Molecular Endocannabinoid Mediators of Impaired Aversive Learning in Low Weight Eating Disorders

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Project summary: Low weight eating disorders (LW-EDs), including anorexia nervosa and related atypical variants, are characterized by persistent food avoidance. Disturbances in behavior among individuals with LW-EDs persist beyond the acute starvation stage into the period of weight normalization, with abnormalities observed in food- cue learning, expectancies related to food, and food choice. We hypothesize that the persistence of disordered affect and food-cue learning result from an allostatic disruption of endocannabinoid (eCB) tone, as specifically evidenced by an upregulation of eCB1 receptors and an impaired responsivity and tone of eCBs. This proposal therefore aims to test this theory using the novel PET ligand [(18)F]MK-9470, a robust and reliable measure of brain eCB1 receptor availability in 6 women recently weight restored from a LW-ED and 6 age, gender, and body mass index matched control women. Participants will complete behavioral measures of food-cue learning and food choice, PET measures of CB1 receptor availability, time course changes in plasma eCBs to a palatable food challenge, and objective and subjective measures of eating behavior. We will: (1) model both region specific and whole brain measures of eCB1 receptor availability, and (2) test whether eCB1 receptor discriminates those with LW-EDs from healthy controls. Further, we will evaluate if this upregulation mediates impaired time course response of plasma eCBs to food challenge. Results from this study will provide critical data about the unique role of eCBs in pathological patterns of food choice and avoidance in those with LW- EDs. Successful completion of this study will offers a tangible and robust target for novel treatment intervention with pharmacological, nutritional, or combination therapeutics among those with LW-EDs.