Anorexia nervosa (AN) is among the most pernicious of psychiatric disorders, demonstrating elevated rates of mortality, and a chronic and relapsing illness course that is refractory to current treatment approaches. Further, the etiology of AN remain elusive. While more efficacious treatments are urgently needed, the development of precision treatments is dependent upon the identification of mechanistic pathways that underpin symptom presentations. This mentored patient-oriented research career development award (K23) will provide targeted training and mentorship for Dr. Stuart Murray to embark upon a career of independent research oriented towards the delineation of key mechanistic pathways underpinning AN symptomatology. This, in turn, will allow subsequent treatment development efforts to be targeted towards precise pathogenic mechanisms to alter the pathway by which they drive AN symptomatology. The projects outlined in this proposal relate specifically to fear conditioning and fear extinction, given (i) the centrality of fear in presentations of AN, (ii) the substantial overlap between AN and disorders characterized by perturbations in fear conditioning, and (iii) and the absence of empirical evidence relating to fear acquisition and fear extinction in AN. With a team of expert mentors and consultants that collectively bridge the fields of AN, translational psychiatry, neuroimaging, fear extinction, and biostatistics, Dr. Murray aims to (i) index psychological and physiological markers of fear acquisition and fear extinction during a fear conditioning paradigm utilizing both neutral cues, and disorder-specific cues, and (ii) map the neural biomarkers of both fear acquisition and fear extinction via neuroimaging. It is expected that the results of this study will contribute significantly to the development of precision targets for AN treatments, and the training encapsulated herein will position Dr. Murray as an independent researcher in the field of precision treatment for AN.
Anorexia nervosa (AN) is a profoundly dangerous and treatment-resistant psychiatric illness of unknown etiology, which centrally involves a fear of food consumption. This study is novel in utilizing self-report, physiological and neuroimaging data to index pathways of fear conditioning and fear extinction in AN, to both neutral- and food-related conditioned cues. A mechanistic understanding of the processes of fear conditioning and extinction in AN will assist in the delineation of precise treatment targets.
