Depression, Cytokines, and Pancreatic Cancer

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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.