Brain Function Changes Associated With Anorexia Relapse

Women with anorexia nervosa, even those who have recovered and have maintained normal weight for more than a year, have persistent abnormalities in brain function that might explain the high relapse rate for this disorder, according to a study published in the December 2007 American Journal of Psychiatry.

In the first fMRI brain study to compare women who have recovered from anorexia with healthy controls, researchers from the University of Pittsburgh found that the women with past anorexia had an impaired ability to differentiate between “winning” and “losing” in a guessing game (coupled with reduced activation in the anterior ventral striatum) and excessive firing of circuits in the caudate.

“The lack of difference in brain activity between winning and losing conditions suggests that these women continue to [underappreciate] immediate pleasure, and so [they] might not experience the positive feelings associated with food,” lead author Angela Wagner, MD, told NeuroPsychiatry Reviews. “The high activity in the caudate probably reflects a heightened attempt to control the test situation. Unlike the normal controls, the anorexic women still thought they could find a way to control the outcome of the psychological challenge, even though this was impossible.”

DIFFERENTIATING POSITIVE AND NEGATIVE FEEDBACK

The investigators studied 13 women who had recovered from anorexia (all of whom were of normal weight and had regular menstrual cycles for at least one year) and 13 healthy women. The minimum recovery time was one year; one patient had maintained a normal weight for 10 years.

Each participant was asked to guess whether a flashing question mark on a computer screen represented a number higher or lower than 5. Participants who made correct guesses won $2, and incorrect guesses required participants to forfeit $1.

“During the game, brain regions lit up in different ways for women who formerly had anorexia, compared with healthy controls,” reported Dr. Wagner. “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. For anorexic women, then, perhaps it’s difficult to appreciate immediate pleasure if it does not feel much different from a negative experience.”

Conversely, the caudate regions in the formerly anorexic women were much more active during the game, compared with those areas in healthy controls. Dr. Wagner suggested that the women with a history of anorexia were focused excessively on the consequences of their choices. She noted that women with anorexia tend to worry a great deal about the future and to be overly anxious and obsessive about doing things in the “right” way. “The former anorexics were always looking for rules where there were none,” Dr. Wagner said.

The investigators believe that the results of this study indicate that healthy women respond to wins and losses by “living in the moment” and moving on to the next task. However, the women with a history of anorexia were unable to do this.

A BIOLIGICAL BASIS TO ANOREXIA

“Our study shows a biological background to the disease of anorexia nervosa,” commented Dr. Wagner. “It is not just a result of environmental influences. In the past, our approach as clinicians was to focus on behavior and on getting patients to eat. The functional studies suggest that perhaps we should also focus on mindset, on finding ways to train these patients to accept change and to experience pleasure. A logical next step also would be to study neurotransmitters, especially dopamine, and try to understand the differences we identified in brain circuits. This might, in turn, point the way to a new approach to pharmacologic therapy for anorexia nervosa.”

—Janis Kelly

Suggested Reading
Wagner A, Aizenstein H, Venkatraman VK, et al. Altered reward processing in women recovered from anorexia nervosa. Am J Psychiatry. 2007;164(12):1842-1849.

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