March 20, 2020
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Neural circuitry findings 'open the door' to new anorexia nervosa treatments

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Walter H. Kaye

Neural circuitry dysfunction may be associated with prolonged periods of extremely restricted food intake and food avoidance among patients with anorexia nervosa, according to study results published in American Journal of Psychiatry.

“There is a powerful biological mechanism contributing to restricted eating and weight loss in anorexia nervosa,” Walter H. Kaye, MD, founder and executive director of the Eating Disorders Program at University of California, San Diego, told Healio Psychiatry. “These individuals appear to have impaired drive and ability to initiate eating in part related to anxiety. From animal and human studies, we know much about the brain circuity that regulates eating, and these findings in anorexia nervosa are within this circuitry and make sense from a scientific perspective.”

Although some research has shown that those with anorexia nervosa exhibit alteration in neural mechanisms coding salience, motivation and valuation of food when ill and following weight restoration, few studies in this patient population have systematically examined whether functioning is altered in this circuitry during periods of hunger that may persist after recovery. Gaining insight into the mechanisms that contribute to the neurobiology of self-starvation in anorexia nervosa could allow researchers to identify new treatment targets, such as through the use of neuroimaging to measure brain responses to palatable tastants, including sucrose.

To examine potential neural insensitivity to the effects of food avoidance and extreme dietary restriction in anorexia nervosa, Kaye and colleagues administered sucrose solution or ionic water at two functional MRI scanning sessions scheduled 24 hours apart, one after a standardized meal and one after a 16-hour fast. They acquired MRI data of 26 women who were in remission from anorexia, to avoid the confounding effects of malnutrition, and 22 matched control women. The investigators compared groups across conditions on task-based functional connectivity and blood-oxygen-level-dependent (BOLD) signal and task-based connectivity within a network of interest responsible for transforming taste signals into motivation to eat and food valuation.

Across the two groups, participants exhibited similar BOLD responses to water and sucrose tastants. Hunger had opposite effects on tastant response in the remitted anorexia nervosa group and control group, according to a group-by-condition interaction in the ventral caudal putamen. Further, it indicated an increase and a decrease, respectively, in BOLD response when hungry. Compared with the control group, those in the remitted anorexia nervosa group exhibited a similar opposite effect of hunger on insula-to-ventral caudal putamen functional connectivity. Exploratory analyses revealed an association between lower caudate response to tastants when hungry and higher scores on harm avoidance among participants in the remitted anorexia nervosa group.

“These findings open the door to new strategies or medications that may be more successful in improving eating behavior in anorexia nervosa,” Kaye told Healio Psychiatry. “I have been treating patients with anorexia nervosa for many years and have been frustrated by the high rate of relapse and death. Eating makes people with anorexia nervosa very anxious and now we finally have good insights into why these symptoms occur. I am optimistic this will lead to more effective treatment.” – by Joe Gramigna

Disclosures: The authors report no relevant financial disclosures.