A new study conducted by Rockefeller University is providing some much needed insight into what researchers are calling the “stress gap"—the difference in stress tolerance between people of similar genetics. The research, published in Molecular Psychiatry, closely observed molecular mechanisms in mice, in order to better understand why some people are much more inclined to develop anxiety disorders than others who have experienced the same amount of stress.

Studying Stress Susceptibility

Researchers experimented on mice, exposing them to regular cycles of stress, such as cage-tilting, confinement, and altering light and dark environments. This was done in order to mirror stressful experiences that cause depression in humans. After assessing the rodents, scientists found that 40% exhibited behaviors characteristic of depression and anxiety disorders; they showed a loss of interest in sugar water and were more inclined to stay in dark compartments of their cage. The other 60% were found to cope well with stress.

Looking into their genetics, researchers found a significant difference between the mice that were able to deal with stress and the others that showed signs of depression and anxiety. The group that exhibited a high susceptibility to stress was discovered to have less of a molecule known as mGlu2 in the hippocampus, a region of the brain that is significantly stress-involved.

Why mGlu2 Matters

The protein mGlu2 regulates the neurotransmitter glutamate, which plays a crucial role in delivering messages between neurons of vital brain processes. "The brain is constantly changing. When stressful experiences lead to anxiety and depressive disorders the brain becomes locked in a state it cannot spontaneously escape," says senior author Bruce McEwen, professor and head of the Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology.

This study takes significant strides towards better understanding the development of anxiety and depression in individuals. By looking into the molecular structure of those who are more susceptible to stress, scientists can provide a clearer roadmap to treatment. “We have taken an important step toward explaining the molecular origins of this stress gap by showing that inbred mice react differently to stress, with some developing behaviors that resemble anxiety and depression, and others remaining resilient," McEwen adds.

Date of original publication:
Updated on: November 10, 2015


C Nasca, B Bigio, D Zelli, F Nicoletti, B S McEwen. Mind the gap: glucocorticoids modulate hippocampal glutamate tone underlying individual differences in stress susceptibility. Molecular Psychiatry, 2014; DOI: 10.1038/mp.2014.96