A Metabolic Perspective on Reward Abnormalities in Anorexia Nervosa

Anorexia nervosa (AN) is the psychiatric disorder with the highest mortality rate; however, the mechanisms responsible for its pathogenesis remain largely unknown. Large-scale genome-wide association studies (GWAS) have identified genetic loci associated with metabolic features it AN. Metabolic alterations that occur in AN have been mostly considered as consequences of the chronic undernutrition state but until recently have not been linked to the etiology of the disorder. We review the molecular basis of AN based on human genetics, with an emphasis on the molecular components controlling energy homeostasis, highlight the main metabolic and endocrine alterations occurring in AN, and decipher the possible connection between metabolic factors and abnormalities of reward processes that are central in AN.