Depression, Cytokines, and Pancreatic Cancer

描述（由申请人提供）：临床抑郁症（重度抑郁综合征）发生在高达50%的胰腺癌患者中，并且比其他癌症明显更常见。越来越多的证据表明，内源性细胞因子，特别是白细胞介素-1（IL-1），白细胞介素-6（IL-6）和肿瘤坏死因子α（TNF-α），在医学疾病，包括癌症患者的抑郁症的发展中的潜在作用。已经注意到这些相同的细胞因子在胰腺癌患者中升高。这项初步研究的主要目的是研究特定的内源性细胞因子（IL-1，IL-6，TNF-α）在胰腺癌患者发生重度抑郁综合征（MDS）中的作用。为了实现我们的目标，我们将研究血清细胞因子之间的关系，（IL-1、IL-6、TNF-α）与临床抑郁症（即MDS）在4个患者样本中利用横断面设计：a）具有MDS的DSM-IV诊断的胰腺癌患者（N=25）; B）没有MDS的DSM-IV诊断的胰腺癌患者（N=25）; d）没有MDS的DSM-IV诊断的健康对照（N = 25）。测量将包括DSM-IV诊断（SCID）的结构性临床访谈，以及抑郁症状严重程度，疲劳程度，注意力和集中度以及认知功能的测量。将使用标准测定法测量内源性细胞因子（IL-1、IL-6、TNF-α）的血浆浓度。我们的具体目标是：1）初步研究血浆内源性细胞因子浓度与肿瘤坏死因子的关系。（IL-1，11-6，TNF-α）和胰腺癌患者和健康对照中MDS的DSM-IV诊断; 2）探讨血浆内源性细胞因子浓度与脑梗死的关系（11-1，11-6，TNF-α）和抑郁症状的现象学和严重程度，疲劳的存在和严重程度，以及注意力、集中力和认知的损害程度，在患有胰腺癌的抑郁症患者和健康的抑郁症对照组中。这项初步研究的结果将用于寻求NIH资助，用于更大的、多机构的研究，研究细胞因子在胰腺癌患者抑郁症中的作用，以及利用特异性细胞因子拮抗剂和/或考克斯-2抑制剂作为抗抑郁药物治疗的替代物治疗胰腺癌患者临床抑郁症的临床干预试验。

DESCRIPTION (provided by applicant): Clinical Depression (Major Depressive Syndrome) occurs in up to 50% of patients with pancreatic cancer, and is significantly more common than in other cancers. Accumulating evidence suggests a potential role for endogenous cytokines, specifically interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), in the development of depression in the medically ill, including cancer patients. These same cytokines have been noted to be elevated in pancreas cancer patients. The main goal of this pilot study is to examine the role of specific endogenous cytokines (IL-1, IL-6, TNF-alpha) in the development of Major Depressive Syndrome (MDS) in patients with pancreatic cancer. To achieve our goal, we will examine the relationships between serum cytokines (IL-1, IL-6, TNF-alpha) and clinical depression (i.e. MDS) utilizing a cross sectional design in 4 samples of patients: a) Pancreas cancer patients with a DSM-IV diagnosis of MDS (N=25); b) Pancreas cancer patients without a DSM-IV diagnosis of MDS (N=25); c) Healthy Controls with a DSM-IV diagnosis of MDS (N=25); and d) Healthy Controls without a DSM-IV diagnosis of MDS (N=25). Measures will include a structural clinical interview for DSM-IV diagnosis (SCID) of Major Depressive Syndrome, as well as measures of depressive symptom severity, fatigue severity, concentration and attention, and cognitive function. Plasma concentrations of endogenous cytokines ((IL-1, IL-6, TNF-alpha) will be measured utilizing standard assays. Our specific aims are: 1) To, preliminarily, examine the relationships between plasma concentrations of endogenous cytokines (IL-1, 11-6,TNF-alpha) and a DSM-IV diagnosis of MDS in patients with pancreas cancer and healthy controls; 2) To explore the relationships between plasma concentrations of endogenous cytokines (11-1, 11-6,TNF-alpha) and the phenomenology and severity of depressive symptoms, presence and severity of fatigue, and degree of impairment in attention, concentration and cognition, in depressed patients with pancreas cancer and healthy depressed controls. The results of this pilot study will be utilized to seek NIH funding for larger, multi-institutional, studies examining the role of cytokines in depression in pancreas cancer patients, as well as clinical intervention trials for the treatment of clinical depression in pancreas cancer patients that utilize specific cytokine antagonists and/or COX-2 inhibitors as adjuncts to antidepressant drug therapy.