Common to all eating disorders (ED) are alterations in the motivation to eat , ranging from extreme food restriction and weight loss, to binge eating coupled with compensatory strategies like self-induced vomiting. Despite the traditional emphasis on these physical symptoms, they often overlap, and, along with significant diagnostic crossover (e.g., from anorexia nervosa to bulimia nervosa) over the course of one's illness, suggest shared features that are not well captured by current diagnostic criteria. This novel proposal aims to examine how RDoC-based temperament measures ? behavioral activation/impulsivity, behavioral inhibition, and effortful control ? identify clinically meaningful groups of adolescent ED patients that may reflect core dimensions of ED better than DSM diagnosis and correspond more strongly to brain function and clinical symptoms. These temperaments are thought to play a role in ED behavior because they are linked to altered incentive processing, particularly in the ventral striatum and insula, which guides approach and avoidance motivation via evaluation of anticipated and actual outcomes. For example, in other approach disorders, like addiction, high impulsivity is associated with reduced striatal activity during monetary reward anticipation,8 whereas in avoidance disorders, anxiety and inhibition are linked with an increased insula response to reward anticipation,9 and decreased striatal outcome response.10 We test the novel hypothesis that over- and under- controlled eating behavior reflects aberrant incentive processing stemming from altered evaluation of anticipated and/or actual outcome to induce compensatory consumption (approach) or avoidance behaviors. We will recruit 150 females currently ill with an ED and 50 controls ages 14-17 to investigate how temperaments reflecting greater inhibition, impulsivity, or effortful control correspond to 1) clinical symptoms and 2) the brain's response to anticipation and outcome of appetitive and aversive generalized (monetary wins and losses) and disorder-specific (taste) salient stimuli, and 3) by collecting follow-up clinical data one year later, identify how temperament-based subtypes predict ED symptom change (e.g., clinical prediction). Demonstrating that certain temperament and personality characteristics are directly related to brain response to both money and taste, rather than only disorder-specific food stimuli, and that correspond to clinical symptoms, will provide greater support for the contribution of biological processes underlying incentive processing to ED behavior. We will also explore whether temperament is meaningfully related to white matter structural connectivity and resting state functional connectivity to further characterize brain-behavior relationships in adolescent ED. Resolving these questions is critical to our mechanistic understanding of the neural basis of disordered eating and will move us towards more meaningful characterization and development of more targeted intervention and prevention strategies than subtyping by physical symptoms.

Public Health Relevance

The proposed study of adolescent eating disorders (ED) will examine the association of temperament-based research domain criteria (RDoC)-derived endophenotypic classifications, brain activation during incentive processing, and ED symptoms at time of scan and one year later. Revealing how the neural correlates of approach and avoidance motivation are altered in ED will increase understanding of transdiagnostic biological and cognitive processes underlying ED psychopathology. A better understanding of these temperament constructs underlying behavior and neurobiology is critical for developing targeted, more powerful therapies for these often chronic and deadly disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH113588-04
Application #
9978940
Study Section
Child Psychopathology and Developmental Disabilities Study Section (CPDD)
Program Officer
Prabhakar, Janani
Project Start
2017-07-21
Project End
2022-06-30
Budget Start
2020-07-01
Budget End
2021-06-30
Support Year
4
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of California, San Diego
Department
Psychiatry
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Bischoff-Grethe, Amanda; Wierenga, Christina E; Berner, Laura A et al. (2018) Neural hypersensitivity to pleasant touch in women remitted from anorexia nervosa. Transl Psychiatry 8:161
Wierenga, Christina E; Lavender, Jason M; Hays, Chelsea C (2018) The potential of calibrated fMRI in the understanding of stress in eating disorders. Neurobiol Stress 9:64-73