The developmental role of metabolism, appetite and growth in eating disorders: exploring novel longitudinal risk pathways

The Eating Disorders (full and partial syndrome anorexia nervosa and bulimia nervosa and binge eating disorder) are life-threatening illnesses that start in adolescence and affect between one and two in ten adolescents and young adults. There is a lack in our understanding of why eating disorders develop, which affects our ability to develop good treatments and adequately prevent eating disorders. This project builds on our preliminary data showing that metabolism and growth might play a role in the development of eating disorders; and aims to understand if metabolic function, appetite and growth factors precede onset of eating disorders. We also aim to explore whether these factors might be related to individuals' genetic make up, using novel methodologies and based on novel genetic findings. This study will be based on data from the Avon Study of Parents and Children (ALSPAC), and well-known and unique longitudinal study based in the UK. This study will be fundamental in providing us with an understanding of novel risk mechanisms for adolescent and young adult eating disorders that can be further investigated in larger and more detailed studies following this project.

This study builds on novel preliminary data [from prospective data and genetic studies], suggesting that metabolism and growth might have a yet unexplored role in the development of eating disorders. We will use data prospectively collected from the Avon longitudinal Study of Parents and Children (ALSPAC); a longitudinal birth cohort of ~13,000 children enrolled before birth and followed up to age 25. We will use data collected on metabolism, anthropometry and eating throughout childhood, and data on eating disorders we collected [at 3 timepoints in adolescence] and we are currently collecting at age 24. We will test our hypotheses that metabolic profiles, and eating patterns in childhood differentially predict full and sub-threshold eating disorders in adolescence and young adulthood using longitudinal regression models. We will then explore: 1. whether genetic risk scores for Anorexia Nervosa and high BMI are associated with distinct metabolic profiles in mid childhood, growth throughout childhood and childhood under-eating, AN and AN behaviours in adolescence and young adulthood; 2. whether a genetic risk score for high BMI is associated with distinct metabolic profiles in mid childhood, growth throughout childhood, childhood over-eating and loss of control eating, and binge eating and/or purging behaviours and disorders. This project will be foundational in: 1. being the first to study metabolic and appetitive risk factors for eating disorders prospectively, whilst also exploring their underlying genetic structure; 2. leading to new insights into the pathophysiology of eating disorders; 3. helping clarify risk pathways that can then be integrated into a risk model to be tested in larger and more detailed clinical, register-based and population-based studies.

This project aims to clarify the role of metabolic, appetitive, and growth risk factors on the development of eating disorders (ED) in adolescence and young adulthood drawing upon the fields of obesity and genetics. This study is based on a large, well-studied population-based sample (ALSPAC). We have applied novel discoveries to generate a new hypothesis on why eating disorders develop. Testing the role of metabolic, appetitive and growth factors longitudinally for the first time will allow impact on future research endeavours; building on this study for future risk hypothesis development and potential discovery of new pathophysiological pathways to be tested in animal, clinical and population-based research.

The project will have public health implications for the prevention of ED. Testing the hypothesized risk model will allow understanding and clarification of risk pathways for ED, allowing in the medium to long term more targeted early intervention, prevention, and detection of at risk individuals.
Clinical implications to patients and families: understanding metabolic, growth and appetitive pathways leading to ED, and their genetic underpinning will aid future the development of novel treatment targets for eating disorders (at present there are no pharmacological treatments for anorexia nervosa, and less than 50% of patients with ED recover from their illness, therefore developing new treatments is crucial).
Society and the public will benefit in the medium to long term from this study thanks to the new hypotheses being tested. Improved ability to develop treatment options and to prevent ED will in the long term improve well-being and decrease cost to the NHS for treatment of ED patients. Renewed understanding of the role of nature vs. nurture in risk of ED will help sufferers and families in lowering societal and individual stigma towards ED. We will ensure appropriate dissemination at public events, for example ICH has an annual dissemination event (Open day) for the lay public, as does Great Ormond Street Hospital (GOSH).
Stakeholders
Given the high quality data and generalizability of findings expected, the results of this study can have implications for policymakers on prevention of ED, and the need to apply a broader perspective to the study of prevention and early intervention of eating and weight disorders.
International impact
The international nature of the study team used will ensure broad uptake and further study of any results as well as providing a fast-track for dissemination of findings.

Training
Impact will ensue on the research teams and researchers at the relevant institutions involved in this project following capacity building and training, both in terms of specific research techniques and transferable skills. Examples of more specific teaching include: 1. MSc in Eating Disorders and Clinical Nutrition [Dr. Micali set this course up with a colleague at UCL in 2013, and she co-lead it between 2013 and 2015] the MSc currently includes about 25 students from all over the world. Dr Micali regularly teaches on this course and supervises several research dissertation projects; 2. trainees in child and adolescent psychiatry that Dr. Micali regularly supervises and teaches at GOSH and UCL; 3. PhD and MSc students at UCL, LSHTM and University of Bristol.