A third source connected to depression in cancer patients

Researchers in Psychology have found, for the first time, a biological link between cancerous tumors and negative mood changes that could help explain the connections between cancer and depression.

Using an animal model, the team determined that tumors produce increased quantities of substances that are associated with depression and which are transmitted to the brain. Additionally, they found that tumors disrupt pathways that normally moderate the impact of depression-causing substances.

The research further showed that tumors induce changes in gene expression in the hippocampus, the portion of the brain that regulates emotion. Although researchers have long known that depression is a common outcome for people diagnosed with cancer, they had not known if it was brought on by a patient learning of the diagnosis or the result of treatments such as chemotherapy. Now a third source may have been identified.

“Our research shows that two types of tumor-induced molecules, one secreted by the immune system and another by the stress axis, may be responsible,” said Leah Pyter, a postdoctoral fellow and lead author of “Peripheral Tumors Induce Depressive-like Behaviors and Cytokine Production and Alter Hypothalamic-Pituitary-Andrenal Axis Regulation,” a paper published in the current issue of the Proceedings of the National Academy of Sciences.

“Both of these substances have been implicated in depression, but neither has been examined over time frames and magnitudes that are characteristic of chronic diseases such as cancer,” she said.

For their research, the team conducted a series of tests on rats, some of which had cancer, to determine their behavioral responses in tests of emotional state.

“Rats are commonly used to test drugs that are being studied for potential human benefits, such as treating depression,” said Brian Prendergast, Associate Professor in Psychology and senior author of the study. “In this case, examining behavioral responses to tumors in non-human animals is particularly useful because the rats have no awareness of the disease, and thus their behavioral changes were likely the result of purely biological factors.”

Working with the rats, the team submitted them to a swimming test, a commonly used stress test that creates a condition in rats that is similar to depression in humans, and which has been used to study the effects of antidepressants. They found that the rats with tumors became less motivated to escape the swimming test. The rats with tumors also were less eager to drink sugar water, a substance that usually attracts the appetites of healthy rats.

Further tests revealed that the rats with tumors had increased levels of cytokines in their blood and in the hippocampus when compared with healthy rats. Cytokines are produced by the immune system, and an increase in cytokines has been linked to depression.

The researchers also found that the production of stress hormones, including that of corticosterone, was altered in rats with tumors. Corticosterone helps regulate the impact of cytokines, and therefore reducing its production increases the impact of cytokines.

The American Cancer Society fellowship, a National Institutes of Health grant and a Brain Research Foundation grant helped support this project.