Some people are more prone to post-traumatic stress disorder
They found a key pathway in mice differs in those who cope well with stress, and those who do not.
The findings, published in Cell, could lead to new treatments for conditions such as post-traumatic stress disorder.
Experts said evidence increasingly showed responses to stress were linked to chemical mechanisms in the brain.
People differ widely in their responses to stressful situations - some people seem highly resilient to stress while others struggle to cope.
For example around a third of people may suffer post-traumatic stress disorder (PTSD) after an exceptionally traumatic event, such as a terrorist attack or a natural disaster.
The researchers, from the University of Texas Southwestern Medical Centre, looked at differences in mice facing a stressful situation in the form of a larger more aggressive mouse.
Some of the mice coped with the stress well and others became timid and withdrew from social interaction.
In the mice who did not cope well with stress, nerve cells fired signals at a faster rate in two areas of the brain associated with pleasure and reward, releasing a substance called BDNF, which has previously been linked to poor coping.
The resilient mice had no increase in BDNF, probably because the neurons were firing less rapidly.
Blocking BDNF in the timid mice caused them to become more resistant to stress.
In mice who coped better with stress, there were also greater regulation of genes in the key brain regions, suggesting resilience to such conditions is an active process rather than a lack of a response.
Analysis of brain samples from depressed and non-depressed humans, showed that depressed people have a 40% increased level of BDNF.
Preventing BDNF release in certain brain regions may be a way to increase coping ability to stress or depression, the researchers concluded.
"Chronic stress, depression, post-traumatic stress disorder and similar disorders might be treated by promoting the mechanisms that underlie resilience," Dr Eric Nestler, professor of psychiatry and study leader
However, he added that simply blocking BDNF might also affect other systems, so researchers would have to find a way to target the specific pathway involved in stress.
Dr Jonathan Bisson, senior lecturer in psychiatry at the University of Cardiff said one of the theories of why some people developed PTSD and others did not was that certain areas of the brain failed to dampen down the fearful response to a traumatic situation.
"If we can identify parts of the brain acting differently and look at the chemical changes in theory we can develop treatments."
Dr Martin Deahl, consultant psychiatrist in Shropshire said there was no doubt that chemicals in the brain were terribly important.
But he added: "It doesn't mean you're born with it, life experiences affects the make up of chemicals in the brain and why some people are vulnerable is not known exactly."