Anorexia nervosa (AN) is a devastating psychiatric illness with significant morbidity and mortality rates, and
relapse rates ranging from 40-80% after acute treatment. Extreme restriction of food intake is the central
behavioral disturbance in illness, and confers significantly greater risk for relapse. Illness follows a
heterogeneous course and clinical predictors of response to treatment are largely unknown. Maladaptive
behavior in AN has behavioral and neural features suggesting habitual control. Yet, brain-based factors that
relate to long-term outcomes and treatment response have not been studied. In other areas of psychiatry, both
neural predictors of persistent illness and neural predictors of treatment response have been identified through
patterns of neural activity and neural connectivity. By studying neural predictors of outcome in AN, this study
addresses a critical gap in knowledge about the treatment of AN.
This developmental study will leverage an existing clinical trial providing relapse prevention treatment for AN
for individuals with AN who normalized weight as inpatients in our treatment program. The intervention,
Relapse Prevention and Changing Habits (REACH+), targets habitual control of maladaptive behavior,
especially restriction of food intake. REACH+ compares different versions of cognitive and behavioral
psychotherapeutic interventions in a randomized design.
The proposed R21 will acquire fMRI data from patients hospitalized for AN who have achieved full weight
restoration, prior to starting REACH+ treatment. To identify neural predictors of outcome, we will acquire fMRI
activity during a task with established utility in capturing the maladaptive restriction that predicts relapse in AN
(Food Choice Task) as well as functional connectivity at rest. We will test whether these neural markers predict
weight slope after hospital discharge, an established marker of longer-term outcome, to test for biomarkers of
relapse. In addition, we will acquire fMRI activity during a cognitive control task with established utility in
predicting response to cognitive behavior therapy (in non-AN populations). We will explore whether individual
differences in cognitive control-related activity, as well as other patterns of resting state connectivity, moderate
response to variations in behavioral and cognitive interventions included in REACH+. By evaluating how neural
activity predicts outcome, this work is responsive to the NIMH call for the development of clinically relevant
biomarkers of recovery and relapse in AN. This study will establish new avenues for research in personalized
medicine in AN.