Researchers at the University of Illinois report that IDO, an enzyme found throughout the body and long suspected of playing a role in depression, is in fact essential to the onset of depressive symptoms sparked by chronic inflammation.
Their study, just published online in the Journal of Immunology, is the first to identify IDO (indoleamine 2,3 dioxygenase) as a molecular switch that induces depressive symptoms in some cases of chronic inflammation.
Doctors have known for decades that patients with chronic inflammation, such as that linked to coronary heart disease or rheumatoid arthritis, are more likely than others to become depressed. Some pro-inflammatory drugs, such as interferon-alpha, which is used to treat Hepatitis C and a cancer known as malignant melanoma, also induce symptoms of depression in a significant number of patients.
In the new study, mice were exposed to Bacille CalmetteGurin (BCG), a vaccine used in many parts of the world to prevent tuberculosis. BCG produces low-grade, chronic inflammation in mice, which can be detected by measuring levels of certain immune system proteins, called inflammatory cytokines, in the blood and brain.
Mice exposed to BCG display the normal symptoms of illness (lack of appetite, reduced activity), but after these symptoms fade the mice continue to exhibit depressive-like behaviors that can be reversed with antidepressants, said animal sciences and pathology professors Keith Kelley and Robert Dantzer, who led the study.
Even after they recover from their sickness, the BCG-infected mice are much more passive than non-infected mice when in an inescapable situation. When placed in a bucket of water for a few minutes, for example, they struggle less to escape and spend more time floating passively, the researchers report.
"The mice that we're calling depressed give up more quickly. While physically able, the mice quit trying to escape," said animal s
|Contact: Diana Yates|
University of Illinois at Urbana-Champaign