Why stress can be more distressing for some people revealed

A new study has found why some people take stress in stride while others face a more devastating effect.

Researchers at Rockefeller University have identified the molecular mechanisms of this so-called stress gap in mice with very similar genetic backgrounds, a finding that could lead researchers to better understand the development of psychiatric disorders such as anxiety and depression.

In experiments, researchers stressed mice by exposing them to daily, unpredictable bouts of cage tilting, altered dark-light cycles, confinement in tight spaces and other conditions mice dislike with the goal of reproducing the sort of stressful experiences thought to be a primary cause of depression in humans.

Afterward, in tests to see if the mice displayed the rodent equivalent of anxiety and depression symptoms, they found about 40 percent showed high levels of behaviors that included a preference for a dark compartment over a brightly lit one, or a loss of interest in sugar water. The remaining 60 percent coped well with the stress. This distinction between the susceptible mice and the resilient ones was so fundamental that it emerged even before the mice were subjected to stress, with some unstressed mice showing an anxiety-like preference for a dark compartment over a lighted one.

The researchers found that the highly stress-susceptible mice had less of an important molecule known as mGlu2 in a stress-involved region of the brain known as the hippocampus. The mGlu2 decrease, they determined, resulted from an epigenetic change, which affects the expression of genes, in this case the gene that codes for mGlu2.

A reduction in mGlu2 mattered as the molecule regulated the neurotransmitter glutamate. While glutamate played a crucial role relaying messages between neurons as part of many important processes, too much could lead to harmful structural changes in the brain.

Senior author Bruce McEwen said that since the brain constantly changes, when stressful experiences lead to anxiety and depressive disorders, it becomes locked in a state it cannot spontaneously escape. Studies like this one increasingly focus on the regulation of glutamate as an underlying mechanism in depression and they hoped to open promising new avenues for the diagnosis and treatment of this devastating disorder.

The study is published in Molecular Psychiatry.