Individuals with anorexia nervosa (AN) and bulimia nervosa (BN) have aberrant feeding behavior, and disturbances of emotionality and impulse control. Imaging studies from our last funding period suggest that these symptoms are related to dysfunction of limbic and cognitive circuits. This application will use blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to examine neural substrates underlying appetitive, reward, and cognitive dysregulation in AN and BN. Over 5 years we will study 50 women recovered (REC) from AN and 50 female REC BN (to avoid the confounding effects of malnutrition and because considerable data suggests these symptoms are traits that persist after recovery) compared to 50 healthy control women (CW), all of whom are 18 to 45 years old.
AIM 1 : The anterior insula (AI) and related regions integrate sensory/hedonic aspects of taste and interoceptive awareness in the service of homeostasis. We will use a sucrose gustatory challenge and will provoke homeostasis by comparing a hungry state to a satiated state. Our data suggest that restricted eating and weight loss occurs in AN because feeding elicits diminished insula homeostatic response to hunger, whereas overeating in BN is related to exaggerated hunger signal.
AIM 2 : Several lines of evidence suggest that disturbed striatal function in AN contributes to anhedonia and over concern with future consequences. Using a delayed discounting task, we expect that REC AN will show a preference for later rewards compared to CW, reflecting aberrant anterior ventral striatum-limbic function, as well as overactive cognitive pathways, related to planning and assessment of consequences.
AIM 3 : Those with anorexia are rigid, inflexible, and behaviorally inhibited whereas BN have these traits as well as impulsivity and affective instability. We will use a validated motor inhibition task to characterize the neural substrates of inhibitory control. Preliminary data suggests REC AN show demand-specific alterations within a fronto-subthalamic circuit that is critically involved in motor inhibition and cognitive control. Taken together, these aims will enable us to better characterize cognitive and limbic dysfunction in these populations. Understanding biologic vulnerabilities in AN and BN is critical for developing effective treatment interventions for these often chronic and deadly disorders. This if the first resubmission of competing renewal MH042984

Public Health Relevance

There is considerable evidence that alterations in brain function contribute to disturbances of appetite, emotionality, and impulse control in anorexia and bulimia nervosa. This application will use functional magnetic brain imaging to characterize neuronal circuits and their relationship to behavior. Understanding the pathophysiology of eating disorders is necessary in order to devise new and more effective treatment interventions 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 #
5R01MH042984-18
Application #
7844846
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Meinecke, Douglas L
Project Start
1988-09-30
Project End
2014-03-31
Budget Start
2010-04-01
Budget End
2011-03-31
Support Year
18
Fiscal Year
2010
Total Cost
$572,467
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
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Bailer, Ursula F; Price, Julie C; Meltzer, Carolyn C et al. (2017) Dopaminergic activity and altered reward modulation in anorexia nervosa-insight from multimodal imaging. Int J Eat Disord 50:593-596
Wierenga, Christina E; Bischoff-Grethe, Amanda; Rasmusson, Grace et al. (2017) Aberrant Cerebral Blood Flow in Response to Hunger and Satiety in Women Remitted from Anorexia Nervosa. Front Nutr 4:32
Ely, Alice V; Wierenga, Christina E; Bischoff-Grethe, Amanda et al. (2017) Response in taste circuitry is not modulated by hunger and satiety in women remitted from bulimia nervosa. J Abnorm Psychol 126:519-530
Boutelle, K N; Wierenga, C E; Bischoff-Grethe, A et al. (2015) Increased brain response to appetitive tastes in the insula and amygdala in obese compared with healthy weight children when sated. Int J Obes (Lond) 39:620-8
Wagner, Angela; Simmons, Alan N; Oberndorfer, Tyson A et al. (2015) Altered sensitization patterns to sweet food stimuli in patients recovered from anorexia and bulimia nervosa. Psychiatry Res 234:305-13
Compan, Valérie; Walsh, B Timothy; Kaye, Walter et al. (2015) How Does the Brain Implement Adaptive Decision Making to Eat? J Neurosci 35:13868-78
Wierenga, Christina E; Bischoff-Grethe, Amanda; Melrose, A James et al. (2015) Hunger does not motivate reward in women remitted from anorexia nervosa. Biol Psychiatry 77:642-52
Wierenga, Christina E; Ely, Alice; Bischoff-Grethe, Amanda et al. (2014) Are Extremes of Consumption in Eating Disorders Related to an Altered Balance between Reward and Inhibition? Front Behav Neurosci 8:410
Grant, Igor; Franklin Jr, Donald R; Deutsch, Reena et al. (2014) Asymptomatic HIV-associated neurocognitive impairment increases risk for symptomatic decline. Neurology 82:2055-62

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