Even after more than a year of maintaining a normalized body weight, young women who recovered from anorexia nervosa show vastly different patterns of brain activity compared to similar women without the eating disorder, Walter H. Kaye, M.D., professor of psychiatry, University of Pittsburgh School of Medicine, and colleagues report in the December issue of the American Journal of Psychiatry.

Studying these differences in brain function could lead to a better understanding of why some young women, who are typically worriers and perfectionists in childhood, are at greater risk of developing the disorder. Evidence also shows that such patterns of temperament persist even after recovery.

“Functional magnetic resonance imaging (fMRI) of the brain is providing new clues to why people with anorexia nervosa are able to deny themselves food and other immediately rewarding pleasures,” said Dr. Kaye, who is director of the eating disorders research program at Western Psychiatric Institute and Clinic of the University of Pittsburgh Medical Center (UPMC) and has a joint appointment as professor of psychiatry at the University of California, San Diego. “In addition, we have a new understanding of why people with anorexia seem to worry so much.”

Dr. Kaye and his colleagues studied 13 women who had recovered from anorexia, maintaining a normal weight and regular menstrual cycles for at least one year, and 13 healthy women in a control group. Each was asked to guess whether a flashing question mark on a computer screen represented a number higher or lower than five. Correct guessers were rewarded with $2, while incorrect guessers forfeited $1. Brain activity in the anterior ventral striatum and caudate regions were monitored during game play with fMRI brain imaging. The anterior ventral striatum is associated with instant emotional responses, while the caudate is involved in linking actions to outcome and planning.

“During the game, brain regions lit up in different ways for women who formerly had anorexia compared to healthy controls. While the brain region for emotional responses showed strong differences for winning and losing in healthy women, women with a past history of anorexia showed little difference between winning and losing,” said Angela Wagner, M.D., University of Pittsburgh School of Medicine and the study’s first author. “For anorexics, then, perhaps is it difficult to appreciate immediate pleasure if it does not feel much different from a negative experience.”

The caudate regions of the brains of formerly anorexic women, however, were more active than those of healthy controls, especially in the most anxious people, suggesting that women with a history of anorexia were more focused on the consequences of their choices, Dr. Kaye noted, adding that anorexics “tend to worry about the future” and doing things right.

“There are some positive aspects to this kind of temperament,” he said. “Paying attention to detail and making sure things are done as correctly as possible are constructive traits in careers such as medicine or engineering.” Carried to extremes, however, such obsessive thinking can also be harmful, Dr. Kaye added.

Results of the guessing game are instructive because they show that healthy women responded to wins and losses by “living in the moment” and moving on to the next task, while people with a past history of anorexia had trouble letting go. “They tended to try and find strategies within the game, and were concerned about making mistakes,” said Dr. Kaye.

There is no proven treatment that reverses symptoms in anorexia nervosa, which has the highest mortality rate of any psychiatric disorder. Increasing researchers’ understanding of these basic brain differences could influence future development of drugs and other treatments for anorexia, Dr. Kaye added. “We’re starting to understand these processes because we have better tools, such as brain imaging, and a better understanding of how the brain works due to advances in cognitive neuroscience.”

Additional study authors are Howard Aizenstein, M.D., Ph.D.; Vijay K. Venkatraman, M.S., Laura Mazurkewicz, B.S.; Ursula F. Bailer, M.D.; Lorie Fischer, B.S.; J. Christopher May, M.D.; Julie Fudge, M.D.; Guido K. Frank, M.D.; Van Nguyen, M.D., Cameron Carter, M.D.; and Karen Putnam, M.S.

The study was funded by the National Institute of Mental Health and the Price Foundation.