Abstract
Anorexia nervosa (AN) and atypical AN (AtypAN) are complex neurobiological illnesses that typically onset in adolescence with an often treatment-refractory and chronic illness trajectory. Aberrant eating behaviors in this population have been linked to abnormalities in food reward and cognitive control, but prior studies have not examined respective contributions of clinical characteristics and metabolic state. Research is needed to identify specific disruptions and inform novel intervention targets to improve outcomes. Fifty-nine females with AN (n = 34) or AtypAN (n = 25), ages 10-22 years, all ≤90% expected body weight, and 34 age-matched healthy controls (HC) completed a well-established neuroimaging food cue paradigm fasting and after a standardized meal, and we used ANCOVA models to investigate main and interaction effects of Group and Appetitive State on blood oxygenation level-dependent (BOLD) activation for the contrast of exposure to high-calorie food images minus objects. We found main effects of Group with greater BOLD activation in the dorsal anterior cingulate cortex (dACC), dorsolateral prefrontal cortex (DLPFC), hippocampus, caudate, and putamen for AN/AtypAN versus HC groups, and in the three-group model including AN, AtypAN, and HC (sub-)groups, where differences were primarily driven by greater activation in the AtypAN subgroup versus HC group. We found a main effect of Appetitive State with increased premeal BOLD activation in the hypothalamus, amygdala, nucleus accumbens, and caudate for models that included AN/AtypAN and HC groups, and in BOLD activation in the nucleus accumbens for the model that included AN, AtypAN, and HC (sub-)groups. There were no interaction effects of Group with Appetitive State for any of the models. Our findings demonstrate robust feeding-state independent group effects reflecting greater neural activation of specific regions typically associated with reward and cognitive control processing across AN and AtypAN relative to healthy individuals in this food cue paradigm. Differential activation of specific brain regions in response to the passive viewing of high-calorie food images may underlie restrictive eating behavior in this clinical population.