Brain-Behavior Markers of Negative Affectivity, Comorbidity in Anxiety Disorders

 描述（由申请人提供）：焦虑症（AD）在神经功能障碍方面可能更相似而不是不同。检查独立于特定诊断的表型变异可能有助于解释AD中精神病理学的基本生物行为底物，从而改善分类和治疗。例如，AD中的合并症很常见，并且已知与情绪反应的严重程度和测量有关，例如自我报告的消极情感（NA），但其潜在的神经生物学证据很少。的 该K23的主要目标是为候选人提供大脑（功能性磁共振成像，fMRI）和行为（眨眼惊吓）负面情绪处理措施的培训，以启动候选人作为独立临床神经科学家的职业生涯，具有多层次，神经生物学，焦虑情绪功能障碍的维度分析。该提案有三个组成部分：1）具有互补专业知识的导师团队，2）填补候选人先前教育空白的教学方法，以及3）对候选人成长至关重要的实践经验。该研究计划测试的效用的维度transdiagnosis方法在连接神经和行为措施失调的负面情绪处理临床相关的焦虑负担，其特征在于共病负荷和自我报告的NA。该项目的参与者将包括90名患有“简单”恐惧症的成年人（特定恐惧症或仅表现社交焦虑）被招募以填充3种共病负荷单元：1）n = 30，无共病; 2）n = 30，有1种其他焦虑或抑郁（AnxDep）障碍;和3）n = 30例患有2种或2种以上其他AnxDep疾病，所有这些都与精神病学健康对照（HC，n = 30）进行了比较。该K23利用了导师Phan的NIH资助的R 01（MH 101497 [08/2013-07/2017]）研究的招募基础设施，但在实践中（不同的任务和扫描会话）和科学上是不同的。参与者将在以下过程中同时接受fMRI和肌电图（EMG）惊吓记录：a）预期;和B）对厌恶刺激的反应。本研究的目的是：（1）检验负性情绪加工的脑测量指标、共感负荷与NA之间的关系;（2）检验负性情绪加工的行为（惊吓）测量指标、共感负荷与NA之间的关系;（3）探讨负性情绪加工的大脑和行为测量与共病负荷和NA之间的相互关系。共病负荷是疾病负担的一个标志，有助于理解维度和分类内化的精神病理学。通过完成这个项目和协调的培训计划，候选人将建立在她以前的专业知识在事件相关电位（ERP）和焦虑出现作为一个多模态，神经生物学专家使用互补的，分层的方法（功能磁共振成像，ERP，惊吓），以缩小神经生物学和临床概况之间的差距，以改善诊断和指导新的治疗。

 DESCRIPTION (provided by applicant): Anxiety disorders (ADs) may be more similar than different in terms of neural dysfunction. Examining phenotypic variability that is independent of specific diagnoses may help explicate fundamental biobehavioral substrates of psychopathology in the ADs, leading to improved classification and treatment. For instance, comorbidity in the ADs is common and is known to relate to severity and measures of emotional reactivity such as self-reported negative affectivity (NA), yet evidence of its underlying neurobiology is scarce. The primary goal of this K23 is to provide the candidate with training in brain (functional magnetic resonance imaging, fMRI) and behavior (eyeblink startle) measures of negative emotion processing, in order to launch the candidate's career as an independent clinical neuroscientist with expertise in the multi-level, neurobiological, dimensional analysis of emotional dysfunction in anxiety. The proposal has three components: 1) a mentorship team with complementary expertise, 2) didactics to fill gaps in the candidate's previous education and 3) hands-on experience critical to the candidate's growth. The research plan tests the utility of a dimensional transdiagnostic approach in linking neural and behavioral measures of dysregulated negative emotion processing to clinically relevant anxiety burden characterized by comorbidity load and self-reported NA. Participants in the proposed project will comprise 90 adults with a 'simple' phobia (specific phobia or performance-only social anxiety) recruited to fill 3 comorbidity load cells: 1) n = 30 with no comorbidity; 2) n = 30 with 1 other anxiety or depressive (AnxDep) disorder; and 3) n = 30 with 2 or more other AnxDep disorders, all compared to psychiatrically healthy controls (HCs, n = 30). This K23 leverages the recruitment infrastructure of mentor Phan's NIH-funded R01 (MH101497 [08/2013-07/2017]) study, but is distinct practically (different tasks and scan sessions) and scientifically. Participants will undergo simultaneous fMRI and electromyographic (EMG) startle recording during: a) anticipation of; and b) response to aversive stimuli. Consonant with candidate's training goals in fMRI affective neuroscience, startle methodology and their clinical application to dimensional constructs relevant to ADs, the project's aims are to: 1) examine the relationship between brain measures of negative emotion processing, comorbidity load and NA; 2) examine the relationship between behavioral (startle) measures of negative emotion processing, comorbidity load and NA; and 3) examine the interrelationships between brain and behavioral measures of negative emotion processing in relation to comorbidity load and NA. Comorbidity load, a marker of disease burden, may aid understanding of dimensional and categorical internalizing psychopathology. Through completion of this project and the coordinated training plan, the candidate will build upon her prior expertise in event-related potentials (ERPs) and anxiety to emerge as a multi-modal, neurobiological expert using complementary, layered methodologies (fMRI, ERPs, startle) to close gaps between neurobiology and clinical profiles, in order to improve diagnosis and guide new treatments.