While inflammation has been known to be associated with depression and anxiety, an unanswered question has been whether inflammation predates and can actually contribute to the development of mental illnesses. The answer, based on new research published online on October 20th in the Proceedings of the National Academy of Sciences (PNAS), appears to be “yes” for patients susceptible to the effects of stress—and it may be possible to reverse the inflammatory effect in those individuals.  

The first author of the paper is 2012 NARSAD Young Investigator Grantee Georgia E. Hodes, Ph.D, and the research was led by Scott J. Russo, Ph.D., 2008 and 2006 NARSAD Young Investigator Grantee, both of the Icahn School of Medicine at Mount Sinai. Foundation Scientific Council Member Bruce S. McEwen, Ph.D., longstanding expert on the link between stress hormones and depression, edited the paper. Their work shows that pre-existing differences in the peripheral immune systems of individuals can promote—and predict—individual resilience or susceptibility to the effects of stress that can lead to stress-related disorders. They also show that it may be possible to manipulate the system therapeutically to reverse the negative behavioral effects in those susceptible to stress.

Depression and anxiety disorders are associated with an increase in levels of cytokines, proteins released by the body’s peripheral, or innate, immune system in response to stress. Working with mice, the researchers found that replacing the peripheral immune system of an unstressed mouse with the system of a stressed mouse made the previously unstressed mouse highly susceptible to the effects of stress.

Of the cytokines regulated by stress, interleukin 6 (IL6) was the most highly increased, but only in mice that proved most susceptible to developing depression-like symptoms. The researchers then confirmed a similar elevation of IL6 in two separate groups of human patients with treatment-resistant depression. In their mouse model, they were able to engineer progenitor cells that could shift sensitivity from a susceptible to a resilient state.

“These studies demonstrate that the emotional response to stress can be generated or blocked in the periphery,” the authors conclude, “and offer a potential new form of treatment for stress disorders.”

Other NARSAD Grantees involved in the work include James W. Murrough, M.D., 2009 NARSAD Young Investigator Grantee, at the Icahn School and 2005 NARSAD Independent Investigator Grantee Sabine Bahn, M.D., Ph.D., MRCPysch, of the University of Cambridge.

Read the abstract of this research paper.