Researchers have long known that constant stress can impair the body's ability to fight diseases such as cancer. In order to examine this idea further, researchers investigated the endocrine, immune and tumor growth–promoting mechanisms mediating the effects of anxiety and stress on tumor development.

Using two common behavioral tests that measure anxiety based on avoidance of danger, a team of scientists led by Firdaus S. Dhabhar (Stanford University, Stanford, CA) first determined which of their mice had naturally high or low anxiety, dividing them into two groups. Next, both groups of mice were repeatedly exposed to ultraviolet B (UVB) radiation, which is carcinogenic and known to cause most non-melanoma skin cancers in humans, of which there are 2–3 million cases each year worldwide. Dhabhar explained in a press release, “This skin cancer model is really valuable because it closely mimics human skin cancer.”

The mice that had showed higher anxiety on the behavioral tests grew more tumors after UVB exposure than those that had showed lower anxiety on the tests (PLoS One e33069; published online 25 April 2012). The high-anxiety mice also exhibited lower gene expression of factors that are protective against cancer, as well as higher expression of factors that are cancer-promoting, compared with the gene expression in low-anxiety mice. Furthermore, the ratio of immuno-protective to immuno-suppressive T cells in the high-anxiety mice was diminished. The highly anxious mice also had higher levels of a growth factor that is known to be associated with skin cancer in their skin, possibly underlying the increased tumor growth in these mice.

Next, the researchers wanted to determine how higher anxiety led to these physiological changes. They measured levels of corticosterone, the stress hormone, in the adrenal glands and found that high-anxiety mice had higher levels than low-anxiety mice. When the mice were restrained to induce stress, the mice that had shown higher anxiety on the earlier behavioral tests had higher levels of corticosterone in the blood than mice that had shown lower anxiety on the behavioral tests.

Long-term exposure to corticosterone is known to have deleterious effects on health. The researchers suggest that the high-anxiety mice may be more likely to become overly stressed in response to daily stressors, leading to chronically elevated levels of corticosterone. The next step will be for the researchers to determine whether treating chronic anxiety, such as with anti-anxiety medications, can enhance the benefits of cancer treatment.