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.

授予=P50MH58911-06-0006 在该中心的初始资助期间，该项目的目的是使用恐惧回路的功能磁共振成像探针，以与基础科学项目工作互补的方式，识别和表征两种主要的恐惧相关疾病的系统级病理生理学。 未经治疗的创伤后应激障碍（PTSD）和恐慌症患者以及正常对照受试者在指导性恐惧（预期性焦虑）范式和情绪/焦虑工作范式中进行了扫描，代表了恐惧回路的非语言和语言、翻译和疾病导向的探索。杏仁核、海马体和腹内侧前额叶皮质的不同活动模式和时间过程被确定与恐惧、创伤和安全相关刺激和环境相关，用于具体诊断、临床特征和皮质醇概况。当此类识别生物亚型和标记物的工作能够为治疗机制、发展、选择或反应预测提供信息时，它是最相关的。因此，下一步关键是以这些研究为基础并加以扩展，使我们能够进一步将临床前与临床观察联系起来，并为焦虑症治疗做出贡献。患有 PTSD 和恐慌症的患者将被随机分配接受血清素再摄取 (SRI) 药物或认知行为治疗 (CBT)，并在治疗前和治疗后 12 周立即使用两种功能磁共振成像范式、结构 MRI 成像、皮质醇和自主测量进行研究，神经行为测量和临床评定量表。创伤暴露/PTSD 阴性受试者和正常对照受试者将使用相同的范式和时间间隔进行研究，而广泛性焦虑症（GAD）则提供了不同的焦虑症状特征，将使用这些范式进行一次研究。因此，定向分析将允许进一​​步定位和表征额叶和边缘功能和结构，特别是与扩大的焦虑症、症状、治疗和结果测量范围相关的功能和结构。鉴于其他最近的科学发展，血清素转运蛋白（5-HTT）、脑源性神经营养因子（BDNF）、MAO A和B以及儿茶酚-0-甲基转移酶（COMT）基因分型也将对所有受试者进行。这将为检查这些基因的状态与异常压力和恐惧反应之间的关系，以及识别可能代表临床相关内表型的恐惧电路活动模式提供初步基础。