DESCRIPTION (provided by applicant): Eating disorders (EDs) affect approximately 5% of the population and have a variety of adverse effects on mental and physical health. The treatment of disordered eating has progressed in recent years but further progress will depend in part on improving the field's understanding of eating disorder psychopathology. The cognitive-behavioral therapy (CBT) model of EDs has garnered substantial support but this framework does not sufficiently address two domains that appear to have a major impact on disordered eating. We call the first domain Weight History, which consists of premorbid body mass, the discrepancy between highest ever and current body weight (weight suppression, WS) and current BMI (which is often at very low, unhealthy levels). We have shown that WS and BMI (and their interaction) are robust predictors of many ED characteristics and that these relationships are not sufficiently accounted for by the CBT model. The second domain involves brain reward and inhibitory responses to palatable food cues. Evidence indicates that a continuum exists, with the poles anchored by the opposing responses to food cues of restricting anorexic patients and overweight binge eaters (with the former showing reward hypo-activation and inhibitory hyper-activation and the latter showing the reverse). Yet little known about how these abnormal patterns contribute to ED psychopathology. Because the variables comprising both domains are continuous in nature, and because the current application will study ED individuals regardless of DSM diagnosis, the proposed research is consistent with RDoC recommendations. We test the hypotheses that the two domains will be cross-sectionally related to eating disorder psychopathology, will predict future weight gain, ED symptomatology and course and that brain activation in reward and inhibitory regions of interest will mediate the predictive effects of Weight History variables on weight change and ED outcomes. These hypotheses will be tested among 96 ED individuals receiving treatment in any level of outpatient care. At baseline they will be assessed using standardized measures of Weight History and ED psychopathology and will undergo structural and functional MRI using a paradigm aimed at measuring their reward and inhibitory activation to food pictures in regions of interest. The measures of weight and ED symptomatology will be repeated at 3 and 6-month follow-ups. The proposed research has substantial potential to identify new sources of ED psychopathology that can be translated into novel treatments for these treatment-resistant disorders.

PUBLIC HEALTH RELEVANCE: Weight History, Brain Activation to Food Cues and Eating Disorder Psychopathology Eating disorders are a serious mental and physical health problem. Weight history and abnormal activation in brain reward and inhibitory areas appear to be related to ED psychopathology. This study will examine fMRI-assessed brain reward and inhibitory areas and weight history variables to predict, cross-sectionally and prospectively, ED psychopathology. Results will support development of novel treatments for these treatment-resistant disorders.