Association of Elevated Reward Prediction Error Response With Weight Gain in Adolescent Anorexia Nervosa

Abstract

Objective Anorexia nervosa is a psychiatric disorder of unknown etiology. Understanding associations between behavior and neurobiology is important in treatment development. Using a novel monetary reward task during functional magnetic resonance brain imaging, the authors tested how brain reward learning in adolescent anorexia nervosa changes with weight restoration. Method Female adolescents with anorexia nervosa (N=21; mean age, 15.2 years [SD=2.4]) underwent functional MRI (fMRI) before and after treatment; similarly, healthy female control adolescents (N=21; mean age, 16.4 years [SD=1.9]) underwent fMRI on two occasions. Brain function was tested using the reward prediction error construct, a computational model for reward receipt and omission related to motivation and neural dopamine responsiveness. Results Compared with the control group, the anorexia nervosa group exhibited greater brain response 1) for prediction error regression within the caudate, ventral caudate/nucleus accumbens, and anterior and posterior insula, 2) to unexpected reward receipt in the anterior and posterior insula, and 3) to unexpected reward omission in the caudate body. Prediction error and unexpected reward omission response tended to normalize with treatment, while unexpected reward receipt response remained significantly elevated. Greater caudate prediction error response when underweight was associated with lower weight gain during treatment. Punishment sensitivity correlated positively with ventral caudate prediction error response. Conclusions Reward system responsiveness is elevated in adolescent anorexia nervosa when underweight and after weight restoration. Heightened prediction error activity in brain reward regions may represent a phenotype of adolescent anorexia nervosa that does not respond well to treatment. Prediction error response could be a neurobiological marker of illness severity that can indicate individual treatment needs.

The Neurobiology of Eating Disorders

“…Brain activation predicted weight gain during treatment, but short-term weight restoration was not associated with normalization of brain response. 75,76 Those studies suggested heightened dopamine-related brain response that does not easily normalize with weight recovery. 76 In summary, altered reward circuits in AN may be associated with altered learning and brain dopamine function, and traits such as sensitivity to punishment could be predisposing.…”

The acceptability, feasibility, and possible benefits of a neurobiologically‐informed 5‐day multifamily treatment for adults with anorexia nervosa

“…Accumulating behavioral and neuroimaging evidence supports a neurobiologically‐based temperament that impacts the development and maintenance of AN—characterized by anxiety, reward insensitivity, perfectionism, altered interoceptive awareness, harm avoidance, and cognitive inflexibility (Fassino, Piero, Gramaglia & Abbate‐Daga, ; Harrison, O'Brien, Lopez, & Treasure, ; Lilenfeld, )—that is related to altered insula and fronto‐striatal neural circuit function (Berner et al, ; DeGuzman, Shott, Yang, Riederer, & Frank, ; Kerr et al, ; Oberndorfer et al, ; Wierenga et al, ). In addition to predating AN, mild to modest amounts of these traits often persist after recovery (Wagner et al, ), suggesting those who recover might do so by effectively managing these traits.…”

The partial dopamine D2 receptor agonist aripiprazole is associated with weight gain in adolescent anorexia nervosa

“…Neurobiological research from our group suggests that anorexia nervosa is associated with heightened responsiveness in brain reward circuits and this may be due to a hyper-sensitive dopamine system (DeGuzman, Shott, Yang, Riederer, & Frank, 2017; Frank, 2016b; Frank et al, 2012). The dopamine partial agonist aripiprazole is thought to down-regulate dopamine D2 receptor activity.…”