Studies in animal models help scientists identify systems that may induce vulnerability to eating disorders, and aid in pinpointing brain consequences of behaviors that underpin anorexia nervosa.

For nearly a dozen years, psychiatry researchers at Johns Hopkins have been studying behavioral and neurological changes related to anorexia using the activity-based anorexia, or ABA, model in young female rats. Some lessons learned in these animals are being applied to clinical research in search of better understanding and management of the condition for patients.

There is a dearth of information about the neurobiology of anorexia, which can make treatment challenging, says Kimberly Smith, assistant professor of psychiatry and behavioral sciences: “Using the ABA model, we can begin to shed light on that underlying neurobiology and can answer questions such as: Does anorexia change neural circuitry? Does it change physiology? What’s going on in the brain or in the body that may maintain the disorder? Through such inquiries, we may begin to identify treatment targets.”

The ABA model gives rats free access to a running wheel and restricted time for food intake. Studies over the years have indicated that rats exposed to the program can rapidly acquire alterations in taste and restricted food preferences, increased anxiety and lower circulating levels of some antioxidants, among other changes, says Timothy Moran, director of Johns Hopkins’ Behavioral Neurosciences Laboratory.

The work “has helped identify brain systems that might induce a vulnerability to eating disorders, Moran says, “and it has identified brain consequences of engaging in the kind of behaviors that underlie anorexia nervosa.”

One study directed by psychiatry researcher Kellie Tamashiro and Angela Guarda, director of the Johns Hopkins Eating Disorders Program, is looking at levels of an appetite-stimulating peptide called agouti-related peptide, also known as AgRP, in patients with anorexia. Previous work by Tamashiro’s lab demonstrated that rats who passively reacted to stress induced by the ABA model had less AgRP and were more vulnerable to weight loss. The current study compares circulating levels of AgRP in the blood of patients with anorexia at the time of hospital admission and again after their weight has been restored. The researchers will look at hypothalamic regions of the brain controlling hunger using MRI to identify if the hormone is associated with greater disease severity.

“This could be the first clear identification of something that might not be simply a response to anorexia nervosa, but may be a predisposing factor,” says Moran, a coinvestigator.

Building on that work, Smith, another coinvestigator, has started her own study funded by the National Institute of Mental Health to compare eating-related anxiety in people with and without anorexia, and if that changes following treatment. The work includes using functional MRI to identify any underlying brain differences when participants are shown pictures of high calorie-density foods such as a donut or low calorie-density foods such as strawberries, and asked how comfortable they would be eating those items. Results in the first few patients indicate that anxiety is lessened after meal-based behavioral treatment, when patients are restored to a healthy weight.