Stress hormone linked to behaviour
Baltimore, September 18, 2010
Long-term exposure to a common stress hormone may leave a lasting mark on the genome and influence how genes that control mood and behavior are expressed, a study said.
The study led by Johns Hopkins researchers said that the finding could eventually lead to new ways to explain and treat depression, bipolar disorder, and other mental illnesses.
Scientists and physicians have long been interested in the cause of depression, a sometimes debilitating disorder that affects about 16 per cent of people at least once over the course of a lifetime.
While studies have shown that many other mental illnesses are strongly heritable, studies have shown that the risk of depression is only about 40 per cent genetic. Consequently, environmental factors are thought to play a major role in causing this disease.
Previous research has shown that stressful life events can increase the risk of depression. But how these life events play into the biology of this disease is unknown, the study said.
James Potash, MD, MPH, an associate professor at the Johns Hopkins University School of Medicine, and colleagues suspected that epigenetic factors might be at work in the disease.
Epigenetic, or “above the genome,” factors are so named because they affect how genes are expressed without changing the genetic sequence. One of the most prevalent epigenetic changes, or “marks,” are methyl chemical groups that clip onto DNA, often shutting off the gene that they attach to.
To see if stress might influence epigenetic marks on genes involved in depression, Potash and his Johns Hopkins colleagues gave some mice corticosterone in their drinking water for four weeks.
Corticosterone is the mouse version of cortisol, a hormone produced by the human body during stressful situations. Other mice drank plain water without this hormone.
At the end of the four-week period, the mice who received corticosterone displayed anxious characteristics in behavioral tests. Gene expression tests on these animals showed a marked increase in protein produced by a gene called Fkbp5. This gene’s human form has been linked to mood disorders, including depression and bipolar disease.
“This gets at the mechanism through which we think epigenetics is important,” said Potash, who directs Johns Hopkins’ Mood Disorders Research Programs.
He explained that epigenetic marks that are added through life experience may prepare an animal for future events.
“If you think of the stress system as preparing you for fight or flight, you might imagine that these epigenetic changes might prepare you to fight harder or flee faster the next time you encounter something stressful,” Potash said.
These behaviors, which were probably advantageous earlier in evolution, aren’t as useful today with modern stressors that we can’t fight or flee, such as work deadlines, Potash added. Consequently, chronic stress might instead lead to depression or other mood disorders triggered by epigenetic changes.
Potash noted that, eventually, doctors may be able to look for these epigenetic changes in DNA isolated from a patient’s blood to predict or diagnose psychiatric illnesses.
Ultimately, researchers may someday be able to target these epigenetic marks with drugs to treat depression and other diseases, he added. – TradeArabia News Service
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