Bad Memories Not Necessarily Forever

Megan Brooks

May 31, 2011 — Bad memories aren't necessarily forever. Canadian researchers have shown that using metyrapone to lower cortisol levels before recalling a negative memory can lessen the emotional strength of that memory, with lasting effects, while leaving neutral memories intact.

"This study shows that even if you have a bad memory engraved in your brain for a while, you may have a second window of opportunity to change it," Marie-France Marin, a PhD student from the Centre for Studies on Human Stress of Louis-H. Lafontaine Hospital, University of Montreal, Quebec, Canada, told Medscape Medical News.

Ms. Marie-France Marin

She is hopeful that, with further study, this finding may eventually help individuals with posttraumatic stress disorder (PTSD).

"People with PTSD have memories that preclude them from leading a normal life. If we can decrease emotional memories for these people, this has a lot of implications, particularly in people for whom PTSD therapies do not work or are not optimal," she said.

"If we can combine therapy with lowering cortisol levels, this might help them alter the traumatic memory trace and ease the process. We are not there yet, but this is a first step," Ms. Marin added.

The study was published online May 18 in the Journal of Clinical Endocrinology and Metabolism.

Finding New but Not Unexpected

Cortisol is a stress hormone involved in memory recall. For a long time, it was thought that once a memory was formed in the brain, it could not be changed. Animal studies challenged this theory by showing that every time a memory is recalled, the memory trace is unstable and it can be altered.

It's known that cortisol can modulate the process of memory retrieval. Tony Buchanan, PhD, assistant professor, Department of Psychology, Saint Louis University, Missouri, who was not involved in the research, said the findings by Ms. Marin and colleagues are new "but not unexpected."

"What has been shown in the past is the enhancing effects of cortisol on emotional memory. The new bit here is the ability to reduce negative memories specifically by reducing cortisol levels," he told Medscape Medical News.

Ms. Marin and colleagues assessed the effect of cortisol inhibition on retrieval of neutral and emotional memory using the drug metyrapone, which significantly decreases cortisol levels.

Thirty-three healthy men watched a computer-narrated story composed of neutral and emotionally negative events. Three days later, the men were divided into 3 groups and given a single 750-mg dose of metyrapone, a double dose of metyrapone (750 mg followed by 750 mg 3 hours later), or placebo. They were then asked to recall as much information as possible from the story at a time when the metyrapone group's cortisol levels were expected to be at their lowest.

According to the researchers, men in the group who received double-dose metyrapone recalled significantly less emotional material from the story than men in the other 2 groups; "they had less emotional memory of the story," Ms. Marin said.

"Surprisingly," she added, the decreased memory of negative information was still present 4 days later when cortisol levels had recovered. No acute or long-term effects of metyrapone were observed in recalling the neutral parts of the story.

Strong Indication of Neural Change

"The key strength," Dr. Buchanan said, "is the finding that these effects persist 4 days after metyrapone was administered. That's a pretty strong indication that a neural change has occurred and it's not just some side effect of the presence of the drug in the system."

Dr. Buchanan added that this strategy is potentially useful in the clinical setting but more research is needed.

Ms. Marin and colleagues agree. Although the results have "clear" potential for pharmacologic easing of painful memories in patients with PTSD, the study was not performed in traumatized individuals, and it remains to be seen whether similar results can be achieved.

In addition, metyrapone is no longer commercially marketed, but other compounds are known to decrease cortisol levels, and "it remains to be seen whether other compounds have the same effect," said Ms. Marin.

It will also be important to replicate these findings in women, "given that some studies report important sex differences in response to catecholamine or cortisol modulation on memory traces," the researchers write.

It's also important to note that metyrapone likely changes the concentrations of other hormones besides cortisol; therefore, it's not possible to conclude for certain that the observed effects could be explained only by lowering cortisol concentrations.

"By using different compounds and by measuring multiple hormones, future studies will be able to better understand the exact mechanism underlying the current results," the researchers note.

The study was supported by the Canadian Institutes of Health Research. The study authors and Dr. Buchanan have disclosed no relevant financial relationships.

J Clin Endocrinol Metab. Published online May 18, 2011.Abstract