Key PointsQuestionHow does brain response in participants with adolescent anorexia nervosa (AN) compare with healthy controls during taste reward conditioning?FindingsIn this cross-sectional multimodal brain imaging study of 56 female adolescents and young adults with AN and 52 matched controls, the AN group showed hyperactivation in the caudate head, nucleus accumbens, and insula compared with controls during a classical conditioning paradigm that has been associated with dopamine function. Orbitofrontal brain response in the AN group was positively associated with harm avoidance and striatal-hypothalamic connectivity but negatively associated with change in body mass index during treatment.MeaningsAltered brain reward response in adolescent AN may indicate altered dopamine function, may have a key role in AN’s specific pathophysiology, and should be explored as a target for biological treatments.

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.

An eating disorder is a severe psychiatric illnesses with a complex biopsychosocial background. Brain imaging now allows study of the living human brain. Understanding the neurobiology of eating disorders holds promise for developing more effective treatments. New research enables the development of models for brain function and food avoidance.

Objective Finding medication to support treatment of anorexia nervosa has been difficult. Neuroscience based approaches may help in this effort. Recent brain imaging studies in adults and adolescents with anorexia nervosa suggest that dopamine related reward circuits are hypersensitive and could provide a treatment target. Method Here we present a retrospective chart review of 106 adolescents with anorexia nervosa some of whom were treated with the dopamine D2 receptor partial agonist aripiprazole during treatment in a specialized eating disorder program. Results The results show that aripiprazole treatment was associated with greater increase in body mass index (BMI) during treatment. Discussion The use of dopamine receptor agonists may support treatment success in anorexia nervosa and should be further investigated.

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