When it comes to the way stress affects individuals, with some able to receive stressful circumstances in stride when others end up overwhelmed by even the smallest hints of pressure, its all molecular, apparently.

New research out of Rockefeller University in New York has identified the molecular mechanisms in lab mice that prompt how the critters respond to stressful situations.

"Like people, each animal has unique experiences as it goes through its life. And we suspect that these life experiences can alter the expression of genes, and as a result, affect an animal's susceptibility to stress," senior research author Bruce McEwen, an Alfred E. Mirsky Professor and head of the university's Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, said in a news release. "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 and his colleagues examined the process by which stress produces in the behaviors of mice approximating human reactions to anxiety and depression, stressing the rodents by exposing them to daily, unpredictable bouts of cage tilting, altered dark-light cycles, confinement in tight spaces and other conditions mice dislike.

The initial goal was to reproduce the sort of stressful experiences thought to be a main cause of depression in humans.

Afterward, in tests to see if the mice displayed the rodent equivalent of anxiety and depression symptoms, the scientists discovered about 40 percent showed high levels of behaviors that included a preference for a dark compartment over a brightly lit one, as well as a loss of interest in sugar water.

The other 60 percent of the mice appeared to recover well from the series of stressors.

The distinction between the susceptible and resilient mice was so fundamental that the differences were apparent in their respective behaviors, even before the stress test was administered.

It was discovered the highly stress-susceptible mice had less of an important molecule known as mGlu2 in the regions of their brains known as the hippocampus, where much of one's internal stress-related activity is centered.

That decrease in mGlu2, the research team learned, was the result of an epigenetic change, a shift in the way an individual's genes -- in this case the gene that codes for mGlu2 -- determine an individual's characteristics.

"If you think of the genetic code as words in a book, the book must be opened in order for you to read it. These epigenetic changes, which affect histone proteins associated with DNA, effectively close the book, so the code for mGlu2 cannot be read," said the study's first author Carla Nasca, a postdoc in the lab and a fellow of the American Foundation for Suicide Prevention.

Nasca and her fellow researchers previously found the link between levels of mGlu2 and depression when they showed that a potential depression treatment known as acetyl carnitine rapidly alleviated depression-like symptoms in rats and mice by reversing epigenetic changes to mGlu2 and causing its levels to increase.

"Currently, depression is diagnosed only by its symptoms," Nasca said. "But these results put us on track to discover molecular signatures in humans that may have the potential to serve as markers for certain types of depression. Our work could also lead to a new generation of rapidly acting antidepressants, such as the candidate acetyl carnitine, which would be particularly important to reduce the risk of suicide."

Said McEwen: "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 ... studies like this one are increasingly focusing on the regulation of glutamate as an underlying mechanism in depression and, we hope, opening promising new avenues for the diagnosis and treatment of this devastating disorder."