BIOMARKERS OF WEIGHT CHANGE IN ANOREXIA NERVOSA



 DESCRIPTION (provided by applicant): I am an Assistant Professor with the Center of Excellence for Eating Disorders in the Department of Psychiatry at The University of North Carolina (UNC). I have training in behavior genetics and eating disorders, with a focus on bulimia nervosa (BN) and related symptomatology. I am seeking training in "-omic sciences" (i.e., genomics, transcriptomics), advanced genetic epidemiological methods, anorexia nervosa- related psychopathology, and longitudinal data analysis. Career Goals: I want to bring eating disorder outcome research to the next level by merging my specific interest in genetics with my emerging interest in anorexia nervosa (AN) treatment outcome, specifically relapse. Thus, my core career goal is to develop an understanding of biomarkers (-omic markers, biological markers) of AN treatment outcome. I will use this knowledge to develop integrated profiles of relapse risk, which will inform novel, biologically-informed, and effective treatment interventions Career Development: I plan to build my skills and expertise in five areas: 1. AN psychopathology, treatment approaches, and outcome; 3. Definitions of recovery in the eating disorders field; 3. Advanced -omic sciences and genetic epidemiological methods 4. Longitudinal data analyses including latent trajectory modeling. 5. The responsible conduct of research. Research Project: The proposed project leverages existing resources by using two ongoing longitudinal parent projects at UNC to identify biomarkers of relapse after inpatient treatment for AN. Parent projects include: 1) Biomarkers of Anorexia Nervosa (BAN)-100 women admitted for inpatient treatment for AN assessed at admission and discharge, and then 3, 7, and 12 months post-discharge. Assessments include biomarkers (cortisol, adrenocorticotropic hormone, norepinephrine, and gene expression) as well as psychological, behavioral, and cognitive symptomatology; and 2) Road to Recovery in Eating Disorders (RRED), a subsample of BAN participants (n=60) followed-up 1 and 2-years post-discharge. The definition of relapse used in this proposal is operationalized as "weight change," or the amount of weight lost (or gained and maintained) since hospital discharge (follow-up weight minus discharge weight). First, I will examine gene expression change during therapeutic weight restoration using RNAseq. Second, I will examine the association between biomarkers (gene expression change and HPA-axis and adrenergic pathway activation) and psychological, behavioral, and cognitive factors and weight change at 3-time points within 1-year of discharge from treatment from a specialized eating disorder inpatient unit (BAN sample). These results will identify preliminary profiles of weight change. Third, using sophisticated longitudinal modeling strategies learned during the course of this award period, I will characterize the long-term pattern of weight maintenance/relapse from inpatient discharge to 2-years post-discharge in patients with AN (RRED sample). In future independent applications (R01s) these results will inform further exploration of the influence of -omic factors on treatment outcome-such as the development of a polygenic risk score and the impact of this score on relapse and provide biological targets for treatment and screening. Only through the understanding of biomarkers of theraputically restored weight loss in AN, can we fully identify those at risk for relapse in orderto develop effective treatment protocols-ultimately improving AN outcome. Environment: The research and training will take place in the Departments of Psychiatry and Genetics at UNC. Mentorship: The mentorship team includes lead mentor, Dr. Cynthia Bulik, a clinical psychologist, and internationally recognized expert in eating disorder research and whose funded interests range from genomics to treatment. Secondary mentors include: Dr. Patrick Sullivan, a psychiatrist and leading expert in "psychiatric -omics;" Dr. Kari North, a genetic epidemiologist who will provide expertise in longitudinal data analysis and methods and integrating genetic and nongenetic data into these analysis; Dr. Anna Bardone-Cone, a clinical psychologist and recognized expert in defining recovery in eating disorders; and Dr. Daniel Bauer, a quantitative psychologist and expert in longitudinal modeling.