Anorexia nervosa (AN) is a debilitating, often chronic, and sometimes fatal eating disorder (ED) that typically develops in adolescence. The etiology of AN is likely complex, yet remains unknown, and as a result, current treatments lack sufficient efficacy. Significant symptom heterogeneity exists, yet is not well captured by current diagnostic criteria. Thus, the identification of dimensional constructs underlying ED symptoms and their neural correlates is critical to improve our mechanistic understanding of ED and identify novel therapeutic targets to inform precision medicine. Behavioral symptoms of AN, such as food restriction (AN-R) and binge/purge episodes (AN-BP), arise from maladaptive decision-making. Decision-making is governed by two systems: 1) goal-directed learning reflects flexible and purposeful actions based on anticipated outcome, and 2) habit learning reflects automatic, efficient, and inflexible choices established by previous reinforcement. These learning systems are mediated by separate, yet overlapping, corticostriatal circuits and can be computationally modeled using a two-step sequential decision-making task. Difficulty arbitrating between these systems, resulting in an over-reliance on one strategy over the other, may contribute to divergent AN symptoms. This proposal tests the novel hypothesis that goal-directed and habit learning under conditions of reward and loss differs in AN and is uniquely associated with divergent symptoms and corticostriatal connectivity. Adolescent girls ages 14-17 with AN-R, AN-BP or who are healthy controls will undergo neuroimaging to assess resting state functional connectivity and microstructural integrity of corticostriatal networks, followed by performing the two-step learning task outside the scanner under conditions of reward and loss. For each participant, a weighting factor (?), representing the relative balance between goal-directed and habit learning, will be calculated for gain and loss conditions. After scanning, AN participants will complete a 14-day ecological momentary assessment protocol to evaluate naturalistic, momentary experiences of ED symptoms.
Aim 1 will determine the behavioral differences in goal-directed and habit learning under conditions of reward and punishment in individuals with AN- R, AN-BP and healthy controls.
Aim 2 will examine the association of goal-directed and habit learning for reward and punishment with symptoms and real-world experiences in AN to determine whether learning differences contribute to divergent symptoms.
Aim 3 will determine whether corticostriatal circuits associated with goal- directed and habit learning for reward and punishment differ by group and condition to inform neural mechanisms of altered reinforcement learning in AN. Data will support a future longitudinal R01 application to test a dimensional approach of behavioral phenotyping based on reinforcement learning in a wider spectrum of restricting and binge-type EDs to inform a neurodevelopmental model. Defining meaningful biomarkers in ED would be a major advance in the field, as it would allow the development of new treatment approaches to reduce poor outcome.

Public Health Relevance

Maladaptive decision-making and learning contribute to disordered eating in anorexia nervosa (AN). This study will determine how the balance of goal-directed and habit learning is shifted in adolescent AN, is influenced by reward and punishment outcome, and corresponds to divergent clinical symptoms and neural network connectivity. Advancing our understanding of dimensional constructs underlying behavioral symptoms in AN will improve etiological models, identify novel therapeutic targets, and advance innovative treatment development.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Exploratory/Developmental Grants (R21)
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Child Psychopathology and Developmental Disabilities Study Section (CPDD)
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Prabhakar, Janani
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University of California, San Diego
Schools of Medicine
La Jolla
United States
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