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 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.
