Isadora Botwinick

Scientific Abstract Pancreatic cancer patients frequently present with a history of depression; often newonset depressive symptoms precede the diagnosis of cancer. These patterns of psychiatric symptoms, arising prior to cancer diagnosis, suggest that the pathophysiology of depression in pancreatic cancer may result from biological changes, such as alterations in cytokine levels, that are induced by the presence of the tumor itself. One proposed mechanism for cytokine-induced depression involves alterations in tryptophan catabolism as mediated by the enzyme IDO. Tryptophan is required for the production of the neurotransmitter serotonin; decreased serotonin levels are thought to contribute to depressive symptoms. Tryptophan is also the substrate for neurotoxic metabolites such as quinolinic acid, produced via the kynurenine pathway. Current pancreatic cancer research suggests that tumor-expressed IDO facilitates the creation of an immunotolerant environment, permissive to tumor growth and metastasis. Another effect of increased IDO expression is decreased production of serotonin and increased production of kynurenines, including quinolinic acid; both decreases in serotonin production and increased production of neurotoxic metabolites could cause depressive symptoms. Our study will explore the correlation between patient’s mood symptoms, as assessed by questionnaire, and levels of serum IDO activity, before and after surgery, ie. where the patient’s tumor burden is reduced through resection. We will also study the correlation between tumor burden (tumor stage and percent positive lymph nodes) and IDO activity level.