Exploring the Brain for Clues to Anorexia Nervosa

Low-activity areas of the brain
may be related to AN.

Dr. Laura M. Holsen and colleagues at Harvard had a novel idea–using advanced imaging technology to explore whether patients with anorexia nervosa (AN) have disrupted brain circuitry that interferes with normal appetite and satiety. The authors hypothesized that a causal factor for AN might be lower-than-normal levels of food motivation in appetite-controlling sections of the brain.

Dr. Holsen and colleagues used functional magnetic resonance imaging (fMRI) of the brain among women with active AN, a second group of women diagnosed with AN who were weight-restored, and a group of healthy controls (J Psychiatry Neurosci 2012; DOI: 10.1503/jpn. 11-156). Women with restricting-type AN (active AN group; n=12), and weight-restored women with a history of AN-restricting type or binge eating/purging type (weight-restored group; n=10) between the ages of 19 and 28 years were recruited. All met DSM-IV criteria for a diagnosis of AN. Eleven healthy women from the community who had regular menses, no pubertal delay, and who were currently at 90% to 110 % of ideal body weight (IBW) were added as a control group.

After a 12-hr fast, healthy controls and weight-restored women were studied during the follicular phase of their menstrual cycle (days 1-10). The first fMRI session was set for 8 am, and then participants were asked to consume a 400-kcal mixed meal standardized for micro- and macronutrient content over the course of 15 minutes. When the women finished eating, the staff weighed the portion of the uneaten meal to determine caloric intake. A second fMRI scan began at about 9:15 am. Immediately before and after their fMRI scanning sessions, the participants rated their hunger and desire to eat their favorite food, using visual analog scales and scored their current anxiety level using the State-Trait Anxiety Inventory. After each fMRI session, participants rated a selection of the food and nonfood stimuli on a scale ranging from highly unappetizing to highly appetizing. After the post-meal scan, participants also completed several questionnaires such as the Beck Depression Inventory and the Eating Disorder Examination Questionnaire.

Low-activity areas of the brain were identified

The women with active AN had significantly lower percentages of IBW than did the weight-restored and control groups. Women with active disease also had significantly greater eating disorder symptoms and higher levels of trait anxiety than did the weight-restored and control groups. Women in the control group had higher ratings of hunger and desire to eat their favorite foods than did women with active disease and, to a lesser degree, women in the weight-restored group. For women in the control group, high-calorie food was more appalling and appetizing than for the other groups. Women with active disease showed higher levels of state anxiety than did controls and weight-restored women both before and after scanning

The authors found hypoactivity in the hypothalamus, amygdala, and anterior insula in the weight-restored women compared to control women during periods when appetite was greatest; they believe this is compelling evidence that these low-activity areas of the brain may point to long-term physiological traits tied to AN. They added that the functions of these regions of the brain are not limited to appetite and food intake regulation, but are also highly involved in the response to stressful stimuli in healthy controls and have been implicated in anxiety disorder and obsessive-compulsive disorder.

Self-reported hunger and perception of the reward value of food are significantly altered in women with active AN, and debate continues about whether these abnormalities are driven by physiologic or psychologic processes. The authors add that even though weight gain through restoration of healthy eating patterns is the primary goal of treatment for patients with AN, disturbed eating behavior remains even after recovery. Thus, patients are always at risk of relapse. Evidence of possible  state and trait patterns of hypoactivation in food motivation in regions involved in appetite-related behavior underscore the importance of seeking out other potential state and trait characteristics when investigating brain phenotypes in persons with AN.