Serotonin 1B Receptor Imaging in PTSD with and without Co-morbid Depression

伴有或不伴有抑郁症的 PTSD 患者的血清素 1B 受体成像

• 批准号: 7628239
• 负责人: ALEXANDER NEUMEISTER
• 金额: $ 16.12万
• 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: 2009-04-10 至 2010-01-22
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7628239
• 关键词: Affinity; Amygdaloid structure; Anterior; Anxiety; Anxiety Disorders; Arts; Biological; Blood Platelets; Brain; Brain imaging; Clinical; Consult; Corpus striatum structure; Data; Development; Diagnosis; Disease; Disease Progression; Dose; Etiology; Functional disorder; Grant; Hippocampus (Brain); Human; Image; Imaging Techniques; Intervention; Knowledge; Ligands; Major Depressive Disorder; Measures; Mediating; Methods; Modeling; Monitor; Mood Disorders; Moods; Morbidity - disease rate; Nature; Neurobiology; Neurotransmitters; Patients; Play; Positron-Emission Tomography; Post-Traumatic Stress Disorders; Preventive; Procedures; Process; Psychopathology; Recording of previous events; Regulation; Relative (related person); Research; Research Personnel; Resolution; Role; Serotonin; Serotonin Receptor 5-HT1B; Symptoms; System; Therapeutic Agents; Time; Translating; Translational Research; Trauma; Ventral Striatum; base; cingulate cortex; cohort; density; depression; improved; in vivo; innovation; insight; interest; neural circuit; neurobiological mechanism; novel; novel therapeutics; patient population; pre-clinical research; preclinical study; public health relevance; radioligand; radiotracer; receptor; receptor binding; research study; therapy development; transmission process

DESCRIPTION (provided by applicant): Research over the past decades has sought to elucidate the neurobiological causes of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). More recently, there is increasing interest into the relationship of co-morbid PTSD and MDD given their high rates of co-occurrence and the clinical challenges found in this severely ill patient population. Ligand-based imaging techniques, while more widely applied to PTSD and MDD alone, have not been utilized to examine systematically their co-occurrence. The proposed translational research study aims to expand current knowledge of the neurobiological mechanisms of the co-occurrence of PTSD and MDD using state-of-the-art brain imaging techniques with positron emission tomography (PET) on a high resolution research tomograph (HRRT) and a novel radioligand for the serotonin (5-HT) 1B receptor. A growing body of evidence suggests that the 5-HT1B receptor might play an important role in the etiology of mood and anxiety disorders, and potentially also in their co-occurrence. The 5-HT1B receptor plays a central role in the regulation of serotonin (5-HT) transmission, mesocorticolimbic circuitry functioning and in the pathophysiology of mood and anxiety disorders. As selective ligands for the 5-HT1B receptor have only recently become available, knowledge for the involvement of 5-HT1B receptors in these disorders is still limited. Thus, in vivo quantitation of the density and distribution of 5-HT1B receptors might provide important insights into mechanisms contributing to the co-morbidity of PTSD and MDD. The Yale Positron Emission Tomography (PET) Center has been a pioneer in the development of a PET radiotracer selective for 5-HT1B receptors. We propose to apply this innovative ligand to study for the first time systematically the co-occurrence of PTSD and MDD. We propose using [11C]P943, a selective, high affinity 5- HT1B receptor antagonist, to investigate 5-HT1B receptor binding potential (BPND) in PTSD subjects with co-morbid MDD and MDD subjects without history of trauma. We will also compare their data to cohorts of patients with PTSD without MDD and healthy control subjects which have been collected under a different grant mechanism. We believe that this study will generate important novel results which will inform us about the neurobiological mechanisms associated with co-morbid PTSD and MDD. In addition, the results derived from this research has the potential to inform the development of treatment procedures that are directed specifically to co-morbid symptoms, 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 post-traumatic stress disorder (PTSD) and depression. With the use of positron emission tomography (PET) and administration of a radiotracer, we are able to measure the distribution of serotonin type 1B receptors in the brain. This method allows to determining whether people with PTSD and depression show a different number of serotonin 1b receptors in the brain as compared to healthy people without PTSD and depression and people with only depression.

描述(申请人提供)：过去几十年的研究试图阐明创伤后应激障碍(PTSD)和严重抑郁障碍(MDD)的神经生物学原因。最近，人们对共病的创伤后应激障碍和MDD的关系越来越感兴趣，因为它们的高共发率和在这一重症患者群体中发现的临床挑战。基于配基的成像技术，虽然更广泛地应用于PTSD和MDD，但尚未被用于系统地检查它们的共存。这项拟议的转化性研究旨在利用最先进的脑成像技术，结合高分辨率研究断层扫描仪(HRRT)上的正电子发射断层扫描(PET)和5-羟色胺(5-HT)1B受体的新型放射配基，扩大对PTSD和MDD共存的神经生物学机制的现有知识。越来越多的证据表明，5-HT1B受体可能在情绪和焦虑症的病因中发挥重要作用，也可能在它们的共同出现中发挥作用。5-HT1B受体在调节5-羟色胺(5-HT)传递、中脑皮质边缘回路功能以及在心境和焦虑症的病理生理学中发挥重要作用。由于5-HT1B受体的选择性配体最近才出现，有关5-HT1B受体参与这些疾病的知识仍然有限。因此，在体内定量5-HT1B受体的密度和分布可能为了解PTSD和MDD共同发病的机制提供重要的见解。耶鲁大学正电子发射断层扫描(PET)中心是开发对5-HT1B受体具有选择性的PET放射性示踪剂的先驱。我们建议首次应用这一创新的配体系统地研究PTSD和MDD的共存问题。我们建议使用一种选择性的、高亲和力的5-HT1B受体拮抗剂[11C]P943来研究PTSD患者和无创伤病史的MDD患者的5-HT1B受体结合潜力(BPND)。我们还会将他们的数据与没有MDD的PTSD患者和健康对照组的队列进行比较，这些患者是在不同的拨款机制下收集的。我们相信，这项研究将产生重要的新结果，将告诉我们与PTSD和MDD共病相关的神经生物学机制。此外，这项研究得出的结果有可能为开发专门针对共病症状的治疗程序提供信息，指导新的治疗药物的初始剂量，这些治疗药物对预测症状出现、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-羟色胺在创伤后应激障碍(PTSD)和抑郁症的发展中起着重要作用。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5-羟色胺1B受体在大脑中的分布。这种方法可以确定患有创伤后应激障碍和抑郁症的人与没有创伤后应激障碍和抑郁症的健康人以及只有抑郁症的人相比，大脑中显示的5-羟色胺1b受体的数量是否不同。