PET IMAGING OF THE MU OPIOID RECEPTORS IN BULIMIA NERVOSA

神经性贪食症中 Mu 阿片受体的 PET 成像

• 批准号: 7378865
• 负责人: ANGELA S GUARDA
• 金额: $ 1.71万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7378865
• 关键词: PET; IMAGING; MU; OPIOID; RECEPTORS

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.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。背景和理由：神经性贪食症的原因尚不完全理解。这种节食障碍的特征是稀薄的驱动力高估了，该动力维持了限制，暴饮暴食和呕吐行为的循环。贪食症行为，尤其是偶尔的暴饮暴食和节食，在年轻女性中很常见，但是只有3％的女性人口发展为神经性贪食症的完整综合征。由于目前在西方文化中的理想和饮食动力较薄，因此与生物学性状相关的差异可能会使发展贪食症与试验贪食症行为的人区分开。动物和人类研究已将阿片类药物系统牵涉到喂养行为，我们假设阿片类体系中存在性状和与国家相关的差异，这是这种行为障碍固有的增强质量的基础。我们建议使用正电子发射断层扫描（PET）来测量治疗前后神经性神经性贪食症患者和对照妇女的MU阿片受体。该实验室的初步研究表明，鼠尾草女性左岛的MU阿片类药物结合降低，并且这种减少与报道的粗暴行为频率相关。与增强有关的其他大脑区域显示与这些行为有正相关。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，并通过治疗特别是饮食行为的标准化来检查MU受体的变化。 研究问题：这项研究的具体目的是：1）在神经性贪食症和匹配正常对照的女性患者中，PET测量PET区域脑MU阿片类药物受体。假设1a：PET成像证明了与正常对照组相比，神经性贪食症患者中MU阿片受体改变的区域。假设1B：区域MU阿片类受体的异常与异常饮食行为的定量度量相关。 2）在神经性贪食症患者的认知行为疗法（CBT）之前和之后，PET测量pET区域MU阿片受体的变化。假设2a：治疗后局部MU阿片受体的异常，并降低了粗暴行为的频率。假设2b：治疗后区域MU阿片受体的变化与临床反应有关CBT的反应。假设2c：治疗后区域MU阿片受体的变化与复发时间相关，并在治疗完成后恢复异常饮食行为。 设计：该研究项目将在3年内进行，并将调查：（1）乳液受试者以及年龄和体重匹配的对照中的脑阿片类受体结合的差异，以及（2）CBT和行为改变对神经性贪食症的脑阿片类药物的影响。贪食症的受试者在治疗开始时和CBT 10周后将进行PET扫描。对照受试者将在研究进入时进行扫描，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：受试者将包括20个健康对照和20名神经性贪食症的女性。要列入研究，参与者必须年满18至35岁，女性，体重正常（体重指数= 19-25），并符合DSM-IV神经性贪食症的DSM-IV标准，其主要清除方法是呕吐。那些符合任何其他轴I障碍标准，孕妇或接受药物治疗的参与者患有严重的疾病（包括艾滋病毒，癫痫发作疾病，中枢神经系统疾病）或对阿片类药片过敏。参与者每天必须抽烟不到一包香烟，筛查尿液毒理学阴性，并且每周喝不超过14种酒精饮料。 结果指标：结果措施包括异常和区域MU阿片类受体的变化，与饮食失调相关的认知和行为的变化（例如，敦促狂暴，呕吐频率），禁食实验室的变化以及相反的时间。