No Way Around But Through: Mechanisms of Persistence and Remission of Habits in Anorexia Nervosa

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Anorexia nervosa (AN) is a serious disorder with a mortality rate among the highest of any psychiatric illness. Central to the morbidity and mortality of AN is a persistent tendency to restrict caloric intake below the body's needs, with a specific tendency to limit calories derived from fat. This perplexing behavior is highly resistant to change, even with a full course of inpatient treatment and weight restoration. Furthermore, restrictive eating patterns are linked to the high rates of relapse after hospital discharge. In order to improve outcomes and long-term remission rates, it is critical to better understand the pathophysiology of illness. This proposal specifically aims to elucidate mechanisms that contribute to the perpetuation of illness and, conversely, to sustained remission. One putative mechanism of persistent maladaptive behavior is habit formation, through which learned behaviors become relatively insensitive to goals. Habit behavior is associated with neural activity in dorsal frontostriatal systems. Here, we will assess habitual and goal-directed behavior across three experiments to provide an in-depth assessment of the behavioral and neural mechanisms that support persistence of illness, as well as remission from illness. This comprehensive battery includes an augmented Two-Step decision task to assess the preponderance of habitual vs goal-directed behavior (modified to improve habit sensitivity), the Avoidance Habit task to assess habit formation in the setting of aversive outcomes, and a Pavlovian Instrumental Transfer task to assess how strongly context cues exacerbate habitual behavior. The task battery will also measure general vs food-specific abnormalities. Our central hypothesis is that habits contribute to the persistence of illness, whereas goal-directed behavior contributes to remission. To examine brain and behavior characteristics associated with short and long-term remission, we leverage our longstanding research unit, which has a successful program for full weight restoration (acute remission), and has a Research Registry that has been in place for more than a decade. We will administer our task battery with fMRI to acutely weight restored inpatients with AN (n=80), individuals in longer-term remission from AN (n=40, recruited from the Research Registry), and healthy comparison women (HC, n=40). We will also invite all eligible patients in the Research Registry (n=397, currently) to complete our task battery online, in order to assess habitual vs goal-directed behavior across a large sample, spanning a range of experiences from relapse to long-term remission after acute weight restoration. In addition, the acutely weight restored AN sample will be followed for 6 months after hospital discharge, a time of high relapse risk, to examine longitudinally the association between behavioral and neural characteristics and outcome. Findings from this study will help determine whether the mechanisms that support persistence of illness also support remission, thereby clarifying targets for relapse prevention treatment.