The Inflammasome: Pathways Linking Psychological Stress, Depression, and Systemic Illnesses

Stress is a common occurrence in everyday life and repeated or traumatic stress can be a precipitating factor for illnesses of the central nervous system, as well as peripheral organ systems. For example, severe or long-term psychological stress can not only induce depression, a leading illness worldwide, but can also cause psychosomatic diseases such as asthma and rheumatoid arthritis. Related key questions include how psychological stress influences both brain and peripheral systems, and what detection mechanisms underlie these effects? A clue is provided by the discovery of the pathways underlying the responses to host "danger" substances that cause systemic diseases, but can also contribute to depression. The inflammasome is a protein complex that can detect diverse danger signals and produce the accompanying immune-inflammatory reactions. Interestingly, the inflammasome can detect not only pathogen-associated molecules, but also cell damage-associated molecules such as ATP. Here, we propose a new inflammasome hypothesis of depression and related comorbid systemic illnesses. According to this hypothesis, the inflammasome is a central mediator by which psychological and physical stressors can contribute to the development of depression, and as well as a bridge to systemic diseases. This hypothesis includes an explanation for how psychological stress can influence systemic diseases, and conversely how systemic diseases can lead to psychiatric illnesses. The evidence suggests that the inflammasome may be a new target for the development of treatments for depression, as well as psychosomatic and somato-psycho diseases.