PET IMAGING OF THE MU OPIOID RECEPTORS IN BULIMIA NERVOSA

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。背景和理由：神经性贪食症的病因尚不完全清楚。这种饮食失调的特点是对苗条的过度追求，这种追求维持了一个限制、暴饮暴食和呕吐行为的循环。暴食症的行为，尤其是偶尔的暴饮暴食和节食，在年轻女性中很常见，然而只有3%的女性人口发展为神经性贪食症的完全综合征。由于瘦的理想和节食的驱动力目前在西方文化中是规范的，生物性状相关的差异可能区分了患暴食症的个体和那些尝试暴食行为的个体。动物和人类的研究表明阿片系统与摄食行为有关，我们假设阿片系统中存在特征和状态相关的差异，这些差异是这种行为障碍中固有的强化品质的基础。我们建议使用正电子发射断层扫描（PET）来测量神经性贪食症患者治疗前后和对照组女性的mu阿片受体。本实验室的初步研究表明，暴食症女性左脑岛的mu -阿片结合减少，并且这种减少与暴食行为的报道频率相关。大脑中与强化相关的其他区域与这些行为呈正相关。这些数据表明阿片受体与贪食症的病因或症状之间存在关系。我们建议阐明这种关系，并检查治疗后mu受体的变化，特别是饮食行为的正常化。研究问题：本研究的具体目的是：1)通过PET检测女性神经性贪食症患者和匹配的正常对照者的脑区域mu阿片受体。假设1A：与正常对照组相比，PET成像显示神经性贪食症患者的mu阿片受体区域发生了改变。假设1B：区域mu阿片受体的异常与异常饮食行为的定量测量相关。2)应用PET检测神经性贪食症患者认知行为治疗（CBT）前后区域mu阿片受体的变化。假设2A：局部mu阿片受体的异常在治疗后恢复正常，暴食行为的频率减少。假设2B：治疗后区域mu阿片受体的变化与CBT的临床反应相关。假设2C：治疗后区域mu阿片受体的变化与治疗结束后复发的时间和异常饮食行为的恢复有关。设计：本研究项目将进行为期3年的研究，主要研究：(1)贪食症受试者与年龄和体重匹配对照组脑阿片受体结合的差异；(2)CBT和行为改变对神经性贪食症脑阿片系统的影响。暴食症患者将在治疗开始和CBT治疗10周后接受PET扫描。对照受试者将在研究开始时进行扫描，并在10周后进行重复扫描，以评估测量的可重复性。研究人群：受试者包括20名健康对照者和20名患有神经性贪食症的女性。纳入研究的参与者必须为18 - 35岁，女性，体重正常（体重指数= 19-25），符合DSM-IV神经性贪食泻型标准，主要泻型为呕吐。符合任何其他轴I障碍标准的参与者，怀孕或正在接受药物治疗，患有严重疾病（包括艾滋病毒，癫痫发作，中枢神经系统疾病）或对阿片类药物过敏的参与者将被排除在外。参与者必须每天吸烟少于一包香烟，尿液毒理学检测呈阴性，每周饮酒不超过14杯。结果测量：结果测量包括区域mu阿片受体的异常和改变，与饮食失调相关的认知和行为的改变（例如，暴食的冲动，呕吐频率），禁食实验室的变化和复发时间。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for 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.