Psychological stress may be deadly. Feeling lonely, depressed or socially rejected sets off alarm bells in the brain similar to those from a physical injury hurt and triggers activity in genes linked to inflammation. Inflammation is related to a number of serious diseases including cancer, heart disease and depression.

"It is clear that our emotional state is intimately linked to our physical health," said Steven Cole, an associate professor of medicine at the University of California, Los Angeles, who was not involved in the study. "However, it is less clear how all the components work together to influence our physical well-being."

Now researchers at UCLA have uncovered a possible pathway linking social stress, the brain and inflammation.

The new study, published online Tuesday in Proceedings of the National Academy of Sciences, brings together a string of recent papers that have pinpointed regions of the brain that process stress and proteins that become hyperactive in response to chronic loneliness or depression.

To see if emotional stress might trigger inflammation in the body, George Salvich and his team recruited 124 healthy people, ages 18 to 36, to give a five-minute impromptu speech in front of a panel of stone-faced raters wearing white lab coats. The participants were also judged on their ability to count backward from 2,935 by sevens and 13s, and had to start over if they messed up.

Salvich's team found that participants were sensitive to the judgmental, high-pressure conditions, experiencing a spike in two proteins associated with inflammation -- interleukin-6 6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). The IL-6 protein, in particular, may be a clue to the overall health impacts of stress. A 2008 study published in the Journal of the American College of Cardiology found that among the several key markers of inflammation, including C-reactive protein, IL-6 was the best predictor of heart failure.

Several weeks later, the researchers brought back 31 of the original participants to play a video game called Cyberball while lying in a magnetic resonance imaging machine. During the Cyberball games, one participant tossed a virtual ball back and forth with two other players, but was ultimately excluded from the match. The researchers found that feeling excluded increased activity in the parts of the brain that process stress -- specifically the dorsal anterior cingulate cortex (dACC) and the anterior insula.

In both sets of tasks, some participants were more sensitive to feeling judged or being excluded than others. Those who showed the most activity in those two brain regions during the video game also exhibited the largest spikes in inflammatory activity, specifically in TNF-alpha, during the mental tasks.

"This link between heightened brain activity and inflammation wouldn't likely happen by chance since the experiments were done weeks apart," said Cole, who was not involved in the study.

The results, however, do not tell us whether the brain's response to social stress drives the inflammatory one. "It's possible that the inflammation influences brain function or that something else is causing both processes," said Cole. "We're not quite at the point of identifying a stress pathway."

Slavich said that it seems more likely that stress triggers activity in the brain, which then triggers inflammation in the body. "The same neural circuitry that processes social rejection also tells the body it's in physical pain," said Slavich. "We know that physical pain, or the possibility of physical pain, triggers inflammation in the body, which helps us manage and repair the injury." Thus, perhaps the same process occurs in people who feel social pain. However, the next step is to understand exactly how the dACC and anterior insula might cause this inflammation, Slavich noted.

"Another interesting question the study raises is why some people were more sensitive to the social rejection while others were more resilient," said Cole. "People's different stress thresholds could stem from genetics, environment, or some combination of the two, but understanding the reason for this sensitivity could help us treat chronic stress."