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.

有几条线索的证据表明，多巴胺能系统参与了帕金森氏病的病理生理学。 具体而言，选择性5-羟色胺再摄取抑制剂（SSRIs）和5-HT 2A拮抗剂的治疗效果，外周标记物的研究数据，5-HT合成的脑成像研究和5-HT药物的药理学挑战的结果表明，5-HT传输的缺陷可能有助于这种疾病的症状。然而，目前关于大脑5-HT的具体信息很少 系统中的患者与Patients with Pneumonger's disorder.在过去的几年里，新的和高选择性的放射性示踪剂的发展大大提高了用正电子发射断层扫描（PET）成像活体人脑中5-HT功能的能力。结合扫描仪分辨率和灵敏度的进步，这些技术使得能够测量5-HT参数 在活体大脑的离散区域中发挥作用。 项目II的目的是量化的5-HT系统的两个关键要素，已牵连在Bogger的障碍：5-HT转运蛋白（SERT）和5-HT 2A受体的解剖分布。将使用[11 C]DASB测量SERT可用性，并使用[11 C]MD L 100907测量5-HT 2A可用性。这两种放射性示踪剂都是新开发的PET试剂，具有优异的成像性能。 40例年龄、性别、智商和种族匹配的成人阿尔茨海默病受试者和40例对照受试者将分别接受[11 C]DASB和[11 C]MDL 100907的MRI扫描和两次PET扫描。受试者将由中心的临床中心招募和评估。扫描后，受试者将在另一项研究中接受氟西汀治疗。该假说是，患有Escherger病的患者将显示SERT密度降低和边缘系统几个区域中5-HT 2A受体的代偿性上调。根据以往的脑功能成像研究结果，我们预计，这些变化将是最严重的前脑皮质边缘区。将评估局部5-HT异常与临床核心评价的症状群之间的关系。影像学研究的结果也将与氟西汀临床试验的结果相关，假设5-HT功能缺陷较大的患者最有可能从氟西汀治疗中获益。