Molecular Effects of Social Stress

Rhesus macaques at the Yerkes National Primate Research Center were used in the study.Yerkes National Primate Research Center, Emory University.

Social rank has broad effects on gene regulation, particularly in the immune system, according to a new study in rhesus macaques. The findings help explain how social status gets under your skin.

Many species, including humans, have social hierarchies that affect mating and other behaviors that are important for survival. A growing body of evidence suggests that the stress of a low social ranking can also influence mental and physical health in a variety of ways. These include suppressed immune function and elevated risk for cardiovascular problems like hypertension, heart disease and stroke. Yet little is known on a molecular level about how social stress translates into physiological changes.

In the new study, researchers investigated whether social status affects gene regulation. The work, funded by several NIH components, was led by University of Chicago researchers Dr. Jenny Tung (now at Duke University) and Dr. Yoav Gilad. It was described in the April 9, 2012, advance online edition of the Proceedings of the National Academy of Sciences.

The researchers examined social groups of female rhesus macaques. In the wild, female macaques generally inherit their social rank from their mothers and stay in the social group they were born into. The scientists, however, constructed 10 groups with 5 macaques each. In this situation, the order of introduction determines rank, with later admission bringing lower status. The scientists took blood samples and used DNA microarray chips to analyze the blood cell expression levels of over 6,000 genes.

The team identified almost 1,000 genes whose expression levels varied with social rank. Over 500 were more highly expressed in high-ranking macaques; about 450 were more highly expressed in low-ranking animals. The largest functional group, with 112 genes, related to the immune system. The researchers found that, by looking at these expression levels, they could correctly predict social rank for 80% of the macaques they tested.

The social status of 7 macaques changed during the study, giving the scientists an opportunity to confirm that gene expression changes with social rank. They found that gene expression levels could correctly determine the social rank of 6 out of the 7 females.

The scientists also explored whether DNA methylation—an alteration that affects gene expression without changing the genetic sequence­—might mediate these effects. They found that the DNA methylation differences were modest but corresponded with expression. The finding provides at least a partial explanation for how the body might quickly change expression in response to social rank.

“There's a spooky side to this kind of research, in that an individual's social rank is partially determining health status,” Tung says. “But there's also a hopeful side. For the 7 females that changed ranks, their gene status changed with them. They're not stuck in place, and I think that says something more broadly about the capacity for change.”

This study provides insight into the links researchers have long observed between social stress and physiology. More work will be needed to fully understand the mechanisms by which social status affects gene expression and health outcomes.

—by Harrison Wein, Ph.D.