进展的增加。我们最近证明了抑郁症的解决方案 与HIV中NK细胞毒性的恢复有关，我们已经发现淋巴细胞的离体处理 SSRI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中巨噬细胞的HIV感染性。这项针对抑郁症、HIV血清阴性个体的研究计划， 旨在测试抑郁症是否与非细胞溶解性，趋化因子和细胞因子，功能改变有关。 以及巨噬细胞和与HIV相关的T细胞的趋化因子受体敏感性， 传染性我们将研究血清素和糖皮质激素（GC）的作用，通过比较杀伤淋巴细胞功能， 在暴露于SSRI和GC拮抗剂之前和之后的巨噬细胞和T细胞HIV受体应答。 以前关于抑郁症和HIV的研究主要集中在杀伤淋巴细胞的细胞溶解功能上。独特的力量 的非细胞溶解功能，以及抑制和抗肿瘤的作用。 抑制剂对这些具有HIV抑制活性的因素。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风险。 对HIV感染的易感性，并确定可能导致HIV感染易感性的特定HIV抑制因素， 抑郁症中的HIV感染这项研究也可能有助于确定是否有必要进行抗肿瘤临床试验， 抑郁的艾滋病毒感染者，以加强临床管理，提高发病率和死亡率， 艾滋病毒感染。 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。 国际吧越来越多的研究表明抑郁症是一种潜在的 一系列人类疾病发病率和死亡率的风险因素，包括 艾滋病毒/艾滋病的这项拟议中的研究旨在确定抑郁是否会增加 艾滋病毒感染的易感性，以确定是否抗抑郁药减少 艾滋病毒感染的易感性，并确定特定的艾滋病毒抑制因素， 可能是抑郁症患者易感染艾滋病病毒的原因。

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.