IMAGING SEROTONIN FUNCTIONING IN ASPERGER'S DISORDERS

亚斯伯格症中血清素功能的成像

• 批准号: 6670926
• 负责人: MARC A LARUELLE
• 金额: $ 20.57万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6670926
• 关键词: Asperger syndrome; autism; behavioral /social science research tag; bioimaging /biomedical imaging; child mental disorders; compulsive behavior; cooperative study; data management; human subject; limbic system; magnetic resonance imaging; patient oriented research; positron emission tomography; radiotracer; receptor expression; serotonin; serotonin receptor; serotonin transporter; sign /symptom

Several lines of evidence implicate the serotonergic system in the pathophysiology of Asperger's disorder. Specifically, the therapeutic effects of selective serotonin reuptake inhibitors (SSRIs) and 5-HT2A antagonists, data from studies of peripheral markers, brain imaging studies of 5-HT synthesis and the results of pharmacological challenges with 5-HT agents converge in suggesting that a deficit in 5-HT transmission might contribute to the symptoms of this illness. However, very little specific information is currently available regarding the brain 5-HT system in patients with Asperger's disorder. Over the last few years, the development of new and highly selective radiotracers has greatly increased the ability to image 5-HT function in the living human brain with Positron Emission Tomography (PET). Combined with progress in scanner resolution and sensitivity, these techniques enable the measurement of parameters of 5-HT function in discrete areas of the living brain. The aim of project II is to quantify the anatomical distribution of two key elements of the 5-HT system that have been implicated in Asperger's disorder: the 5-HT transporter (SERT) and the 5-HT2A receptor. SERT availability will be measured with [11C]DASB and 5-HT2A availability will be measured with [11C]MD L 100907. Both radiotracers are newly developed PET agents with excellent imaging properties. Forty adult subjects with Asperger's disorder and forty controls matched for age, gender, IQ and ethnicity will undergo an MRI scan and two PET scans with [11C]DASB and [11C]MDL 100907, respectively. Subjects will be recruited and evaluated by the Clinical Core of the Center. Following the scans, subjects will be treated with fluoxetine in another study. The hypothesis is that patients with Asperger's disorder will show reduced density of SERT and a compensatory upregulation of 5-HT2A receptors in several areas of the limbic system. Based on results of previous functional brain imaging studies, we anticipate that these changes will be most severe in forebrain cortico-limbic areas. The relationship between regional 5-HT abnormalities and symptom clusters as evaluated by the Clinical Core will be assessed. The results of the imaging studies will also be correlated with the results of a clinical trial with fluoxetine, with the hypothesis that patients who show larger deficits in 5-HT function will be the most likely to benefit from fluoxetine treatment.

多项证据表明血清素能系统与阿斯伯格症的病理生理学有关。 具体而言，选择性血清素再摄取抑制剂（SSRI）和 5-HT2A 拮抗剂的治疗效果、外周标志物研究的数据、5-HT 合成的脑成像研究以及 5-HT 药物的药理学挑战结果集中表明， 5-HT 传输缺陷可能会导致这种疾病的症状。然而，目前关于大脑 5-HT 的具体信息非常少 阿斯伯格症患者的系统。在过去几年中，新型高选择性放射性示踪剂的开发大大提高了利用正电子发射断层扫描 (PET) 对活人大脑中 5-HT 功能进行成像的能力。结合扫描仪分辨率和灵敏度的进步，这些技术能够测量 5-HT 的参数 在活体大脑的离散区域中发挥功能。 项目 II 的目的是量化与阿斯伯格症有关的 5-HT 系统的两个关键元件的解剖分布：5-HT 转运蛋白 (SERT) 和 5-HT2A 受体。 SERT 可用性将使用 [11C]DASB 测量，5-HT2A 可用性将使用 [11C]MD L 100907 测量。两种放射性示踪剂都是新开发的 PET 试剂，具有出色的成像特性。 四十名患有阿斯伯格症的成年受试者和四十名年龄、性别、智商和种族相匹配的对照者将分别接受使用 [11C]DASB 和 [11C]MDL 100907 的 MRI 扫描和两次 PET 扫描。受试者将由中心的临床核心招募和评估。扫描后，受试者将在另一项研究中接受氟西汀治疗。假设患有阿斯伯格症的患者会表现出 SERT 密度降低以及边缘系统多个区域 5-HT2A 受体的代偿性上调。根据之前的功能性脑成像研究结果，我们预计这些变化在前脑皮质边缘区域最为严重。将评估临床核心评估的区域 5-HT 异常与症状群之间的关系。影像学研究的结果还将与氟西汀临床试验的结果相关联，假设 5-HT 功能表现出较大缺陷的患者最有可能从氟西汀治疗中受益。