Serotonin 1B Receptor Imaging in Major Depressive Disorder

重度抑郁症的血清素 1B 受体成像

• 批准号: 7471793
• 负责人: ALEXANDER NEUMEISTER
• 金额: $ 16.39万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-14 至 2010-01-22
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7471793
• 关键词: Animals; Antidepressive Agents; Anxiety; Applications Grants; Area; Attention; Binding; Binding Sites; Biological Markers; Biology; Brain; Chemicals; DSM-IV; Data; Development; Disease; Disease Progression; Dose; Emotions; Foundations; Functional disorder; Future; Globus Pallidus; Hormones; Human; Image; Individual; Injection of therapeutic agent; Learning; Magnetic Resonance Imaging; Major Depressive Disorder; Measures; Methods; Modeling; Monitor; Mood Disorders; Neurons; Neurotransmitters; Pathogenesis; Patients; Pharmaceutical Preparations; Phenotype; Play; Positron-Emission Tomography; Process; Relative (related person); Rest; Risk; Role; Serotonin; Serotonin Receptor 5-HT1B; Serotonin Receptor Binding; Severities; Sleep; Stress; Symptoms; Therapeutic Agents; Therapeutic Effect; Time; Treatment Efficacy; Work; base; brain cell; cortico-limbic circuits; depressed; depression; design; drug development; in vivo; interest; mood regulation; neurotransmitter release; novel; novel therapeutics; public health relevance; radioligand; radiotracer; receptor; receptor binding; receptor function; sex

DESCRIPTION (provided by applicant): The serotonin type 1B (5-HT1B) receptor has been implicated in the pathogenesis of major depressive disorder (MDD). Highest concentrations of 5-HT1B receptors are found in the globus pallidus in humans. The globus pallidus has received attention recently given its functional and anatomical connection to the mesolimbic circuit which is believed to be involved in the pathophysiology of MDD. Abnormal modulation of neurotransmitter release as a consequence of dysfunctional 5-HT1B receptors in the neuronal circuits which have been shown to play a role in the pathophysiology of MDD may at least partially explain the potential neurophysiologic dysfunction underlying depression. The 5- HT1B receptor may also be a candidate target for drug development. Even though animal studies and studies in human suggest an important role for the 5-HT1B receptor in the pathogenesis of MDD it is not clear at all whether such models constitute relevant models for MDD in humans. The selective 5-HT1B receptor radioligand, [11C] CE-142,943, permits for the first time in vivo assessment of central 5-HT1B receptor binding using positron emission tomography (PET). This proposal is a 2-year study involving 10 medication-free, symptomatic subjects with current MDD according to DSM-IV criteria, and 10 individually matched healthy control subjects. All subjects will undergo one magnetic resonance imaging (MRI) scan, and one [11C] CE-142,943 PET scan under resting conditions. This study will provide important new information about the role of 5- HT1B receptors in the pathophysiology of MDD. Moreover, we believe that this study will generate important novel results which we plan to use as basis for subsequent studies that aim to determine the abnormal processes which underlie mood disorders, guide initial dosing of new therapeutic agents and that are central to predict symptom onset, monitor disease progression and assess the efficacy of therapeutic agents. PUBLIC HEALTH RELEVANCE: The neurotransmitter serotonin plays an important role in the development of depression. Serotonin is one of the brain's natural chemicals. Serotonin binds to serotonin receptors (binding sites) type 1B on brain cells to regulate emotion, anxiety, sleep, and stress hormones. With the use of positron emission tomography (PET) and administration of a radiotracer, we are able to measure the number of serotonin 1b receptors in the brain. Following the injection of the radiotracer, the PET scanner will detect the radiotracer present in brain areas. This information will be used to create pictures of the brain showing the distribution of serotonin type 1B receptors in the brain. This method allows to determining whether people with depression show a different number of serotonin 1b receptors in the brain as compared to healthy people without depression or other psychiatric illnesses. This study will help not only to learning more about the biology of depression, but may ultimately help to find better treatments for people with depression.

描述(由申请人提供)：5-羟色胺1B(5-HT1B)受体与严重抑郁障碍(MDD)的发病机制有关。人类苍白球中5-HT1B受体的浓度最高。苍白球在功能和解剖上与中脑边缘环路有关，被认为与MDD的病理生理学有关，因此近年来受到人们的关注。神经回路中5-HT1B受体功能失调导致神经递质释放的异常调节，已被证明在MDD的病理生理学中起作用，至少部分解释了抑郁症潜在的神经生理功能障碍。5-HT1B受体也可能是药物开发的候选靶点。尽管动物研究和人类研究表明5-HT1B受体在MDD的发病机制中起着重要作用，但这些模型是否构成人类MDD的相关模型尚不清楚。选择性的5-HT1B受体放射性配基[11C]CE-142,943首次允许使用正电子发射断层扫描(PET)在体内评估中央5-HT1B受体的结合。这项建议是一项为期两年的研究，涉及10名根据DSM-IV标准患有当前MDD的无药物、有症状的受试者，以及10名单独匹配的健康对照组受试者。所有受试者将在静息条件下接受一次磁共振成像(MRI)扫描和一次[11C]CE-142,943 PET扫描。本研究将为5-HT1B受体在MDD病理生理学中的作用提供重要的新信息。此外，我们相信，这项研究将产生重要的新结果，我们计划将其用作后续研究的基础，这些研究旨在确定情绪障碍背后的异常过程，指导新治疗药物的初始剂量，并对预测症状出现、监测疾病进展和评估治疗药物的疗效至关重要。公共卫生相关性：神经递质5-羟色胺在抑郁症的发展中起着重要作用。5-羟色胺是大脑的一种天然化学物质。5-羟色胺与脑细胞上的5-羟色胺受体(结合部位)1B结合，调节情绪、焦虑、睡眠和压力荷尔蒙。通过正电子发射断层扫描(PET)和放射性示踪剂的应用，我们能够测量大脑中5-羟色胺1b受体的数量。注射放射性示踪剂后，PET扫描仪将检测大脑区域中存在的放射性示踪剂。这些信息将被用来创建大脑的图片，显示5-羟色胺1B受体在大脑中的分布。这种方法可以确定与没有抑郁症或其他精神疾病的健康人相比，抑郁症患者大脑中的5-羟色胺1b受体是否有不同的数量。这项研究不仅有助于更多地了解抑郁症的生物学知识，而且最终可能有助于为抑郁症患者找到更好的治疗方法。