Cytokine and Adrenocortical Mediation of Cancer-Induced Depression
2008 Seed Grant
Brian J. Prendergast, Ph.D.
University of Chicago
There is a strong correlation between physical illnesses and mood disorders. This relationship is particularly robust for cancer and depression; cancer patients carry a 50% risk of major depression. Clinically-speaking, cancer-associated depression is not a psychiatric issue of secondary importance: depression is associated with decreased cancer survivorship, and depressed cancer patients are three times more likely to be noncompliant with treatment protocols. Surprisingly, however, causal links between chronic peripheral diseases, such as cancer, and emotional disturbances have not been established, and have remained largely uninvestigated.
A number of chemical messengers in the body are capable of inducing depressive-like states; these signaling molecules include neurotransmitters, hormones, and cytokines. Cytokines are signaling molecules produced by cells in the immune system, but they are also secreted in into the general circulation by some types of tumors. The proposed work uses a rodent model of breast cancer to examine whether tumor-derived cytokines cause depression. Experiments will test whether tumor-derived cytokines gain access to the brain, and if so, whether they trigger changes in neural systems that regulate emotion (the limbic system) that ultimately lead to a depressive-like syndrome.
Additional experiments will examine whether cancer suppresses the activity of the endocrine stress-response system (the hypothalamic-pituitary-adrenal axis) which normally functions to inhibit cytokine signaling in the brain, thereby resulting in an amplification of the depression-inducing effects of even modest increases in cytokines. Establishing a role for cytokines or stress hormones in cancer-induced depression would have implications for cancer treatment, informing the development of therapies that target specific receptors to alleviate cancer-induced mood disorders. The work also stands to generate novel insights into immune-to-brain signaling which will increase our basic understanding of how chronic diseases affect emotions.