PET IMAGING OF THE MU OPIOID RECEPTORS IN BULIMIA NERVOSA

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 背景和理由： 神经性暴食症的原因尚不完全清楚。这种节食障碍的特征是一种被高估的瘦身动力，这种动力维持着限制、暴饮暴食和呕吐行为的循环。暴食行为，特别是偶尔暴饮暴食和节食，在年轻女性中很常见，但只有3%的女性会患上神经性暴食症的全部综合症。由于瘦的理想和节食的驱动力目前在西方文化中是标准的，与生物特征相关的差异可能会将患上暴食症的人与那些尝试暴食行为的人区分开来。动物和人类的研究表明，阿片系统与摄食行为有关，我们假设阿片能系统存在与特征和状态相关的差异，这些差异是这种行为障碍固有的强化特征的基础。我们建议使用正电子发射断层扫描(PET)来检测神经性贪食症患者治疗前后和对照组妇女的Mu阿片受体。该实验室的初步研究表明，暴食症女性左侧脑岛的u阿片结合量减少，而且这种减少与暴食症行为的报告频率有关。与强化相关的额外大脑区域与这些行为呈正相关。这些数据表明阿片受体与暴食症的病因或症状之间存在关系。我们建议阐明这种关系，并通过治疗，特别是饮食行为的正常化来检查Mu受体的变化。 研究问题： 这项研究的具体目的是： 1)用正电子发射计算机断层扫描(PET)测定女性神经性贪食症患者和正常对照组的脑局部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变化。 假设1B：区域MU阿片受体的异常与异常进食行为的量化指标相关。 2)用正电子发射计算机断层扫描(PET)检测神经性贪食症患者认知行为治疗(CBT)前后局部MU阿片受体的变化。 假设2A：局部阿片受体异常在治疗和减少暴食行为的频率后恢复正常。 假设2B：治疗后局部MU阿片受体的变化与CBT的临床反应相关。 假设2C：治疗后局部MU阿片受体的变化与复发时间和治疗结束后异常进食行为的恢复有关。 设计： 本研究为期3年，将研究：(1)暴食症受试者和年龄、体重匹配的对照组之间脑阿片受体结合的差异；(2)CBT和行为改变对神经性暴食症患者脑阿片系统的影响。暴食症患者将在治疗开始时和CBT治疗10周后进行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，以评估测量的重复性。 研究人群： 研究对象包括20名健康对照和20名患有神经性暴食症的女性。要纳入这项研究，参与者必须是18至35岁的女性，正常体重(体重指数=19-25)，并符合DSM-IV关于神经性贪食症清除类型的标准，主要清除方法是呕吐。那些符合任何其他Axis I障碍的标准、怀孕或正在接受药物治疗、有严重疾病(包括艾滋病毒、癫痫障碍、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不到一包，尿毒学筛查阴性，每周饮酒不超过14杯。 结果衡量标准： 结果指标包括区域MU阿片受体的异常和变化、与进食障碍相关的认知和行为的变化(例如，暴饮暴食、呕吐频率)、禁食实验室的变化以及复发时间。

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.