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Prediction Error and Altered Dopamine Function May Play Key Role in Anorexia Nervosa

Prediction error brain response may play a key role in adolescent anorexia nervosa, driving anxiety and ventral striatal-hypothalamus circuit-controlled food avoidance, according to the results of a study published in JAMA Psychiatry.

Elevated harm avoidance has been found in patients with anorexia, particularly during the ill state, and is associated with poor treatment outcomes. Harm avoidance has been associated with availability of serotonin neurotransmitter receptors and binding of dopamine receptors in anorexia after recovery. Dopamine is important for food approach, and evidence from animal studies suggest that after food restriction, there is enhanced neuronal dopamine activation. Thus, it is postulated that brain circuits involving dopamine may be crucial in the pathophysiology of anorexia.

Guido K. W. Frank, MD, of the Department of Psychiatry at the University of Colorado Anschutz Medical Campus, School of Medicine, in Aurora, Colorado, and colleagues conducted a cross-sectional multimodal brain imaging study in 56 female adolescents and young adults with anorexia and 52 matched healthy control participants at a university brain imaging facility and eating disorder treatment program from July 2012 to May 2017.

The investigators set out to test the hypothesis that reward learning prediction error response would be elevated in anorexia and associated with harm avoidance. They wanted to determine how brain response in participants with adolescent anorexia compares with health controls during taste reward conditioning. The subjects participated in a sucrose-taste, classical conditioning paradigm, where violations of learned associations between conditioned visual and unconditioned taste stimuli resulted in dopamine-related prediction error. The investigators studied the dynamic effective connectivity during the sweet taste test to determine hierarchical brain activation across the network that regulates eating.

The altered brain reward response seen in adolescents with anorexia in this study may indicate alterations in dopamine function, which may play a key role in anorexia's pathophysiology. Essentially, in patients with anorexia, eating food triggered the neurotransmitter for dopamine to become more active, but unlike in healthy individuals, it also triggered anxiety, creating a vicious cycle of feeling anxiety about eating and restricting diet further.

The elevated prediction error response associated with brain dopamine activity is an adaptation to food restriction and weight loss that normalizes with long-term recovery.

The authors contend that these findings point to potential targets for biological treatment of this disorder. They call for longitudinal studies and neurotransmitter challenge studies to further our understanding of the mechanisms involved in disrupting or altering brain circuits in anorexia.