HIV in Women: Depression and Immunity

描述(由申请人提供)：自艾滋病流行开始以来，精神病发病率一直与艾滋病毒疾病有关。到目前为止，大多数临床文献都集中在HIV血清阳性男性的精神问题上。尽管艾滋病毒仍然是美国25岁至44岁女性死亡的主要原因之一，但关于感染艾滋病毒的女性精神障碍患病率的数据很少。艾滋病毒也是这个年龄段的非裔美国女性的主要死亡原因。我们发现，与艾滋病毒血清阴性的妇女相比，艾滋病毒阳性妇女中患有严重抑郁症的妇女比例高出四倍。这种高比例的严重抑郁症，加上最近和迄今为止最大的流行病学研究表明，抑郁症与艾滋病毒感染妇女死亡率的增加有关，这突显了需要进行研究，以确定艾滋病毒感染妇女中抑郁症、免疫力和艾滋病毒疾病进展之间的关系。抑郁症可能影响HIV疾病进展和死亡率的潜在免疫机制仍有待了解。在我们对感染HIV的男性的研究中，我们发现了与抑郁症相关的免疫细胞毒细胞的变化，这表明杀伤淋巴细胞可能介导了抑郁症对HIV疾病进展的影响。尽管之前的研究几乎完全集中在感染艾滋病毒的男性身上，但我们最近发现，患有抑郁症的女性表现出自然杀伤细胞活性的显著降低以及激活的CD8淋巴细胞和病毒载量的增加。拟议对艾滋病毒血清阳性妇女的研究主要是为了提供关于以下方面的重要信息：1)抑郁症影响HIV-1复制从而影响艾滋病毒疾病进展的潜在免疫机制；以及2)抑郁症影响免疫和艾滋病毒疾病进展的三种可能的作用机制。本研究还可能有助于确定常规抗抑郁药(SSRI)以及新型抗抑郁药物(P物质拮抗剂和糖皮质激素拮抗剂)是否可以使艾滋病毒感染者受益，并延长艾滋病毒感染患者的生存时间。

DESCRIPTION (provided by applicant): Psychiatric morbidity has been associated with HIV disease since the beginning of the AIDS epidemic. Most of the clinical literature to date has focused on psychiatric issues in men who are HIV seropositive. There has been little data regarding the prevalence of psychiatric disorders in HIV infected women, despite the fact that HIV remains among the leading causes of death for US women between the ages of 25 and 44. HIV also is the leading cause of death among African American women in this age group. We found that the proportion of women with current major depression was four times higher in HIV positive women compared to HIV seronegative women. This high rate of major depression coupled with the recent and largest epidemiology study to date indicating that depression is associated with increased mortality in HIV-infected women, underscores the need for studies to ascertain the relationship of major depression, immunity, and HIV disease progression in HIV infected women. The potential immune mechanisms by which depression may influence HIV disease progression and mortality remain to be understood. In our studies of HIV infected men, we have found depression associated alterations of immune cytotoxic cells suggesting that killer lymphocytes might mediate the effects of depression on HIV disease progression. Although previous studies have focused almost exclusively on HIV infected men, we have recently found that women with depression exhibit significant reductions in natural killer cell activity as well as increases in activated CD8 lymphocytes and viral load. The proposed study of HIV seropositive women, largely of minority representation, is designed to provide important information on 1) the underlying immune mechanisms by which depression my influence HIV-1 replication and thereby HIV disease progression; and 2) three potential mechanisms of action whereby depression my influence immunity and HIV disease progression. The present study may also help determine whether conventional antidepressants (SSRIs) as well as novel antidepressant pharmacotherapies (substance P antagonists and glucocorticoid antagonists) might benefit HIV-infected individuals and extend survival with HIV infection.