PET IMAGING AND SEROTONIN LIGANDS IN EATING DISORDERS

描述：几行间接证据表明，大脑中的5-羟色胺 神经性厌食症(AN)和神经性暴食症(BN)的女性会发生改变 当他们生病时和康复后。从理论上讲，与性状相关的增加 5-羟色胺的神经传递可能导致脆弱性(限制进食， 痴迷于秩序和完美主义、避免伤害和负面影响) 这有助于发展AN和BN。反过来，营养不良可能会降低5-羟色胺 神经元活动，进而减少烦躁不安的情感状态， 尤其是在一个。 新技术提供了直接表征动态的可能性 5-羟色胺受体功能与人类行为的关系在短期内 (第1至第4年)，资助的研究将调查5组18至45岁的女性 年龄：1)患病的AN和BN妇女；2)康复的AN和BN妇女(大于1 月经正常，不暴饮暴食，体重健康稳定)； 3)健康对照妇女。在AIM 1,150 PET成像和18-F-Altanserin将 评估突触后5-羟色胺-2A型受体结合。初步数据支持 康复的AN和BN妇女的可能性将减少 眼眶前额叶5-羟色胺-2A型受体的发现与增加的证据相关 胞外5-羟色胺。增加2A发现和减少细胞外5-羟色胺将 多见于AN和BN受试者。在AIM 2 150 PET成像和11-C-WAY100635 研究将评估5-HT-1a受体的结合情况。小鼠基因敲除的研究 支持这样一种假设，即突触前中缝自身受体的功能障碍 可能导致5-羟色胺活性增加和行为症状。因此，1a 结合可能不会随着病情的变化而改变。目标3将测试核心 AN或BN症状或冲动控制与5-羟色胺神经元活动有关。 为了全面了解5-羟色胺的14个或更多受体和其他成分 神经通路可能需要多个配体。长期(第3至第5年) 候选人寻求利用这一K05来开发多中心协作 1)利用PET成像和放射性配基综合表征的研究 5-羟色胺及其相关系统在AN和BN中的作用和2)建立的啮齿动物模型 5-羟色胺对行为的影响。此外，这个K05奖项将支持培训 候选人，他将在这些方面培训成熟的和年轻的调查人员 新技术。了解生物脆弱性，例如 5-羟色胺紊乱，发生在AN和BN可能有助于开发新的 对这些通常是慢性和致命疾病的治疗干预以及 阐明了5-羟色胺的神经传递与行为的关系。

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.