Does high anxiety increase the severity of disease?

The thought has crossed many minds: does a nervous demeanor actually increase the likelihood that one will get sick, or even affect the severity of an illness? Evidence of a correlation between physiological stress responses and the risk of cancer does exist, however, the findings haven’t always been consistent (Antoni et al., 2006). To provide more answers, Dhabhar et al. published a study last month in PLoS One, examining the development of skin cancer in normal mice with either a high or low anxiety phenotype.

One of the most interesting features of this study is that mouse anxiety phenotypes were determined not by genetic modulation, but rather by natural variations in the animal’s demeanor. Using the Elevated Plus Maze, Light-Dark Arena, and Open Field Arena behavioral assays, the authors delineated which mice were more or less prone to experience heightened levels of anxiety, and separated them into groups for further study, a method closely resembling the temperamental variation in human populations. Mice were of a normal, out-bred population and were exposed to UV light on a regular basis over the course of 10 weeks, again more closely matching what is seen as the cause of some human cancers. Because chronic stress has been shown to increase susceptibility to squamous cell carcinoma by suppressing protective immunity (Antoni et al., 2006), the authors then examined tumor emergence and progression, as well as measured quantities of protective chemokines and cell types in the blood, tumors, and lymph nodes.

They found that anxious mice showed an increased tumor count in three separate stages of cancer: a pre-cancerous papilloma stage, transition to squamous cell carcinoma, and carcinoma progression. However, anxious mice did not develop these stages any earlier than non-anxious mice. In addition to advanced tumor progression, UV-exposed skin showed a significant decrease in the mRNA levels of protective chemokines and cytokines. Tumors themselves showed an increase in the mRNA of harmful cytokines relative to helpful cytokines. The number of protective tumor-infiltrating T cells also was decreased in tumors, as examined by immunohistology. All parameters were examined up to 31 weeks after the study began.

All told, while high-anxiety mice did not develop tumors any sooner than low-anxiety mice, anxious mice did develop more tumors, and had reduced expression of protective cell mediators in skin and tumor tissue. High-anxiety mice also had higher levels of circulating corticosterone, suggesting a potential connection between the endocrine system and tumor progression.

The authors of this study suggest that behavioral and pharmacological anxiolytics could be given to patients (especially those with high-anxiety personalities) following diagnosis and during treatment. New findings such as these indicate that such measures might improve patients’ chances of survival.

What do you think?

Are you convinced that physiological stress effects (such as corticosterone levels) can increase cancer potency?

How does stress effect the development or progression of other diseases?

Further Reading:

Antoni MH, Lutgendorf SK, Cole SW, Dhabhar FS, Sephton SE, McDonald PG, Stefanek M, Sood AK. (2006). The influence of bio-behavioural factors on tumour biology: pathways and mechanisms. Nat Rev Cancer. Mar;6(3):240-8.

Dhabhar FS, Saul AN, Holmes TH, Daugherty C, Neri E, Tillie JM, Kusewitt D, Oberyszyn TM. (2012). High-anxious individuals show increased chronic stress burden, decreased protective immunity, and increased cancer progression in a mouse model of squamous cell carcinoma. PLoS One. 7(4):e33069. Epub 2012 Apr 25.