This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Background and Rationale:The cause of bulimia nervosa is incompletely understood. This dieting disorder is characterized by an overvalued drive for thinness, which sustains a cycle of restricting, binge eating and vomiting behaviors. Bulimic behaviors, especially occasional binge eating and dieting, are common in young women, however only 3% of the female population develop the full syndrome of bulimia nervosa . Since the thin ideal and the drive to diet are currently normative in western culture, biological trait-related differences likely distinguish individuals who develop bulimia from those who experiment with bulimic behaviors. Animal and human studies have implicated the opioid system in feeding behavior and we hypothesize that there are both trait and state-related differences in the opioidergic system that underlie the reinforcing qualities inherent in this behavioral disorder. We propose to use positron emission tomography (PET) to measure mu opioid receptors in patients with bulimia nervosa before and after treatment and in control women. Preliminary studies from this laboratory have shown that there is a decrease in mu opioid binding in the left insula of bulimic women and that this decrease is correlated with reported frequencies of bulimic behaviors. Additional brain regions related to reinforcement show a positive correlation with these behaviors. These data suggest a relationship between opioid receptors and the etiology or symptoms of bulimia. We propose to elucidate this relationship and to examine the change in mu receptors with treatment, specifically with normalization of eating behavior.Study Questions:
The specific aims of this study are:1) Measure regional brain mu opioid receptors by PET in female patients with bulimia nervosa and matched normal controls.Hypothesis 1A: PET imaging demonstrates regions of altered mu opioid receptors in bulimia nervosa patients compared with normal control subjects.Hypothesis 1B: Abnormalities in regional mu opioid receptors are correlated with quantitative measures of abnormal eating behaviors.2) Measure the change in regional mu opioid receptors by PET before and after cognitive behavioral therapy (CBT) in patients with bulimia nervosa.Hypothesis 2A: Abnormalities in regional mu opioid receptors normalize following treatment and reduction in the frequency of bulimic behaviors.Hypothesis 2B: Changes in regional mu opioid receptors following treatment correlate with the clinical response to CBT.Hypothesis 2C: Changes in regional mu opioid receptors following treatment correlate with time to relapse and the resumption of abnormal eating behavior following completion of treatment.Design:This research project will be conducted over 3 years and will investigate: (1) differences in brain opioid receptor binding in bulimic subjects and in age and weight-matched controls and (2) the effect of CBT and behavioral change on the brain opioid system in bulimia nervosa. Subjects with bulimia will have a PET scan at the beginning of therapy and after 10 weeks of CBT. Control subjects will have a scan at study entry and a repeat scan 10 weeks later to assess reproducibility of the measurement.Study Population:Subjects will include 20 healthy controls and 20 women with bulimia nervosa. To be included in the study, participants must be 18 to 35 years of age, female, of normal weight (body mass index = 19-25), and meet DSM-IV criteria for bulimia nervosa-purging type, with the primary method of purging being vomiting. Those participants who meet criteria for any other Axis I disorder, are pregnant or undergoing pharmacotherapy, have a serious medical condition (including HIV, seizure disorder, CNS disease) or are allergic to opiates will be excluded. Participants must smoke less than one pack of cigarettes per day, screen negative for a urine toxicology, and drink no more than 14 alcoholic beverages per week. Outcome Measures:Outcome measures include abnormalities and changes in regional mu opioid receptors, changes in cognitions and behaviors associated with eating disorders (e.g., urges to binge, vomiting frequency), changes in fasting labs, and time to relapse.
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