Experts in the United States say the results of a study with mice suggests that stress in itself may cause anxiety and depression.
The neuroscientists from Harvard Medical School and Mclean Hospital have shown that long-term exposure to stress hormones such as cortisol and a corticotropin-releasing hormone in mice results in the anxiety that often comes with depression.
Such hormones can help the response to an immediate threat.
They believe their findings support circumstantial evidence linking stress and depression, and may be the cause of some mood disorders.
They say the findings are important for understanding the causes and improving the treatment of depression.
Scientists are already aware that many people with depression have high levels of cortisol, a human stress hormone, but it has always been unclear whether that was a cause or effect.
This study appears to show that long-term exposure to cortisol exacerbates the symptoms of depression.
Researchers Paul Ardayfio, BSC, a graduate student in molecular neurobiology, and Kwang-Soo Kim PhD made their discovery by exposing mice to both short-term and long-term durations of the stress hormone in rodents, corticosterone.
In the study the researchers gave 58 mice the hormone in drinking water so as not to confuse the results with the stress of injection.
Chronic doses were 17 to 18 days of exposure; acute doses were 24 hours of exposure.
The mice were put through two tests; in one mice in a dark part of a cage got the chance to explore a bright, open part of a cage and it was found that the mice that drank the spiked water on a daily basis were more hesitant to enter the exposed space. The researchers interpreted that hesitancy as anxiety.
In the other test, the researchers exposed the mice to a high-frequency sound and the mice under constant corticosterone exposure rather than having an exaggerated reaction had a dulled reaction to that sound the first 10 times they heard it.
It suggests that constant exposure to the stress hormone may have depressed the mice, dimming immediate reactions and left them less able to handle a stressful event.
The authors believe this is the first experiment to compare the effects of chronic corticosterone with the effects of acute corticosterone on anxiety-like behavior.
Other evidence has linked depression and anxiety to a disruption in the hormonal system so the findings are not a complete surprise.
Fifty percent of those with Cushing's disease, where the adrenal system releases too much cortisol, have depression and anxiety and the "anxious-retarded" subtype of depression is commonly associated with disruption of that same hormonal system.
People receiving corticosteroid therapy for inflammatory and other disorders have increased mood-related side effects, including anxiety and depression and higher glucocorticoid levels for chronic periods have been linked to increased activity in anxiety-related brain regions such as the amygdala in both rodents and humans.
All the evidence points to the fact that stress hormones cause anxiety, which appears with depression.
The authors conclude that chronically high levels of cortisol has detrimental effects on the brain and on behavior and this relationship may help researchers to design new psychiatric drugs that treat the causes of disease rather than the symptoms.
The research can be seen in the April issue of Behavioral Neuroscience, published by the American Psychological Association.