Roadblocks to Restoring Healthy Weight in Patients with Anorexia Nervosa

A small study highlights interference
with weight gain.

Although helping patients with anorexia nervosa (AN) regain weight by restoring healthy eating patterns one primary goal of treatment, researchers from three Boston medical centers report that the complex phenotype of AN often interferes with healthy weight gain.

Dr. Laura M. Holsen of Brigham and Women’s Hospital and Massachusetts General Hospital, Boston, and her colleagues designed a study comparing three groups: women with active AN, weight-restored women with AN, and a healthy-weight control group, in an attempt to better understand hedonic and nonhedonic aspects of hunger and satiety (J Psychiatry Neurosci 2012 Apr 3; 37(3):110156. doi: 10.1503/cjs.110156; epub ahead of print). Weight-restored women often show traces of abnormal eating behavior and other core diagnostic features of AN after gaining weight. Thus, the authors expected that the results for women who had regained weight would fall somewhere between those for women with active AN and those for healthy controls.

At the beginning of the study, all subjects fasted for 12 hours. Healthy controls and weight-restored women were tested during the follicular phase of the menstrual cycle (days 1-10). The first pre-meal functional magnetic resonance (fMRI) scans were done at 8 am. Then, over the course of 15 minutes participants consumed a 400-kcal mixed meal standardized for micro- and macronutrient content. When each participant finished eating her meal, the bionutrition staff weighed the food remaining, and established the exact caloric content. Immediately before and after each fMRI scanning session the participants rated their appetite using visual analogue scales, and also rated their anxiety level using the State-Trait Anxiety Inventory. In addition, the participants were asked to rate a selection of the food and nonfood stimuli using a scale from “highly unappetizing/unpleasant” to “highly appetizing/pleasant” using visual analogue scales. They also completed several study questionnaires, including the Spielberger State-Trait Anxiety Inventory, Eating Disorder Examination Questionnaire, and the Beck Depression Inventory.

Functional MRI scanning was also performed while participants viewed a selection of 100 high-calorie foods, including doughnuts, pizza, and potato chips, and then 100 low-calorie foods, such as fruit and grilled fish, and finally 100 nonfood items (for example, common household objects).

Differences emerged among the groups

The final study group included 12 women with restricting-type AN, 10 weight–restored women (8 with restricting-type AN and 2 with binge-eating/purging type AN), and a control group of 11 healthy-weight women. The women with active disease had significantly lower percent ideal body weight (%IBW) than did the weight-restored and control women. By design, the women with active disease had significantly greater eating disorder symptoms and trait anxiety symptoms than did weight-restored and control women.

There were no differences in overall caloric intake during breakfast, indicating that differences in brain activity during the post-meal session could not be attributed to differences in caloric intake. Compared with the controls, women with active AN showed pre-meal hypoactivation in several areas of the brain, including the hypothalamus, amygdala, hippocampus, orbitofrontal cortex, and anterior insula, and post-meal hypoactivation in the amygdala and insula. After the meal, hypoactivation in the anterior insula persisted in women with active AN. After controlling for %IBW, pre-meal differences remained significant in the anterior insula and showed a trend toward significance in the amygdala. There were no differences in post-meal brain activation between controls and weight-restored women. Differences between women with active disease and weight-restored women were noted only after the meal: compared with the weight-restored women, those with active disease showed amygdala hyperactivation and anterior insula hypoactivation.

The systematic hypoactivation in the hypothalamus, amygdala, and anterior insula among the women with active AN and in weight-restored women compared with healthy-weight controls measured during a state of high motivation (pre-meal), suggested that these deficits might be enduring traits of AN. During a period of low motivation after the meal, anterior hypoactivation persisted among women with active disease (but not in weight-restored women) compared with controls, suggesting that insula deficits might also reflect a clinical state of AN, with restored ability to regulate appetitive signals following food intake after recovery.

One important finding, according to the authors, was that anterior insula and amygdala hypoactivation in both AN groups before the meal were independent of body weight, providing additional evidence that among women with active disease, such deficits were not associated with low weight or starvation. Activation in the hypothalamus, amygdala and anterior insula in controls and in weight-restored women were significantly associated with behavioral indicators of hedonic aspects of appetite; these relationships were not present in women with active disease. Thus, the abnormal brain response in these regions and in the hypothalamus during a state of hunger and high appetitive motivation may persist after weight is restored. The authors also reported that hypoactivation in response to high-calorie foods in the hypothalamus pre-meal in women with active disease and in weight-restored women, which to their knowledge has not been reported before, might be related to well-established neuroendocrine abnormalities in individuals with AN.

According to the authors, the evidence of potential state and trait patterns of hypoactivation of food motivation regions in the brain that are involved with appetite, assessment of food reward, and integration with interoceptive signaling of one’s internal state of well-being and homeostatic and hedonic aspects of appetite, are reminders of the importance of examining state-trait characteristics when brain phenotypes are being studied in individuals with AN.