About This Research Project
Timothy H. Moran, Ph.D.
Paul R. McHugh Professor
Executive Vice Chair
Department of Psychiatry and Behavioral Sciences
Johns Hopkins University School of Medicine
Scientific Goal & Project Description
Weight restoration is necessary but not sufficient for recovery from Anorexia Nervosa (AN) and relapse rates following successful inpatient treatment and nutritional rehabilitation remain significant. The goal of this project is to examine oxidative stress as a potential biological mechanism underlying propensity towards relapse in patients with Anorexia Nervosa. Acutely ill patients with Anorexia Nervosa have been shown to have increased oxidative stress, an imbalance between antioxidants and free-radicals compared to healthy controls. A low ratio of antioxidants to free radicals has been observed in several disease states including obsessive-compulsive disorder and drug addiction, other psychiatric disorders characterized by compulsive behaviors and high rates of relapse. This project will address the following outstanding questions:
- Does the oxidative state of patients with Anorexia Nervosa improve with weight regain?
- Is there a relationship between initial oxidative state prior to treatment and either rate of weight gain in treatment, or rate of relapse at 1-year post-treatment?
- Can administration of N-acetylcysteine to individuals with AN curb compulsive exercise and restrictive eating behavior and minimize the risk of relapse to these behaviors following hospital-based weight restoration treatment.
Researchers will test blood from patients at admission and at discharge from the Johns Hopkins Eating Disorder Program, a highly successful inpatient weight restoration program for patients with Anorexia Nervosa directed by Dr. Angela Guarda. Blood samples will be processed by High-Performance Liquid Chromatography (HPLC) for markers of oxidative stress including cysteine and glutathione. These values will be compared to those from healthy controls to replicate published findings demonstrating deficits in the oxidative state in patients with AN. Following weight restoration, patients will be administered an antioxidant, N-acetylcysteine, to determine if this provides therapeutic relief and prevents relapse.
Patients with Anorexia Nervosa enrolled in the Johns Hopkins Inpatient Eating Disorder Program.
Drs. Moran, Guarda, and Hurley are seeking funding to:
• Purchase equipment and supplies needed for high-performance liquid chromatography of systemic oxidative state in patients with Anorexia Nervosa, and in matched healthy controls.
• Support a pilot study for weight restored patients with Anorexia Nervosa, to determine whether administration of the antioxidant and nutritional supplement N-acetylcysteine curbs compulsive behaviors including restrictive eating and exercise following weight restoration and impacts relapse risk.
Researchers involved in these projects:
Angela Guarda, MD is the Stephen and Jean Robinson Associate Professor of Eating Disorders in the Department of Psychiatry and Behavioral Sciences at the Johns Hopkins School of Medicine. She has over 20 years’ experience as the Director of the Eating Disorders Program at Johns Hopkins Hospital and is an expert is in the intensive treatment of adult anorexia nervosa with high severity and chronicity. Her clinical research interests include improving behavioral interventions and weight restoration outcomes for severe anorexia nervosa. Her research lab is interested in alterations in attention to food stimuli, decision-making around food choice and neurobiological alterations that contribute to sustaining dietary restriction and other weight control behaviors in persons with anorexia nervosa. Dr. Guarda has been the recipient of grant funding from both the National Institutes of Mental Health and the Klarman Family Foundation. She collaborates closely with Dr. Timothy Moran’s lab on translational research including meal-based studies examining disturbances in neuroendocrine hunger and satiety signaling that may sustain disordered eating behavior, and in the study of animal models of anorexia nervosa. Dr. Guarda is a member of the Miller Coulson Academy of Clinical Excellence, the Eating Disorders Research Society and the Academy of Eating Disorders and member of the editorial board of the International Journal of Eating Disorders.
Timothy H. Moran, Ph.D. is the Paul R. McHugh Professor of Motivated Behaviors in the Department of Psychiatry and Behavioral Sciences at the Johns Hopkins University School of Medicine. His overall research program is aimed at understanding the neural signaling pathways controlling food intake and body weight and the causes and consequences of obesity and eating disorders. His work has focused on brain/gut peptides as feedback controls of meal size and how these interact with hypothalamic and reward systems involved in overall energy balance. He has also examined the effects of exercise on food intake and hypothalamic signaling and how gestational and early developmental factors can bias metabolic programming through epigenetic mechanisms to contribute to obesity and type II diabetes. His lab conducts experiments at multiple levels using cell and rodent models and normal and patient populations. He collaborates widely on human studies involving obesity and eating disorders and on studies modeling aspects of the food environment and their effects of obesity.
Kimberly R. Smith, Ph.D. is a postdoctoral fellow in the Department of Psychiatry and Behavioral Sciences at the Johns Hopkins University School of Medicine. Her overall research interests lie in understanding the neurobiological mechanisms underlying eating pathologies with a particular focus on taste-driven behaviors. Her postdoctoral fellowship in clinical research, under the mentorship of Dr. Tim Moran and in collaboration with Dr. Angela Guarda, combines her doctoral work using rigorous psychophysical methods to understand the mechanisms of taste function with sophisticated neuroimaging techniques to effectively link structural and functional neural phenotypes that give rise to a complex range of feeding behaviors expressed in patients with obesity and eating disorders. Dr. Smith has received partial funding to support this project from the Hilda and Preston Davis Foundation.
Matthew M. Hurley Ph.D. Matt Hurley earned his Ph.D. in Biological Sciences from Marquette University in 2018 and is completing postdoctoral fellowship training under Dr. Moran on projects involving preclinical modeling of psychiatric disorders, including Anorexia Nervosa. His work includes primary responsibility for this project will be data analysis and interpretation of the molecular experiment. He will assist in coordinating the human subjects portion of this grant in terms of recruiting patients with AN as well as healthy controls. Additionally, he will help with any IRB approval requests as well as in giving presentations and preparing manuscripts.
Be Part Of The Solution
Timothy H. Moran, Ph.D.
Timothy H. Moran, Ph.D. is the Paul R. McHugh Professor of Motivated Behaviors in the Department of Psychiatry and Behavioral Sciences at the Johns Ho...Read More...