Anxiety could be linked to the progression of cancer, according to a new study led by researchers at the Stanford School of Medicine in which high-anxiety mice showed accelerated cancer progression compared to their more assured peers.

“Even though we hypothesized this before conducting our experiments, it was still surprising to observe that a psychological trait – before any experimental manipulation – was associated with increased tumor progression weeks and months later,” said Firdaus Dhabhar, professor of psychiatry and behavioral sciences and the study’s first author.

Employing controlled doses of ultraviolet radiation to replicate the effects of repeated sun exposure – and thus prompt the onset of skin cancer – the study found that high-anxiety mice developed more numerous and more invasive tumors after several months.

“The important advantage [of this research design] is that the model shows a time course and pathology of tumors that is very similar to that seen in people,” Dhabhar said.

The mice’s tendencies toward high- or low-anxiety characteristics were measured using ethological tests in which the mice were presented with simultaneous, conflicting motivations to explore and to assure safety.

For example, in one test set, mice were placed in an arena divided between light and dark sectors.  High-anxiety mice would more often seek safety and concealment by spending more time in the dark.

Precancerous lesions appeared in all mice within weeks after the light exposure, and tumors developed within months. Only high-anxiety mice developed invasive cancer.

“[High-anxiety individuals] are likelier to mount larger and longer biological stress responses to a given stressor,” Dhabhar said, noting that the results were similar to previous studies in which external chronic stressors were introduced.

“Moreover, a high-anxiety individual may mount a response in some situations where a low-anxiety individual might not respond at all,” Dhabhar added.

The accelerated tumor proliferation and invasiveness in the high-anxiety mice can be linked to a variety of biological markers, such as increased levels of the stress hormone corticosterone, a lack of immune cells involved in protecting against skin cancer and even the production of cells that suppress protective immunity.

While the harmful effect of chronic stress on immune function is well-documented, the study is the first to connect cancer progression to the psychological tendency for anxiety. In the future, Dhabhar and the team intend to expand their research to examine how this relationship translates to humans.

“I believe that the critical connection between mind and body needs to be further investigated using the tools, techniques and language of modern science,” Dhabhar said. “Doing this will make the mind-body connection better understood and more widely accepted and, [more] importantly, make it possible for doctors and patients to work with and harness this connection in ways that would help people.”

With an accurate model in place, Dhabhar said that he anticipates the study’s findings and implications to be utilized in new medical approaches to cancer therapy.

“The bottom line is that following up these studies and their applicability to humans will require a significant amount of systematic effort,” he said. “However, that is the nature of science, and it is very well worth doing if there is a reasonable chance that it will help those who are ill.”

Dhabhar cited drugs and cognitive-behavioral approaches as potentially being capable of ameliorating the effects of anxiety on cancer progression, though he stressed the need for careful research and pharmaceutical development to safeguard against counterproductive interactions between cancer drugs and antidepressants.

“It’s bad enough that cancer diagnosis and treatment generate stress and anxiety, but this study shows that anxiety and stress can accelerate cancer progression, thus perpetuating a vicious cycle,” Dhabhar said. “The goal is to try to ameliorate or eliminate the effects of anxiety and chronic stress especially at the time of cancer diagnosis and during treatment.”