Effects of Chronic Stress Can be Traced to Your Genes

New research shows that chronic stress changes gene activity in immune cells before they reach the bloodstream. With these changes, the cells are primed to fight an infection or trauma that doesn’t actually exist, leading to an overabundance of the inflammation that is linked to many health problems.

This is not just any stress, but repeated stress that triggers the sympathetic nervous system, commonly known as the fight-or-flight response, and stimulates the production of new blood cells. While this response is important for survival, prolonged activation over an extended period of time can have negative effects on health.

A study in animals showed that this type of chronic stress changes the activation, or expression, of genes in immune cells before they are released from the bone marrow. Genes that lead to inflammation are expressed at higher-than-normal levels, while the activation of genes that might suppress inflammation is diminished.

Ohio State University scientists made this discovery in a study of mice. Their colleagues from other institutions, testing blood samples from humans living in poor socioeconomic conditions, found that similarly primed immune cells were present in these chronically stressed people as well.

“The cells share many of the same characteristics in terms of their response to stress,” said John Sheridan, professor of oral biology in the College of Dentistry and associate director of Ohio State’s Institute for Behavioral Medicine Research (IBMR), and co-lead author of the study. “There is a stress-induced alteration in the bone marrow in both our mouse model and in chronically stressed humans that selects for a cell that’s going to be pro-inflammatory.

“So what this suggests is that if you’re working for a really bad boss over a long period of time, that experience may play out at the level of gene expression in your immune system.”

The findings suggest that drugs acting on the central nervous system to treat mood disorders might be supplemented with medications targeting other parts of the body to protect health in the context of chronic social stress.

Steven Cole, a professor of medicine and a member of the Cousins Center for Psychoneuroimmunology at UCLA, is a co-corresponding author of the study. The research is published in a recent issue of the journal Proceedings of the National Academy of Sciences.

The mind-body connection is well established, and research has confirmed that stress is associated with health problems. But the inner workings of that association - exactly how stress can harm health - are still under investigation.

Sheridan and colleagues have been studying the same mouse model for a decade to reveal how chronic stress - and specifically stress associated with social defeat - changes the brain and body in ways that affect behavior and health.

The mice are repeatedly subjected to stress that might resemble a person’s response to persistent life stressors. In this model, male mice living together are given time to establish a hierarchy, and then an aggressive male is added to the group for two hours at a time. This elicits a “fight or flight” response in the resident mice as they are repeatedly defeated by the intruder.