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
基本信息
- 批准号:7800890
- 负责人:
- 金额:$ 25.02万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-04-10 至 2012-03-31
- 项目状态:已结题
- 来源:
- 关键词:AffinityAmygdaloid structureAnteriorAnxietyAnxiety DisordersArtsBiologicalBlood PlateletsBrainBrain imagingClinicalComorbidityConsultCorpus striatum structureDataDevelopmentDiagnosisDiseaseDisease ProgressionDoseEtiologyFunctional disorderGrantHippocampus (Brain)HumanImageImaging TechniquesInterventionKnowledgeLigandsMajor Depressive DisorderMeasuresMediatingMental DepressionMethodsModelingMonitorMood DisordersMoodsNatureNeurobiologyNeurotransmittersPatientsPlayPositron-Emission TomographyPost-Traumatic Stress DisordersPreventiveProceduresProcessPsychopathologyRecording of previous eventsRegulationRelative (related person)ResearchResearch PersonnelResolutionRoleSerotoninSerotonin Receptor 5-HT1BSymptomsSystemTherapeutic AgentsTimeTranslatingTranslational ResearchTraumaVentral Striatumbasecingulate cortexcohortdensityimprovedin vivoinnovationinsightinterestneural circuitneurobiological mechanismnovelnovel therapeuticspatient populationpre-clinical researchpreclinical studypublic health relevanceradioligandradiotracerreceptorreceptor bindingresearch studytherapy developmenttransmission process
项目摘要
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(由申请人提供):过去几十年的研究一直试图阐明创伤后应激障碍(PTSD)和重度抑郁症(MDD)的神经生物学原因。最近,考虑到PTSD和重度抑郁症的高发率和在这类重症患者群体中发现的临床挑战,人们对两者之间的关系越来越感兴趣。基于配体的成像技术虽然更广泛地应用于创伤后应激障碍和重度抑郁症,但尚未用于系统地检查它们的共发性。这项转化研究旨在利用最先进的脑成像技术,包括高分辨率研究断层扫描(HRRT)上的正电子发射断层扫描(PET)和5-羟色胺(5-HT) 1B受体的新型放射配体,扩大目前对PTSD和MDD共存的神经生物学机制的了解。越来越多的证据表明,5-HT1B受体可能在情绪和焦虑障碍的病因学中发挥重要作用,也可能在它们的共同发生中发挥重要作用。5-HT1B受体在调节5-羟色胺(5-HT)传递、中皮质边缘回路功能以及情绪和焦虑障碍的病理生理中发挥核心作用。由于5-HT1B受体的选择性配体是最近才出现的,所以关于5-HT1B受体在这些疾病中的作用的知识仍然有限。因此,体内5-HT1B受体的密度和分布的定量可能为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)中心一直是开发5-HT1B受体选择性PET放射性示踪剂的先驱。我们建议首次将这一创新配体应用于PTSD和MDD的共发性研究。我们建议使用[11C]P943,一种选择性的、高亲和力的5-HT1B受体拮抗剂,研究5-HT1B受体结合电位(BPND)在PTSD合并重度抑郁症患者和无创伤史的重度抑郁症患者中的作用。我们还将他们的数据与在不同资助机制下收集的无重度抑郁症PTSD患者和健康对照者的数据进行比较。我们相信这项研究将产生重要的新结果,这将告诉我们与PTSD和MDD共病相关的神经生物学机制。此外,这项研究的结果有可能为专门针对共病症状的治疗程序的发展提供信息,指导新治疗剂的初始剂量,并对预测症状发作、监测疾病进展和评估治疗剂的疗效至关重要。公共卫生相关性:神经递质血清素在创伤后应激障碍(PTSD)和抑郁症的发展中起重要作用。通过使用正电子发射断层扫描(PET)和放射性示踪剂,我们能够测量大脑中血清素1B型受体的分布。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,大脑中血清素1b受体的数量是否不同。
项目成果
期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Reduced amygdala serotonin transporter binding in posttraumatic stress disorder.
- DOI:10.1016/j.biopsych.2011.07.003
- 发表时间:2011-12-01
- 期刊:
- 影响因子:10.6
- 作者:Murrough, James W.;Huang, Yiyun;Hu, Jian;Henry, Shannan;Williams, Wendol;Gallezot, Jean-Dominique;Bailey, Christopher R.;Krystal, John H.;Carson, Richard E.;Neumeister, Alexander
- 通讯作者:Neumeister, Alexander
Linking plasma cortisol levels to phenotypic heterogeneity of posttraumatic stress symptomatology.
- DOI:10.1016/j.psyneuen.2013.10.003
- 发表时间:2014-01
- 期刊:
- 影响因子:3.7
- 作者:Horn, Charlotte A. C.;Pietrzak, Robert H.;Corsi-Travali, Stefani;Neumeister, Alexander
- 通讯作者:Neumeister, Alexander
Translational evidence for a role of endocannabinoids in the etiology and treatment of posttraumatic stress disorder.
- DOI:10.1016/j.psyneuen.2014.10.012
- 发表时间:2015-01
- 期刊:
- 影响因子:3.7
- 作者:Neumeister, Alexander;Seidel, Jordan;Ragen, Benjamin J.;Pietrzak, Robert H.
- 通讯作者:Pietrzak, Robert H.
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ALEXANDER NEUMEISTER其他文献
ALEXANDER NEUMEISTER的其他文献
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{{ truncateString('ALEXANDER NEUMEISTER', 18)}}的其他基金
A mGlu2/3 agonist in the treatment of PTSD
mGlu2/3 激动剂治疗 PTSD
- 批准号:
8650643 - 财政年份:2014
- 资助金额:
$ 25.02万 - 项目类别:
Kappa Opioid Receptor Imaging in Anorexia
Kappa 阿片受体成像在厌食症中的应用
- 批准号:
8723892 - 财政年份:2013
- 资助金额:
$ 25.02万 - 项目类别:
Kappa Opioid Receptor Imaging in Anorexia
Kappa 阿片受体成像在厌食症中的应用
- 批准号:
8598346 - 财政年份:2013
- 资助金额:
$ 25.02万 - 项目类别:
CB1 Receptor PET Imaging Reveals Gender Differencesin PTSD
CB1 受体 PET 成像揭示 PTSD 中的性别差异
- 批准号:
8494093 - 财政年份:2012
- 资助金额:
$ 25.02万 - 项目类别:
CB1 Receptor PET Imaging Reveals Gender Differencesin PTSD
CB1 受体 PET 成像揭示 PTSD 中的性别差异
- 批准号:
8680371 - 财政年份:2012
- 资助金额:
$ 25.02万 - 项目类别: