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 #
5R01MH042984-21
Application #
8447059
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
2013-04-01
Budget End
2014-03-31
Support Year
21
Fiscal Year
2013
Total Cost
$538,579
Indirect Cost
$189,984
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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Filoteo, J Vincent; Paul, Erick J; Ashby, F Gregory et al. (2014) Simulating category learning and set shifting deficits in patients weight-restored from anorexia nervosa. Neuropsychology 28:741-51
Wierenga, Christina; Bischoff-Grethe, Amanda; Melrose, A James et al. (2014) Altered BOLD response during inhibitory and error processing in adolescents with anorexia nervosa. PLoS One 9:e92017
Radeloff, Daniel; Willmann, Kathrin; Otto, Lisa et al. (2014) High-fat taste challenge reveals altered striatal response in women recovered from bulimia nervosa: A pilot study. World J Biol Psychiatry 15:307-16
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
Kaye, Walter H; Wierenga, Christina E; Bailer, Ursula F et al. (2013) Nothing tastes as good as skinny feels: the neurobiology of anorexia nervosa. Trends Neurosci 36:110-20
Yau, Wai-Ying Wendy; Bischoff-Grethe, Amanda; Theilmann, Rebecca J et al. (2013) Alterations in white matter microstructure in women recovered from anorexia nervosa. Int J Eat Disord 46:701-8
Klabunde, Megan; Acheson, Dean T; Boutelle, Kerri N et al. (2013) Interoceptive sensitivity deficits in women recovered from bulimia nervosa. Eat Behav 14:488-92
Kaye, Walter H; Wierenga, Christina E; Bailer, Ursula F et al. (2013) Does a shared neurobiology for foods and drugs of abuse contribute to extremes of food ingestion in anorexia and bulimia nervosa? Biol Psychiatry 73:836-42
Oberndorfer, Tyson; Simmons, Alan; McCurdy, Danyale et al. (2013) Greater anterior insula activation during anticipation of food images in women recovered from anorexia nervosa versus controls. Psychiatry Res 214:132-41

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