Abstract
BACKGROUND: Anorexia nervosa (AN) is an often-chronic illness, and we lack biomarkers to predict long-term outcome. Recent neuroimaging studies using caloric taste stimuli suggest that paradigms that have tested conditioned neural responses to expectation or salient stimulus receipt may underpin behaviors. However, whether activation of those neural circuits can predict long-term outcome has not been studied. METHODS: We followed women treated for AN (n = 35, mean age [SD] = 23 [7] years) and tested whether functional imaging brain response during a taste conditioning paradigm could predict posttreatment body mass index (BMI). We anticipated greater neural activity relative to caloric stimulus expectation and that dopamine-related receipt conditions would predict lower posttreatment BMI, indicating fear-associated arousal. RESULTS: Follow-up occurred at mean (SD) = 1648 (1216) days after imaging. Stimulus expectation in orbitofrontal and striatal regions and BMI and BMI change at follow-up were negatively correlated, and these correlations remained significant for the right superior orbitofrontal cortex and BMI change after multiple comparison correction (r = -0.484, p = .003). This relationship remained significant after including time between brain scanning and follow-up in the model. Reward prediction error response did not predict long-term BMI. CONCLUSIONS: The orbitofrontal cortex is involved in learning and conditioning, and these data implicate this region in learned caloric stimulus expectation and long-term prediction of weight outcomes in AN. Thus, conditioned elevated brain response to the anticipation of receiving a caloric stimulus may drive food avoidance, suggesting that breaking such associations is central for long-term recovery from AN.