June 17, 1999 St. Louis, June 15, 1999 -- If it's been a really, really tough week at work and you can't remember where you put your car keys, it may be that high levels of the stress hormone cortisol are interfering with your memory. In the June Archives of General Psychiatry, investigators at Washington University School of Medicine in St. Louis provide the first direct evidence that several days of exposure to cortisol at levels associated with major physical or psychological stresses can have a signifcant negative effect on memory.
"We tested memory and other cognitive functions before treatment, after one day of treatment and again after four days, in individuals receiving either a high dose of cortisol, a lower dose or an inactive substance," explained lead author John W. Newcomer, M.D., assistant professor of psychiatry and psychology. "We saw memory impairment only in the individuals treated with the higher dose and only after four days of exposure. The good news is it appears that it would take several days of stresses like major surgery or severe psychological trauma in order for cortisol to produce memory impairment. And after a one-week wash-out period, memory performance returned to the untreated levels."
Cortisol is produced in the body during stress. It belongs to a family of stress hormones called glucocorticoids that, among other actions, can interfere with energy supply to certain brain cells involved in memory. Newcomer's previous work showed that treatments with a synthetic glucocorticoid called dexamethasone impaired memory. But this is the first study to demonstrate that prolonged exposure to high levels of cortisol--the hormone actually produced in the body in response to high stress-- has that same negative effect.
"The dexamethasone work came pretty close to telling the story of what actually happens with large amounts of stress and high levels of cortisol," Newcomer said. "But this study more accurately represents the effects of cortisol in the brain when a person is under high levels of stress."
A total of 51 people participated in the study -- 25 men and 26 women between ages 18 and 30. They were assigned to one of three groups. One group of seven men and eight women received a high daily dose of cortisol. A second group of eight men and eight women took a lower dose, and the remaining 10 men and 10 women received an inactive substance. All took their capsules twice daily for four days. The amounts mimicked cortisol levels secreted in response to stressful medical procedures. The high dose corresponds to cortisol secretion after events like abdominal surgery. The lower dose was similar to cortisol secretion during a minor medical procedure such as getting stitches or having a skin growth removed.
The volunteers also were asked to listen to and recall parts of a paragraph so the researchers could assess their verbal declarative memory. This type of memory involves several brain regions, including the hippocampus, a seahorse-shaped brain structure related to memory and learning. The memory test, as well as tests of other cognitive functions, were given before the cortisol treatment, after one day of treatment, after four days of treatment and six days after the subjects stopped taking cortisol.
Newcomer, who also is a staff psychiatrist at Barnes-Jewish Hospital, found that memory performance suffered only in those subjects who received the high dose of cortisol and only after the subjects had received the hormone for several days. Fourteen of the 15 individuals taking the high dose experienced a decrease in memory performance after four days of treatment. No effects were found on the other cognitive tests.
In addition to explaining the memory problems that could occur during hospitalizations for surgery, the results may be relevant to other situations as well, Newcomer said. Major psychological stresses, which can be different for different individuals, also could produce similar effects on memory. For example, if a student studying for a test has just experienced a major trauma such as a death in the family, he or she might not be as efficient at learning new material.
A few people may experience high cortisol levels in response to less profound events, such as the pressure of upcoming final exams. So Mom and Dad may have been right when they told us cramming for exams is not a good idea. "These high cortisol levels are relevant to the kind of memory that helps us function moment-to-moment," Newcomer said.
The remaining questions involve how much stress must be present before memory suffers. The cortisol levels produced in the study were significantly higher than those that occur during an average bad week. Most people would have to experience a severe medical situation or severe physical or psychological trauma. But Newcomer believes there may be some effects from long-term exposure to slightly lower levels, though those experiments have not yet been done.
The glucocorticoid effects on memory appear to be reversible. Therefore, Newcomer does not believe the memory effects demonstrated in this study are part of any process associated with loss of neurons or permanent damage in the hippocampus or other brain structures.
"The evidence suggests that these kinds of cortisol levels are not neurotoxic themselves," Newcomer said. "Perhaps sustained, high levels make neurons vulnerable to other types of injury, but we don't believe the memory impairments we saw in this study are in any way associated with an irreversible process. In fact, our evidence shows that this memory impairment is quickly reversible."
Newcomer JW et al. Decreased Memory Performance in Healthy Humans Induced by Stress-Level Cortisol Treatment. Archives of General Psychiatry, vol. 56, no. 6, pp. 527-533, June 1999.
This work was supported by grants from the National Institute of Mental Health and the U.S. Public Health Service.
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