Depression, Cytokines, and Pancreatic Cancer

描述(由申请人提供)：临床抑郁症(严重抑郁综合征)发生在高达50%的胰腺癌患者中，并且明显比其他癌症更常见。越来越多的证据表明，内源性细胞因子，特别是白介素1(IL-1)、白介素6(IL-6)和肿瘤坏死因子α(TNF-α)在内科疾病(包括癌症患者)抑郁的发生中可能起着作用。同样的细胞因子在胰腺癌患者中也会升高。这项初步研究的主要目的是探讨特定的内源性细胞因子(IL-1、IL-6、肿瘤坏死因子-α)在胰腺癌患者发生严重抑郁综合征(MDS)中的作用。为了达到我们的目标，我们将使用横断面设计在4个患者样本中检验血清细胞因子(IL-1、IL-6、TNF-α)与临床抑郁(即MDS)之间的关系：a)有DSM-IV诊断为MDS的胰腺癌患者(N=25)；b)没有DSM-IV诊断的MDS的胰腺癌患者(N=25)；c)有DSM-IV诊断的MDS的健康对照组(N=25)；以及d)没有DSM-IV诊断的MDS的健康对照组(N=25)。措施将包括针对严重抑郁综合征的DSM-IV诊断(SCID)的结构性临床访谈，以及抑郁症状严重程度、疲劳严重程度、注意力和注意力以及认知功能的测量。内源性细胞因子(IL-1、IL-6、肿瘤坏死因子-α)的血浆浓度将使用标准检测方法进行测量。我们的具体目标是：1)初步检测胰腺癌患者和健康对照组血浆内源性细胞因子(IL-1、11-6、TNF-α)浓度与DSM-IV诊断MDS的关系；2)探讨胰腺癌抑郁患者和健康对照组血浆内源性细胞因子(11-1、11-6、TNF-α)浓度与抑郁症状的现象学和严重程度、疲劳的存在和严重程度、注意力、注意力和认知障碍程度的关系。这项先导性研究的结果将被用于为NIH寻求资金，用于研究细胞因子在胰腺癌患者抑郁中的作用，以及利用特定的细胞因子拮抗剂和/或COX-2抑制剂作为抗抑郁药物治疗的辅助药物治疗胰腺癌患者临床抑郁的临床干预试验。

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.