Social rejection may leave more than emotional scars — too much of it might lead to diseases, new brain research shows.

When experiencing the cold shoulder, participants in a study showed activity in two brain regions, which led to an increase in inflammation in the body. Inflammation is an immune response and can be beneficial when your body is fighting off infection, but chronically high levels of inflammation are known to play a role in certain disorders, including asthma, cardiovascular disease and even depression.

Some people may be more prone to these boosts in inflammation than others. Study participants whose brains indicated they were particularly sensitive to social rejection had greater increases in inflammation in response to social stress.

"This really starts to understand mind-body connections in a way that we haven't been able to do before," said study researcher George Slavich of UCLA.

"Let's just say for argument's sake that if you exhibit that neural sensitivity to social rejection in daily life, you could be having these increases in inflammation throughout the course of a day or week," Slavich said. "Increases in inflammatory activity are a very adaptive response when you have them once in a while, but to have lots of these activations over the course of a day or a week could potentially lead to chronic levels of inflammation which can be damaging to other cells and to organs."

Stressful Experiments

Researchers knew that when test subjects are exposed to social stress, their bodies respond with increases in inflammation. But not everyone responds in exactly the same way, Slavich said. Some people find such activities more distressing than others and show greater upticks in their inflammatory responses.

To examine the neural basis for such biological differences, Slavich and his colleagues first made 124 volunteers very socially uncomfortable.

Participants were asked to give a five-minute impromptu speech standing alone in front of a panel of raters. The raters wore white coats and acted frigidly, showing no response to the speech, as if they thought it lacked quality.

Next the participants were again surprised by being asked to perform some challenging mental arithmetic. They had to count backward from 2,935 by 7's and by 13's. The experimenter kept prompting the subjects to pick up the pace, and if they made a mistake, they had to start over.

The researchers collected saliva from the participants before and after the stress-causing situation and examined it for two proteins that are key markers of inflammation.

Thirty-one of the participants also had their brains scanned by functional magnetic resonance imaging (fMRI) while they took part in another social-rejection experiment. Each subject was told he or she would be playing a ball-tossing computer game with two other participants. In fact, the two other participants were not volunteers, but computer-generated "players."

In the fMRI scanner, subjects saw a computer screen with a virtual hand to represent themselves and two cartoon characters representing the other two "participants." In the first round of the game, the subject received the ball and could toss it back and forth with the other players. In the second round, the subject never received the ball, and so experienced social rejection.

The researchers examined activity in two brain regions, the dorsal anterior cingulated cortex and the anterior insula. They compared the activity in these regions when the subject was included in the game to the activity when the subject was excluded. The greater the difference, the more sensitive the subject was to social rejection.

Link to depression?

Subjects who were the most sensitive to social rejection in the fMRI scanner also had the greatest increases in their inflammatory markers during the social stress experiment.

The findings may explain why some people are particularly prone to inflammatory conditions. It may even explain how social rejection can cause depression, a condition often characterized by high levels of inflammation, Slavich said.

"We talk about stress and depression so often in our daily lives that we just assume that stress can directly cause depression," he said. "But it's an extremely complex question." Stress occurs outside the body, yet can lead to many changes inside, he said.

"Depression is not just about feeling sad, it's also about changes in sleep and changes in eating and feeling fatigued for some individuals, so it's a very systemic problem," Slavich said.

The results are being published this week in the journal Proceedings of the National Academy of Sciences, suggest one way in which social rejection gets processed by the brain in such a way that the result is a boost in inflammation, Slavich said.

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