Depression Antidepressants and HIV infectivity

抑郁症、抗抑郁药和艾滋病毒感染性 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致残原因。越来越多的研究表明 抑郁症是导致多种人类疾病发病率和死亡率的潜在风险因素， 包括艾滋病毒/艾滋病。尽管抑郁症影响HIV疾病的潜在免疫机制 进展和死亡率仍有待确定，大量证据表明杀手淋巴细胞起着关键作用。 在调节艾滋病毒感染中的作用，并在抑郁症中发生变化。在我们对抑郁症患者的研究中， 此外，在医学上健康的情况下，我们发现与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，我们已经表明抑郁症与NK细胞溶解能力的减少有关 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 与恢复HIV中NK细胞的杀伤活性有关，我们发现体外治疗淋巴细胞 SSRI可增强NK细胞的杀伤活性。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。建议对抑郁的、艾滋病毒血清阴性的人进行的研究是 旨在测试抑郁症是否与非细胞溶解、趋化因子和细胞因子、功能改变有关 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5-羟色胺和糖皮质激素(GC)的作用。 巨噬细胞和T细胞HIV受体在接触SSRI和GC拮抗剂前后的反应。 以前关于抑郁症和HIV的研究主要集中在杀手淋巴细胞的细胞溶解功能上。一种独特的力量 建议研究的重点是非细胞溶解功能以及抑郁和抗抑郁的作用。 镇静剂对这些因素具有抑制HIV的活性。因此，拟议的研究旨在 确定抑郁是否会增加对艾滋病毒感染性的易感性，以确定抗抑郁药物是否会降低 对艾滋病毒感染性的敏感性，并确定可能导致对艾滋病毒易感性的特定艾滋病毒抑制因素 抑郁症中艾滋病毒的传染性。这项研究也可能有助于确定是否有必要进行抗抑郁药物临床试验 抑郁的艾滋病毒感染者，以加强临床管理，改善艾滋病的发病率和死亡率 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 人类多种疾病发病率和死亡率的风险因素，包括 艾滋病毒/艾滋病。这项拟议的研究旨在确定抑郁症是否会增加 对艾滋病毒传染性的敏感性，以确定抗抑郁药是否会降低 对艾滋病毒感染性的易感性，并确定特定的艾滋病毒抑制因素 可能是抑郁症对艾滋病毒传染性易感性的基础。

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.