Radically Altered Brain Reward Circuits Characterize Anorexia, Study Finds

A team of researchers at the University of Colorado has developed a model of how self-induced starvation may trigger alterations in the brains of people with anorexia nervosa that drive food avoidance and thus perpetuate the disorder.

The research, led by Guido Frank, M.D., was posted July 19 in JAMA Psychiatry. Frank is an associate professor of psychiatry at the University of Colorado School of Medicine in Denver with a specialty in the neurobiology of eating disorders.

The findings suggest that those with anorexia are negatively conditioned to sweet taste. This correlates with harm avoidance (a personality trait characterized by excessive anxiety and fear), the drive to thinness, and body dissatisfaction—behaviors that correlate with starvation-induced brain changes in the brain’s reward system.

The researchers devised a model employing brain imaging to measure the association between brain reward learning response in people with anorexia and treatment outcome as measured by weight gain, elevated harm avoidance, and activation of the brain’s neural reward circuits. The five-year study was conducted with 56 females aged 11 to 21 with anorexia and 52 healthy matched controls.

All subjects were conditioned to associate either getting or not getting a sugar solution—a reward—with a specific shape; brain imaging was used to see how they responded when their expectations were either fulfilled or violated. This expectation—measured as “prediction error”—evaluates the difference between received and predicted rewards and is associated with dopamine release. If people expect—and receive—a reward, there is no prediction error. If they anticipate but don’t receive the reward, there is negative prediction error, and if they do not expect the reward but receive it, there is positive prediction error.

Subjects with anorexia had a significantly greater response to prediction error than healthy controls, whether it involved unexpectedly getting or not getting the sugar solution. This response was indicated by enhanced dopamine release and by brain scans showing higher activation of neural reward circuits. Sweet taste stimulates dopamine release and activation across the neural reward circuits, which typically promotes eating in healthy people. This study, however, suggests that the adolescents may have developed an inverse association with dopamine release across the larger reward circuitry.

Subjects with anorexia also displayed higher cortisol levels compared with controls. Cortisol is associated with stress and anxiety, and the authors speculated that this further drives abnormally strong prediction error response and suppresses eating. As the process progresses, “it becomes a downward spiral, and they cut out more and more,” said Frank.

“I think this change of the brain during food restriction is probably a normal adaptation in general and that the reward system gets more sensitized in times of food scarcity,” said Frank. But for reasons that are not yet understood, some people sensitize more quickly or more strongly than others, which is reinforced by how they think about the relationship between eating and health. The brain imaging revealed that in those with anorexia, the reward circuits were activated in a direction that indicated that how the subjects were thinking was overriding the typical drive to eat—opposite the direction in healthy controls.

The finding that the neural reward circuits in subjects with anorexia react differently from those of the controls to receipt or deprivation of a taste reward strengthens support for the idea that starvation profoundly alters the brain’s dopamine-linked reward system, commented Joanna Steinglass, M.D., in an accompanying editorial. But the precise meaning of these findings remains a challenge, she added. Steinglass is an expert in the study and treatment of eating disorders in the Columbia University Department of Psychiatry.

Carrie McAdams, M.D., Ph.D., is a psychiatrist and neuroscientist at the University of Texas Southwestern Medical Center specializing in the treatment of adult eating disorders. What she finds exciting about Frank’s study, she told Psychiatric News, was the innovative use of fMRI. Brain imaging allows scientists to get past the issue of patient subjectivity and figure out “what’s really happening in the neurocircuitry,” she added.

“It is very clear that the process of starvation has really profound effects on the body,” said McAdams. Everyone with anorexia has experienced starving, “and that process of starving can change the brain.” The problem is the “chicken or egg—we don’t know whether the problems in the brains of people with anorexia are because they went through starvation or if there is some pre-existing thing that led to their developing the illness.” ■

“Association of Brain Reward Learning Response With Harm Avoidance, Weight Gain, and Hypothalamic Effective Connectivity in Adolescent Anorexia Nervosa” can be accessed here.