Project Summary In this application for a Stephen I. Katz Early Investigator Research Project Grant, the principal investigator, Dr. Amanda E. Lyall, proposes a project that will support a new research direction for her career: the transition from the use of neuroimaging to study psychotic disorders to the investigation of restrictive eating disorders. The over- arching goal of this application is to comprehensively characterize the impact of restrictive eating disorders on white matter development. This study will leverage unique access to extant neuroimaging, clinical, blood, and dietary intake data collected under 4 parent NIMH grant mechanisms (R01MH103402; R01MH108595; R01MH116205; K23MH125143) at the Eating Disorders Clinical Research Program at Massachusetts General Hospital, Harvard Medical School. We will use our well-validated diffusion magnetic resonance imaging (dMRI) harmonization framework to combine these data with 2 publicly available dMRI datasets of healthy controls: The Philadelphia Neurodevelopmental Cohort and The Human Connectome Project – Young Adult, yielding a cohort of harmonized imaging data spanning the period of white matter development from ages 9 to 40 years. With these data, we will examine the trajectories of global and region-specific white matter development using advanced dMRI analysis tools between healthy controls and individuals with restrictive eating disorders (Aim 1). Next, we will determine the extent to which age or pubertal stage modifies the relationship between potential white matter alterations in individuals with restrictive eating disorders and the duration of dietary restriction (Aim 2). Finally, we will evaluate the extent to which total caloric and/or specific nutritional deficiencies that arise because of severe dietary restriction impact white matter development (Aim 3). We believe that the information generated within this proposal will provide a critical first step in developing a knowledge base about the impact of severe dietary restriction on brain development. This proposal will provide an opportunity to identify vulnerable periods where therapeutic interventions may be necessary or have the most impact. Additionally, the results of this study may also provide a foundation for future work to test the effectiveness and tolerability of novel applications of non-invasive individualized therapies centering on improving white matter health.

Narrative Restrictive eating disorders are a debilitating and life-threatening group of psychiatric illness characterized by restricted dietary intake. At present, there are no studies investigating the potential neurobiological impacts dietary restriction may have on the developing brain, particularly white matter, which does not mature until the third decade of life. Using state-of-the-art image processing tools and already collected data, this proposal will generate important and currently unknown information about the interplay between brain development and severe dietary restriction, which may assist in the identification of critical developmental periods of increased vulnerability or optimal periods for clinical interventions.