PET IMAGING AND SEROTONIN LIGANDS IN EATING DISORDERS

描述：一些间接证据表明，大脑中的血清素 在患有神经性厌食症（AN）和神经性贪食症（BN）的女性中， 当他们生病和康复后。从理论上讲， 5-HT神经传递可能导致脆弱性（限制进食， 对秩序和完美主义的痴迷，避免伤害和负面影响） 这有助于发展AN和BN。反过来，营养不良可能会减少5-HT 神经元活动，这反过来又减少了烦躁的情感状态， 尤其是在AN。 新技术提供了直接表征动态 5-HT受体功能与人类行为的关系。短期内 （1至4岁），资助的研究将调查五组妇女18至45 年龄：1）患病的AN和BN女性; 2）康复的AN和BN女性（大于1 月经正常1年，无暴饮暴食和腹泻，体重健康稳定）; 3)健康对照组女性。在目标1中，150 PET成像和18-F-阿坦色林将 评估5-HT-2A突触后受体结合。初步数据支持 恢复的AN和BN妇女将有可能减少 眶额5-HT-2A受体发现与增加的证据相关 细胞外5-HT。增加2A发现和减少细胞外5-HT将 发生在患病的AN和BN受试者中。在Aim 2 150 PET成像和11-C-WAY 100635中 研究将评估5-HT-1A受体结合。小鼠中的敲除基因研究 支持突触前中缝自感受器功能障碍的假设 可能导致5-HT活性增加和行为症状。因此，1A 结合可能不随疾病状态而改变。Aim 3将测试核心 AN或BN症状或冲动控制与5-HT神经元活动有关。 为了充分表征5-HT的14个或更多个受体和其他组分， 神经元通路可能需要多种配体。长期（3 - 5年） 候选人寻求使用此K 05开发多中心协作 研究1）使用PET成像和放射性配体来全面表征 AN和BN中的5-HT和相关系统，以及2）开发与 5-HT的行为。此外，该K 05奖将支持培训 候选人，谁反过来将培训建立和年轻的调查人员在这些 新技术了解生物脆弱性，例如 5-HT紊乱，发生在AN和BN可能有助于发展新的 对这些慢性和致命疾病的治疗干预， 揭示了5-HT神经递质与行为的关系。

DESCRIPTION: Several lines of indirect evidence suggest that brain serotonin alterations occur in women with anorexia nervosa (AN) and bulimia nervosa (BN) when they are ill and after recovery. In theory, a trait-related increase of 5-HT neurotransmission may contribute to vulnerabilities (restricted feeding, obsessions with order and perfectionism, harm avoidance and negative affect) that contribute to developing AN and BN. In turn, malnutrition may reduce 5-HT neuronal activity, which in turn reduces dysphoric affective states, particularly in AN. New technologies offer the potential of direct characterization of dynamic relations between 5-HT receptor function and human behavior. In the short term (years 1 to 4), funded studies will investigate five groups of women 18 to 45 years old: 1) ill AN and BN women; 2) recovered AN and BN women (greater than 1 year normal menses, no binging and purging, and healthy and stable weight); and 3) healthy control women. In Aim 1, 150 PET imaging and 18-F-altanserin will assess 5-HT-2A postsynaptic receptor binding. Preliminary data support the possibility that recovered AN and BN women will have a reduction of orbitofrontal 5-HT-2A receptor finding associated with evidence of increased extracellular 5-HT. Increased 2A finding and decreased extracellular 5-HT will occur in ill AN and BN subjects. In Aim 2 150 PET imaging and 11-C-WAY100635 studies will assess 5-HT-1A receptor binding. Knockout gene studies in mice support the hypothesis that a malfunction of pre-synaptic raphe autoreceptors could contribute to increased 5-HT activity and behavioral symptoms. Thus, 1A binding may not change with state of the illness. Aim 3 will test whether core AN or BN symptoms or impulse control are related to 5-HT neuronal activity. To fully characterize the 14 or more receptors and other components of the 5-HT neuronal pathways may require multiple ligands. In the long term (years 3 to 5) the candidate seeks to use this K05 to develop a multicenter collaborative study to 1) use PET imaging and radioligands to comprehensively characterize 5-HT and related systems in AN and BN and 2) develop rodent models relating 5-HT to behavior. In addition, this K05 award will support training the candidate, who in turn will train established and young investigators in these new technologies. Understanding whether biologic vulnerabilities, such as a 5-HT disturbance, occurs in AN and BN may contribute to developing a new treatment interventions for these often chronic and deadly disorders as well as shed light on the relation of 5-HT neurotransmission and behavior.