Social rank: Stressed out by NMR

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  • Published: Aug 1, 2017
  • Author: David Bradley
  • Channels: NMR Knowledge Base
thumbnail image: Social rank: Stressed out by NMR

Hierarchical stress

Scientists have shown how rank in social hierarchies is a major determining factor for vulnerability to chronic stress, NMR clues in metabolism.

Social ranking is a major determining factor for vulnerability to chronic stress, according to a new study that uses nuclear magnetic resonance (NMR) spectroscopy to look at energy metabolism in the brain as a predictive biomarker.

Stress is an important risk factor for a wide range of physical and mental health problems. However, there is no one-to-one correlation with stress levels and any detrimental effects. Each of us responds to stress differently, whether it is chronic stress or an acute episode. Indeed, sustained adversity leads to depression in some people while others adapt and remain resilient. It is important to identify the biological factors that correlate with vulnerability or resilience in order to provide better healthcare for those with stress-induced depression.

Scientists at EPFL (École polytechnique fédérale de Lausanne, in Switzerland) have now demonstrated that social hierarchy, or organization, can affect how people respond to differential vulnerability to chronic stress. It seems that brain energy metabolism is a predictive biomarker for social status and susceptibility to stress-induced depression, the team reports in the journal Current Biology.


EPFL's Carmen Sandi and her colleagues have focused on stress for a long time. In earlier work they have found that laboratory mice repeatedly exposed to negative, defeat, experiences, can show symptoms that we would associate with depression in people, including the avoidance of social contact. Conversely, other mice exposed to the same stresses behave as if they are unstressed, and retain their normal social interests. Much of this earlier work, while informative, was used to identify vulnerabilities in the lab mice based on symptoms developed after they were exposed to stress rather than looking for signs of predisposition to problems prior to stress.

It was already known that the differential vulnerability to depression following stress is present in laboratory mice known as C57BL/6J which are all identical genetically speaking. Moreover, the environment, the housing and living conditions, in which the mice find themselves, are also identical. These two experimental facts preclude the influence of genetic factors and issues related to early life trauma.

The team points out that mice are usually housed in groups, four to a cage, and this they suggest allows social hierarchical order to be established within each cage. This factor thus becomes one of the only differentiators between the individual mice given their genetics and environment are otherwise the same. The team gave the mice from the same home cage competitive challenges, that they hoped would allow the research to reveal dominant and subordinate animals in each group. When they then applied chronic stress exposure to the mice, they could study how the dominant and subordinate animals differed in their response to the stress. It seems that the dominant mice displayed a prominent susceptibility to stress by showing strong social avoidance whereas the subordinate mice were unaffected by the detrimental effects of stress, they apparently shrugged off the stress and behaved as if they had not been stressed at all.

Metabolic indications

With these insights in hand, the team then worked with EPFL's Rolf Gruetter and his team to carry out proton nuclear magnetic resonance spectroscopy to measure metabolite levels in the mouse brain, specifically in the nucleus accumbens, which is involved in motivation and reward, and the medial prefrontal cortex, which is involved in planning.

The NMR showed that the metabolic profile of the nucleus accumbens relates to social status and vulnerability to stress. More specifically, non-stressed, subordinate individuals showed lower levels of metabolites related to energy metabolism (glutamate, phosphocreatine, total creatine, N-acetylaspartate, and taurine) in the nucleus accumbens than the dominant mice. Following exposure to chronic stress, the concentrations of these metabolites increased in the subordinate, but not in the dominant mice.

This is the first non-invasive study to identify risk factors and biomarkers associated with social status and what one might assume is stress-induced depression. Of course, how this translates to people remains to be seen. At the experimental level, the findings might allow new progress to be made in investigating of mechanisms related to vulnerability and resilience to stress. It could be that for the dominant individuals their expectations are higher because they are at the top of the hierarchy and they thus succumb to the problems of stress more than sub-ordinate individuals for whom the bar is set lower.

“Our findings reinforce the view that losing status is more pertinent to depression than social subordination,” explains Sandi. “It will be important to study whether social status can also predict depression or anxiety when individuals are chronically exposed to stressors of a non-social nature," she suggests. Sandi's group is now hoping to investigate the value of interventions that target energy metabolism in the brain, in order to help vulnerable individuals to cope with stress.

Related Links

Curr Biol 2017, online: "Hierarchical status predicts behavioral vulnerability and nucleus accumbens metabolic profile following chronic social defeat stress"

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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