PET IMAGING OF THE MU OPIOID RECEPTORS IN BULIMIA NERVOSA

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 背景和依据： 神经性贪食症的原因是不完全了解。这种饮食失调的特征是对苗条的过度追求，这维持了一个限制、暴饮暴食和呕吐行为的循环。暴食行为，特别是偶尔的暴饮暴食和节食，在年轻女性中很常见，但只有3%的女性人口发展为神经性贪食综合征。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，生物特征相关的差异可能会区分患有暴食症的个体和那些实验暴食症行为的个体。动物和人类的研究表明，阿片类药物系统在喂养行为，我们假设，有两个特质和状态相关的差异，在阿片类药物系统的基础上，在这种行为障碍的固有的强化品质。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妇女的μ阿片受体。该实验室的初步研究表明，在暴食症女性的左丘脑中，μ阿片类药物结合减少，并且这种减少与报告的暴食症行为频率相关。与强化相关的其他大脑区域与这些行为呈正相关。这些数据表明阿片受体和贪食症的病因或症状之间的关系。我们建议阐明这种关系，并检查μ受体与治疗的变化，特别是饮食行为的正常化。 研究问题： 这项研究的具体目标是： 1)PET检测女性神经性贪食症患者和正常对照者脑内μ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μ阿片受体区域发生了改变。 假设1B：区域μ阿片受体的抑制与异常饮食行为的定量测量相关。 2)PET检测神经性贪食症患者认知行为治疗前后局部μ阿片受体的变化 假设2A：区域μ阿片受体的抑制在治疗后恢复正常，暴食行为的频率降低。 假设2B：治疗后局部μ阿片受体的变化与CBT的临床反应相关。 假设2C：治疗后局部μ阿片受体的变化与复发时间和治疗完成后异常饮食行为的恢复相关。 设计图： 本研究项目将进行3年以上，并将调查：（1）贪食症受试者与年龄和体重匹配的对照组脑阿片受体结合的差异，以及（2）CBT和行为变化对神经性贪食症脑阿片系统的影响。患有贪食症的受试者将在治疗开始时和10周CBT后进行PET扫描。对照受试者将在进入研究时进行扫描，并在10周后重复扫描，以评估测量的重现性。 研究人群： 受试者将包括20名健康对照和20名患有神经性贪食症的女性。 要纳入研究，参与者必须是18至35岁的女性，体重正常（体重指数= 19-25），并符合DSM-IV神经性贪食症-清除类型的标准，主要的清除方法是呕吐。 符合任何其他轴I疾病标准、妊娠或正在接受药物治疗、患有严重疾病（包括HIV、癫痫发作、CNS疾病）或对阿片类药物过敏的受试者将被排除。 参与者必须每天吸烟少于一包，尿液毒理学筛查阴性，每周饮酒不超过14杯。 结局指标： 结果指标包括局部μ阿片受体的异常和变化、与饮食失调相关的认知和行为的变化（例如，暴饮暴食的冲动，呕吐频率），空腹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.