Anxiety, comorbidity, negative affect, and fear circuit activation

焦虑、合并症、负面情绪和恐惧回路激活

基本信息

批准号：
8466379
负责人：
Peter J Lang
金额：
$ 35.16万
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：
2012-05-04 至 2017-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8466379
关键词：
Advanced Development Affect Amygdaloid structure Animal Model Animals Anxiety Anxiety Disorders Automobile Driving Behavioral Biological Biological Models Brain Characteristics Chemosensitization Chest Pain Child Abuse Classification Clinical Comorbidity Cues Diagnosis Diagnostic Diagnostic and Statistical Manual Dimensions Disease Disease susceptibility Distress Dysthymic Disorder Electrocardiogram Emotional Fright Functional Magnetic Resonance Imaging Generalized Anxiety Disorder Goals Heart Human Imagery Incidence Internist Interview Laboratories Measures Mediating Medicine Memory Mental Depression Motor National Institute of Mental Health Neurobiology Neurosciences Organism Outcome Measure Pathology Patients Pattern Phenotype Post-Traumatic Stress Disorders Prevention Process Psychophysiology Questionnaires Reaction Recording of previous events Reflex action Regulation Reporting Research Sensory Process Severities Social Phobia Stimulus Stress Structure Subgroup Symptoms Trauma Treatment outcome Work autonomic reflex base effective therapy endophenotype improved novel novel strategies prognostic response social somatic reflex

项目摘要

DESCRIPTION (provided by applicant): Consistent with NIMH's Research Domain Criteria initiative (Insel & Cuthbert, 2009), the primary research goal is to advance the development of neurobiological measures of anxiety spectrum disorder, defining quantitative dimensions of pathology that advance understanding of the anxiety diathesis. The work's focus is the brain's amygdala-centered fear/defense circuit, as defined by basic laboratory neuroscience, which mediates a range of obligatory survival reflexes, including the potentiated startle response, and is generally held to be hyper-active in anxiety disorders. Our previous research indicates, however, that anxiety patients differ widely in their reflex reactivity during fear memory imagery (Cuthbert et al., 2003; Lang et al., 2005, 2007; Lang & McTeague, 2009). While most phobic patients show marked increases in probe startle magnitude during fear imagery, a high percentage of patients with more generalized anxiety disorders fail to show significant potentiation. Paradoxically, fear potentiation decreases progressively as the disorder is more severe, co-morbid, with greater negative affect-despite verbal reports of high, often much higher, fear during imagery (McTeague et al., 2009, 2010). Thus, we hypothesize a spectrum-wide, diagnosis cross-cutting dimension of fear-circuit regulation/dysregulation, and here use social anxiety disorder as a model system to elucidate the phenomenon, studying healthy controls and three social anxiety subtypes: circumscribed, generalized, and generalized social anxiety with depression, assessing circuit function directly with functional Magnetic Resonance Imaging (fMRI) as it relates to reflex reactivity in the psychophysiology laboratory. The specific aims are 1) to determine if activation of fear/defense circuit structures and their functional connectivity differ in response to narrative imagery challenges across social anxiety subtypes; 2) to directly assess the relationship between reflex reactivity and fear/defense circuit activatio patterns and a clinical symptom picture characterized by high co-morbidity, chronicity, and high negative affect; 3) to more broadly evaluate potential differences in emotional reactivity across social anxiety subtypes by assessing appetitive, as well as defensive reactivity using fMRI and psychophysiology, and 4) to evaluate the prognostic value of reflex and fear/defense circuit bio-markers measured during in initial assessment in predicting questionaire-based outcome measures of clinical status following treatment.

描述（由申请人提供）：与NIMH的研究领域标准倡议一致（Insel＆Cuthbert，2009年），主要的研究目标是促进焦虑谱障碍的神经生物学测量的发展，从而定义了病理学的定量维度，从而提高了对焦虑症状的理解。这项工作的重点是大脑以杏仁核为中心的恐惧/防御回路，这是由基本实验室神经科学定义的，它介导了一系列强制性的生存反射，包括增强的惊吓反应，并且通常认为在焦虑症中具有过度活跃。然而，我们先前的研究表明，焦虑患者在恐惧记忆图像期间的反射反应性有很大差异（Cuthbert等，2003； Lang等，2005，2007； Lang＆McTeague，2009）。虽然大多数恐惧症患者在恐惧影像中表现出惊人的幅度的显着增加，但更普遍的焦虑症患者的比例很高，无法显示出明显的增强性。矛盾的是，由于这种疾病更加严重，合并症，恐惧增强逐渐减少，并且具有更大的负面影响，因为尽管言语高（通常要高得多）在图像期间的恐惧较高（McTeague等，2009，2010）。 Thus, we hypothesize a spectrum-wide, diagnosis cross-cutting dimension of fear-circuit regulation/dysregulation, and here use social anxiety disorder as a model system to elucidate the phenomenon, studying healthy controls and three social anxiety subtypes: circumscribed, generalized, and generalized social anxiety with depression, assessing circuit function directly with functional Magnetic Resonance Imaging (fMRI) as it relates to reflex reactivity in the心理生理实验室。具体目的是1）确定恐惧/防御电路结构的激活及其功能连通性是否在跨社交焦虑亚型的叙事图像挑战的响应中有所不同； 2）直接评估反射反应性与恐惧/防御电路活动模式与临床症状图片之间的关系，其特征是高高的，慢性和高负面影响； 3）通过评估食欲和防御性反应性，使用fMRI和心理生理学来评估社交焦虑亚型的情绪反应性的潜在差异，以及4），以评估反射和恐惧/防御/防御/防御/防御巡回赛的预后价值，在预测基于问题的基于问题的评估中测量的基于问题的基于问题的评估的临床临床临床临床临床状况的初步评估。