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.

几条证据示出了血清素能系统在阿斯伯格疾病的病理生理中。 具体而言，选择性5-羟色胺再摄取抑制剂（SSRIS）和5-HT2A拮抗剂的治疗作用，来自外围标记的研究的数据，对5-HT合成的脑成像研究的研究以及5-HT代理的药理挑战的结果，表明5-HT代理可能会导致5-HT的缺陷对这种疾病造成这种疾病的影响。但是，目前几乎没有有关大脑5-HT的具体信息 阿斯伯格障碍患者的系统。在过去的几年中，通过正电子发射断层扫描（PET），新的和高度选择性的放射性示例的发展大大提高了在活体脑中的5-HT功能的能力。结合扫描仪分辨率和灵敏度的进展，这些技术可以测量5-HT的参数 在生物大脑的离散区域发挥作用。 II项目的目的是量化与阿斯伯格疾病有关的5-HT系统的两个关键要素的解剖分布：5-HT转运蛋白（SERT）和5-HT2A受体。 SERT的可用性将使用[11C] DASB测量，并使用[11C] MD L 100907测量5-HT2A的可用性。这两个放射性示例都是具有出色成像特性的新开发的宠物代理。 有40名患有阿斯伯格障碍的成年受试者和40个对照组的年龄，性别，智商和种族将进行MRI扫描，并分别进行[11C] DASB和[11C] MDL 100907的PET扫描。受试者将由中心的临床核心招募和评估。扫描后，在另一项研究中将用氟西汀对受试者进行治疗。假设是，阿斯伯格障碍的患者将显示SERT的密度降低，并且在边缘系统的几个区域中，5-HT2A受体的补偿性上调。根据先前功能性脑成像研究的结果，我们预计这些变化在前脑皮质膜区域将最为严重。将评估临床核心评估的区域5-HT异常与症状簇之间的关系。成像研究的结果也将与氟西汀临床试验的结果相关，假设表现出5-HT功能缺陷的患者最有可能受益于氟西汀治疗。