Scientists at the Harvard-affiliated McLean Hospital recently discovered that long-term exposure to stress hormones may be the cause of some symptoms of depression.

Researchers wanted to determine the exact nature of the long-recognized link between high cortisol levels and depression. Cortisol, a hormone released in response to stress, increases blood pressure and blood sugar, preparing the body to deal with a stressor.

Paul A. Ardayfio, a graduate student at the Harvard Medical School who ran these experiments as part of his dissertation, explained that “we’ve known for over a century that chronically high levels of cortisol were linked to depression, so we decided to test whether or not cortisol directly caused some symptoms of depression.”

The study found that chronic exposure to cortisol may cause some symptoms of depression, but did not find evidence that it causes depression itself.

Ardayfio cautioned against understanding his results as demonstrating a simple cause and effect relationship.

“Depression is a very heterogeneous disorder and it has many different causes,” he said. “This may be one part of the puzzle for one particular kind of depression.”

Ardayfio and his advisor, Associate Professor of Psychiatry Kwang-Soo Kim, tested three groups of mice on a standard anxiety-level test. The mice were placed in a darkened chamber, allowed to acclimatize themselves, and were then allowed to explore another brightly lit chamber.

Ardayfio and Kim found that, while normal mice readily explored the new area, mice which had received long-term doses of the rodent equivalent of cortisol via drinking water were reluctant to explore and exhibited symptoms that the researchers characterized as anxiety.

Anxiety in mice placed in this experimental setup generally predicts how humans will react to stress.

In another experiment, Ardayfio and Kim showed that chronically dosed mice reacted less strongly to sudden stress, a sign that they were burnt out.

After Ardayfio defends his dissertation next month, he hopes to study the cellular and molecular pathways associated with cortisol. He said that such research could lead to novel treatments for depression.

“By examining the real causes of depression, we could make progress to an effective treatment.”