From Fear to Anxious Misery: Developing a Defense Circuit Dimensional Classifier

从恐惧到焦虑痛苦：开发防御电路维度分类器

基本信息

批准号：
8544498
负责人：
Peter J Lang
金额：
$ 40.65万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-12 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8544498
关键词：
Acute Amygdaloid structure Animals Anxiety Anxiety Disorders Asses Behavior Behavioral Biological Biological Markers Biological Testing Brain Characteristics Chemosensitization Classification Clinic Clinical Comorbidity Complex Conceptions DSM-IV Development Diagnosis Diagnostic Diagnostic and Statistical Manual Dimensions Disease Disease susceptibility Distress Dysthymic Disorder Educational workshop Emotional Evaluation Fright Functional Magnetic Resonance Imaging Generalized Anxiety Disorder Genetic Research Health Human Imagery Incidence Interview Learning Measures Mediating Medicine Memory Mental Depression Moods Motor National Institute of Mental Health Neurobiology Panic Disorder Pathology Patient Self-Report Patients Pattern Physiology Prevention Prosencephalon Psychopathology Questionnaires Reaction Recording of previous events Reflex action Reporting Research Research Proposals Sampling Stimulus Strategic Planning Stress Symptoms System Testing Treatment outcome Work base behavior observation effective therapy improved indexing novel outcome forecast public health relevance response success therapy development vector

项目摘要

DESCRIPTION (provided by applicant): Pathological anxiety is commonly "conceptualized as an exaggerated fear state in which hyper- excitability of fear circuits...is expressed as hypervigilance and increased behavioral responsivity to fearful stimuli" (e.g., Rosen et al., 1998)-essentially an amplification of normal fear/defense circuit function. However, our previous research has shown that anxiety patients differ substantially in fear reactivity, within and across diagnoses, as measured by the magnitude of the probe startle reflex during fear imagery challenge (Cuthbert et al., 2003; Lang, McTeague & Cuthbert, 2005, 2007; Lang & McTeague, 2009). Thus, specific phobics show robust probe startle potentiation during fear imagery, while patients with more complex disorders (e.g, panic disorder, generalized anxiety disorder) characteristically show blunted reflex responses. Importantly, similar differences are also found within DSM diagnoses: Overall, fear potentiation decreases as the symptom picture is progressively more severe, comorbid, with higher scores on measures of negative affectivity-despite ratings of high, often much higher, fear during challenge (McTeague, Lang, et al., 2009, 2010, 2011). Considering that research both with animals and humans confirms that fear-circuit activation (amygdala mediated) potentiates the startle reflex, our research invites the novel hypothesis that the defense circuit is compromised/dysregulated in highly distressed anxiety patients. Thus, we examine reactivity to a fear imagery challenge in a broad sample of patients as they present for treatment at our health-center affiliated Fear and Anxiety Disorders Clinic (FADC). Functional MRI (fMRI) is used to asses fear/defense circuit function during fear imagery challenge, testing the hypothesis that alterations in normal defense circuit function mediates a dimension of fear reactivity that ranges from hyper-reactivity to hypo-reactivity in probe startle magnitude. A second broad aim is to test the hypothesis that increased circuit dysregulation and reflex blunting are reliably related to increased self-reports indexing a dimension of negative affectivity, as well as inversely related to treatment outcome success. The general research plan is therefore to develop biological classifiers for a dimension of pathology that cuts across anxiety/mood spectrum disorders. The approach is consistent with the NIMH Research Domain Criteria initiative (e.g, as described by Insel & Cuthbert 2009) implemented in RFA- MH-12-100.

描述（由申请人提供）：病理焦虑通常“概念化为夸张的恐惧状态，在这种恐惧状态中，恐惧电路的过度兴奋性……表示为过度维护和对恐惧刺激的行为反应性的增加”（例如，Rosen等人，1998年） - 实际上是对正常恐惧/国防电路的扩增。但是，我们以前的研究表明，焦虑患者在恐惧反应性，内部和跨越诊断，如恐惧图像挑战期间的探针惊吓反射的幅度所衡量（Cuthbert等，2003； Lang，McTeague＆Cuthbert，2005，2007; Lang＆McTeague，2009）。因此，特定的恐惧症在恐惧图像中表现出强大的探针惊吓增强，而疾病更复杂的患者（例如，恐慌症，普遍焦虑症）的特征表现出钝性的反射反应。重要的是，在DSM诊断中也发现了类似的差异：总体而言，由于症状图像逐渐更严重，合并症，恐惧增强的降低，并且在挑战期间高，恐惧的恐惧的情况下，对负面情感范围的措施得分较高（McTeague，Lang，Lang，Lang等，等等，2009年，2010年，2010年，2011年）。考虑到对动物和人类的研究都证实，恐惧电路激活（杏仁核介导）增强了惊吓反射，我们的研究引起了以下新的假设：在高度困扰的焦虑症患者中，防御回路受到损害/失调。因此，我们在广泛的患者样本中检查了对恐惧图像挑战的反应性，因为他们在我们的卫生中心附属恐惧和焦虑症诊所（FADC）中进行治疗。功能性MRI（fMRI）用于评估恐惧图像挑战期间的恐惧/防御电路功能，检验了以下假设：正常防御电路功能的变化介导了恐惧反应性的维度，恐惧反应性的维度从高反应性到探针幅度中的气震量的低反应性。第二个广泛的目的是检验以下假设：增加的电路失调和反射钝化与增加的自我报告可靠地相关，从而索引了负面情感的维度，以及与治疗结果成功的不相反。因此，一般研究计划是为了开发生物学分类器的病理学维度，该病理学跨越了焦虑/情绪谱系障碍。该方法与NIMH研究领域标准倡议（例如Insel＆Cuthbert 2009）一致。