Probing Systems-Level Function of Fronto-Temporal

探测额颞叶的系统级功能

• 批准号: 7490652
• 负责人: JACK M. GORMAN
• 金额: $ 108.55万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7490652
• 关键词: Amygdaloid structure; Anxiety; Anxiety Disorders; Basic Science; Biological; Brain-Derived Neurotrophic Factor; Catechols; Clinical; Cognitive Therapy; Development; Disease; Emotional; Foundations; Fright; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Generalized Anxiety Disorder; Genes; Genotype; Grant; Hippocampus (Brain); Hydrocortisone; Image; Light; Magnetic Resonance Imaging; Measures; Outcome Measure; Panic Disorder; Patients; Pattern; Pharmaceutical Preparations; Post-Traumatic Stress Disorders; Prefrontal Cortex; Randomized; Range; Rate; Safety; Scanning; Serotonin; Stimulus; Stress; Structure; Symptoms; System; Therapeutic; Time; Transferase; Translating; Trauma; Treatment outcome; Week; Work; clinical Diagnosis; clinically relevant; endophenotype; neurobehavioral; pre-clinical; response; reuptake; serotonin transporter

GRANT=P50MH58911-06-0006 In the initial funding period for this Center, the aim of this project was to identify and characterize systems-level pathophysiology of two major, fear-related disorders using fMRI probes of fear circuitry in a manner complementary to the work in the basic science Projects. Untreated patients with PTSD and panic disorder, and normal control subjects, have been scanned during an instructed fear (anticipatory anxiety) paradigm and an emotional/anxiety work paradigm, representing non-verbal and verbal, translated and disease-oriented probes of fear circuitry. Distinct patterns and time courses of activity in amygdala, hippocampus and ventromedial prefrontal cortex were identified in association with fear, trauma and safety-related stimuli and contexts, for specific diagnosis, clinical features and cortisol profiles. Such work identifying biological sub-types and markers is most relevant when it can inform treatment mechanisms, development, selection, or response prediction. Therefore, a critical next step is to build upon and extend these studies in a manner that will enable us to further relate preclinical to clinical observations, and to make contributions to anxiety disorder therapeutics. Patients with PTSD and panic disorder will be randomized to either serotonin reuptake (SRI) medication or cognitive behavioral therapy (CBT), and studied immediately before and after 12 weeks of treatment using the two fMRI paradigms, structural MRI imaging, cortisol and autonomic measures, neurobehavioral measures, and clinical rating scales. Trauma ?exposed/PTSD negative subjects and normal control subjects will be studied with identical paradigms and intervals with generalized anxiety disorder(GAD), which provides a different anxiety symptom profile, will be studied once with these paradigms. Directed analyses will thus allow the further localization and characterization of frontal and limbic function and structure, specifically related to this broadening range of anxiety disorders, symptoms, treatments and outcome measures. In light of other recent scientific developments, serotonin transporter (5-HTT), brain derived neurotrophic factor (BDNF), MAO A and B, and catechol-0-methyl transferase (COMT) genotyping will be carried out on all subjects as well. This will provide an initial foundation for examining the relationships between the status of these genes and abnormal stress and fear responses, as well as identifying the patterns of fear circuitry activity that may represent clinically relevant endophenotypes.

授权= P50 MH 58911 -06-0006 在该中心的最初资助期间，该项目的目的是确定和表征两个主要的恐惧相关疾病的系统级病理生理学，使用功能磁共振成像探针的恐惧电路的方式补充基础科学项目的工作。 未经治疗的PTSD和惊恐障碍患者，和正常对照组，已被扫描期间指示的恐惧（预期焦虑）范式和情绪/焦虑的工作范式，代表非语言和语言，翻译和疾病为导向的探针的恐惧电路。杏仁核，海马和腹内侧前额叶皮层的活动的不同模式和时间过程中确定与恐惧，创伤和安全相关的刺激和背景，具体的诊断，临床特征和皮质醇配置文件。当识别生物亚型和标记物的工作可以为治疗机制、发育、选择或反应预测提供信息时，这种工作是最相关的。因此，关键的下一步是建立和扩展这些研究，使我们能够进一步将临床前观察与临床观察联系起来，并为焦虑症治疗做出贡献。PTSD和惊恐障碍患者将随机接受5-羟色胺再摄取（SRI）药物治疗或认知行为治疗（CBT），并在治疗12周之前和之后立即使用两种fMRI范式、结构MRI成像、皮质醇和自主神经测量、神经行为测量和临床评定量表进行研究。创伤？暴露/PTSD阴性受试者和正常对照受试者将用相同的范例和间隔进行研究，广泛性焦虑症（GAD）提供不同的焦虑症状特征，将用这些范例进行一次研究。因此，定向分析将允许进一步定位和表征额叶和边缘系统的功能和结构，特别是与焦虑症，症状，治疗和结果测量的范围扩大。根据其他最新的科学发展，还将对所有受试者进行5-羟色胺转运蛋白（5-HTT）、脑源性神经营养因子（BDNF）、MAO A和B以及儿茶酚-O-甲基转移酶（COMT）基因分型。这将为研究这些基因的状态与异常压力和恐惧反应之间的关系以及确定可能代表临床相关内表型的恐惧回路活动模式提供初步基础。