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Tumors Trigger Cancer Blues

It's no surprise that a life-threatening disease such as cancer can make you depressed. But what if tumors themselves are causing the depression? That's what a new study in rats suggests. Animals with breast tumors showed depressivelike behaviors and anxiety even though, unlike humans, they weren't aware of the psychological burden that comes with serious illness.

Up to 60% of women with breast cancer also have depression, and that figure generally holds true for other cancers. In addition to the worry and fear, a few studies suggest that treatments like chemotherapy can trigger an inflammatory cascade that's linked to depression, social isolation, and related symptoms. But no one had focused on the impact of tumors themselves for one very simple reason: It's hard to tease apart the psychological burden of cancer, the effects of treatment, and the biochemical effects of the disease.

So Leah Pyter, a behavioral neuroscientist at the University of Chicago, Illinois, turned to rats, which don't share our mental burden of being diagnosed with cancer. Working with her mentor, systems biologist Brian Prendergast, and their colleagues, Pyter induced mammary tumors in rats and then put 12 of the ailing animals, along with 12 healthy controls, through various tests that indicate depressive behaviors. In one standard test, rats placed in a cylinder of water were considered more depressed if they devoted more time to floating, as opposed to paddling. In another, researchers tallied how much sucrose the rats consumed. (Eating less suggests that the animals are down in the dumps.) The team also looked at anxiety: Rats who buried more marbles were considered more obsessive-compulsive--and thus more anxious.

The rats with tumors were more likely to display depressive behaviors and anxiety, the team reports online this week in the Proceedings of the National Academy of Sciences. For example, rats with tumors spent about 80% of their time floating in the water, compared with about 50% for healthy rats.

To pin down what caused the animals' low spirits, the researchers measured levels of cytokines, signaling molecules that can be released by tumors or by the immune cells battling them. Sick animals showed higher levels in the blood and in the hippocampus of the brain, which regulates emotional behavior. “Cytokines in the brain can induce depressivelike behaviors," says Pyter. Levels of some cytokines were more than double normal levels, the group reports. The rats with tumors also had an impaired stress response, producing less glucocorticoids, naturally occurring hormones that damp down inflammation and can suppress cytokines. Why glucocorticoid release is impaired she doesn't know, but there are scattered reports of the same effect in people with cancer.

"There really hasn't been a research focus in this area, [and] I think it's becoming increasingly important," says Charles Cleeland, a psychopharmacologist at M. D. Anderson Cancer Center in Houston, Texas, who has examined the link between chemotherapy and depression. He also notes that "some patients come to the clinical treatment with behavioral changes," backing the results found here.