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The biology behind why some people manage stress worse than others

September 8, 2014

NeuronsSome people stand up to stress while others struggle with it. But until recently, scientists did not greatly understand this so-called “stress gap.”

New research has pinpointed the molecular origins of stress in mice, and the results could contribute to better understanding the development of depression and other disorders induced by stress.¹ Medical assisting professionals may see patients suffering from depression on a regular basis, and unveiling the underlying molecular mechanisms for the onset of the disorder could present new routes for treatment options.

Relationship between stress and depression

It’s widely known that stress has become an epidemic in the U.S. About one-third of Americans report living with extreme stress, according to the American Psychological Association.² Whether chronic or acute, stress can lead to depression in susceptible individuals. It does this by sending the body’s stress-response mechanism into a state of overactivity. Sustained stress increases hormones such as cortisol, which is called the “stress hormone,” and reduces serotonin, dopamine and other neurotransmitters in the brain. Consistently low levels of dopamine are associated with depression.

Markers in stress-related disorders

For the recent study published in Molecular Psychiatry, scientists at Rockefeller University honed in on potential new molecular markers in mice. In the experiments, the animals were exposed to stressful events daily such as confinement in tight spaces, unpredictable bouts of cage tilting, altered dark-lights cycles and other situations to trigger stress hormones.

They found while about 60 percent coped well with the anxiety, 40 percent showed high levels of behavior that included a loss of interest in sugar water and a preference in a dark compartment over a brightly lit one. The discrepancy between the vulnerable mice and the resilient ones was so underlying that it emerged even before the mice were subjected to stress.

The researchers discovered in the highly stress-susceptible mice, there was less of an important molecule called Metabotropic glutamate receptor 2 (mGlu2) in the hippocampus region of the brain, where much of one’s internal stress-related activity is centered. The mGlu2 decrease, the scientists noted, was brought on by an epigenetic change, which alters the expression of genes, in this case the gene that codes for mGlu2.

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

Previous research has linked mGlu2 in the cognitive impairment reported by patients suffering from major depression.⁴ Nasca and her fellow researchers had showed that a potential depression treatment know as acetyl carnitine rapidly alleviated depression-like symptoms in rats and mice by reversing epigenetic changes to mGlu2, increasing the molecule’s levels.

Addressing the root of the problem

People in medical assistant programs understand that the best way to treat a patient is to resolve the underlying problem rather than palliating symptoms. Better yet, doctors could confront the problem before symptoms even arise, but unfortunately this is not yet the case for depression.

“Currently, depression is diagnosed only by its symptoms,” Nasca explained. “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.”

By further grasping the underlying mechanisms in depression, those entering the medical community from medical assisting college can head down new avenues for diagnosis and treatment of the often debilitating disorder.

¹Nasca, C., Bigio, B., Nicoletti, F., & McEwen, B. (2014, September 2). Research hints at why stress is more devastating for some. Retrieved September 4, 2014, from

²Stress a Major Health Problem in The U.S., Warns APA. (2007, October 24). Retrieved September 4, 2014, from

³Feature, K. (2011, April 12). The Stress-Depression Connection | Can Stress Cause Depression? Retrieved September 4, 2014, from

⁴Goeldner, C., Ballard, T., Knoflach, F., Wichmann, J., Gatti, S., & Umbricht, D. (2008, August 1). Cognitive impairment in major depression and the mGlu2 receptor as a therapeutic target. Retrieved September 4, 2014, from http://w

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