HIV in Women: Depression and Immunity

描述（由申请人提供）：自艾滋病开始流行以来，精神疾病一直与艾滋病毒疾病有关。迄今为止，大多数临床文献都集中在艾滋病毒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岁妇女死亡的主要原因之一，但关于感染艾滋病毒的妇女中精神疾病流行率的数据很少。艾滋病毒也是这一年龄组非裔美国妇女死亡的主要原因。我们发现，HIV阳性女性患重度抑郁症的比例是HIV血清阴性女性的四倍。严重抑郁症的高发病率，加上最近迄今为止最大规模的流行病学研究表明，抑郁症与艾滋病毒感染妇女的死亡率增加有关，强调需要进行研究，以确定艾滋病毒感染妇女的严重抑郁症、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HIV感染男性的研究中，我们发现了与抑郁相关的免疫细胞毒性细胞的改变，这表明杀伤淋巴细胞可能介导抑郁对HIV疾病进展的影响。虽然以前的研究几乎只关注艾滋病毒感染的男性，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，以及活化的CD8淋巴细胞和病毒载量的增加。拟议的对艾滋病毒血清阳性妇女的研究，主要是少数民族代表，旨在提供以下重要信息：1)抑郁症影响艾滋病毒-1复制从而影响艾滋病毒疾病进展的潜在免疫机制；2)抑郁症影响免疫和HIV疾病进展的三种潜在作用机制。本研究还可能有助于确定传统抗抑郁药（SSRIs）和新型抗抑郁药物疗法（P物质拮抗剂和糖皮质激素拮抗剂）是否对HIV感染者有益，并延长HIV感染者的生存期。

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.