Prospective Determination of Neurobehavioral Risk for the Development of Emotion Disorders

情绪障碍发展的神经行为风险的前瞻性测定

基本信息

批准号：
9250014
负责人：
ALEXANDER JOSEPH SHACKMAN
金额：
$ 75.52万
依托单位：
UNIV OF MARYLAND, COLLEGE PARK
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2021-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9250014
关键词：
19 year old Address Adolescence Amygdaloid structure Anterior Anxiety Anxiety Disorders Architecture Attention Base of the Brain Behavior Behavioral Biological Biological Assay Biological Markers Biological Neural Networks Biological Psychiatry Brain Brain imaging Clinical Clinical Psychology Communities Complex Cues Data Development Diagnosis Dimensions Disease Ecological momentary assessment Emotional Emotional disorder Emotions Enrollment Etiology Face Feeling Female Foxes Functional Magnetic Resonance Imaging Future Goals Gold Growth Heritability Image Imaging Techniques Individual Insula of Reil Intervention Interview Laboratories Life Life Stress Link Measures Mediator of activation protein Mental Depression Mental disorders Methodology Modeling Moods Names National Institute of Mental Health Nature Neurobiology Neurotic Disorders Neurotics Panic Pathologic Pathology Pathway interactions Patient Self-Report Phenotype Plant Roots Post-Traumatic Stress Disorders Prevention strategy Psychiatry Psychology Recommendation Recruitment Activity Recurrence Research Research Domain Criteria Risk Risk Factors Risk Marker Rodent Sampling Self Medication Shock Social isolation Social support Specificity Stress Structure of terminal stria nuclei of preoptic region Symptoms System Techniques Testing Time Withdrawal Work anxious base brain circuitry cingulate cortex clinically relevant clinically significant cost design early adolescence emerging adult emotional experience experience innovation insight mood symptom negative mood network models neural circuit neurobehavioral new therapeutic target novel phenotypic biomarker prevent prospective public health relevance racial diversity relating to nervous system response social stress symptom support network therapeutic development trait undue influence

项目摘要

DESCRIPTION (provided by applicant): Anxiety disorders and depression are common, costly, and often difficult to treat, underscoring the need to understand the biological mechanisms that confer elevated risk. Individuals with a neurotic-anxious (NA) disposition are particularly vulnerable to these debilitating emotional disorders during late adolescence and early adulthood. NA is a trait-like phenotype that is evident early in life, stable over time, heritable, and characterized by sustained levels of heightened anxiety in contexts where threat is uncertain, ambiguous, or remote. Although NA is among the most robust phenotypic risk markers for anxiety and depression, it remains unclear why individuals with elevated NA are more likely to experience emotional disorders. Recent work by our group and others suggests the hypothesis that elevated risk reflects alterations in the activity and functional connectivity f the brain networks supporting sustained anxiety. In particular, this work highlights the contributions of the bed nucleus of the stria terminalis (BNST) and cortical regions, such as the anterior insula (AI). Building on our productive track record of fMRI and ecological momentary assessment (EMA) research, our goal is to understand the contribution of sustained-anxiety circuitry to the development, intensification, and recurrence of clinically-significant internalizig symptoms using an innovative combination of advanced fMRI analytic techniques and longitudinal assessments of daily experience and clinical symptom dimensions. We will use well-established NA assays to phenotype >5,000 racially-diverse 18-19 year olds and enroll the full spectrum of phenotypic risk (without gaps), over-sampling those at greatest risk (120 high, 60 medium, 60 low NA; half female). At enrollment, fMRI will be used to probe brain networks involved in sustained as well as transient anxiety. Using EMA, daily experience will be intensively sampled at 0, 6, 24, and 30 months, enabling an unprecedented longitudinal assessment of mood, function, and pathology-promoting behaviors and affording the first opportunity to explore the real-world significance of NA-related intermediate phenotypes. Diagnoses, dimensional symptoms, and life stress will be assessed via gold-standard interview techniques at 0, 15, and 30 months. These data would enable us to: (1) discover the neural bases of phenotypic risk and develop risk (NA) biomarkers, (2) understand the contribution of the BNST, AI, amygdala, and other anxiety- sensitive circuitry to the future progression of stress-sensitive, clinically-significant internalizing symptoms and diagnoses, and (3) understand the contribution of sustained-anxiety circuitry to the emergence of pathology- promoting feelings and behaviors in daily life. These objectives are closely aligned with the NIMH Strategic Objectives and RDoC initiative. This project would provide a potentially transformative opportunity to identify the distributed neural networks most relevant to transdiagnostic risk and most predictive of internalizing symptoms, inform our understanding of etiology, and guide the development of novel translational models and more precise intervention strategies.

描述（由适用提供）：焦虑症和抑郁症是普遍的，昂贵的且通常难以治疗的，了解需要了解赋予风险升高的生物学机制。具有神经性焦虑（NA）性格的个体在青少年和成年初期尤其容易受到这些使人衰弱的情绪障碍的影响。 Na是一种类似性状的表型，是生命早期的证据，随着时间的推移稳定，可遗传，其特征是在威胁不确定，模棱两可或遥不可及的情况下持续增强的焦虑。尽管NA是焦虑和抑郁症的最强大的表型风险标记之一，但尚不清楚为什么NA升高的人更有可能患有情绪障碍。我们小组和其他人的最新工作表明，升高的风险反映了大脑网络支持持续动画的活动的变化。特别是，这项工作突出了质末端（BNST）和皮质区域（例如前岛（AI））的床核的贡献。我们的目标是在我们的生产效果记录和生态瞬时评估（EMA）研究（EMA）的基础上，是了解持续存在的焦虑电路对临床上具有临床上有意义的内在符号的开发，强化和复发的贡献，该符号是对高级FMRI分析技术和较长的日常经验和临床经验经验和临床经验症状的创新组合。我们将使用良好的NA评估来> 5,000个大致多样化18-19岁的年轻人，并招募全部表型风险（没有差距），超过了那些具有最大风险的人（120个高，60个中等，60个中等，60个低NA；一半女性）。入学时，fMRI将用于探测涉及持续和短暂焦虑的脑网络。使用EMA，每天的经验将在0、6、24和30个月进行深入采样，从而实现了对情绪，功能和促进病理学行为的前所未有的纵向评估，并为探索NA与NA相关的中间体表型的现实世界中的意义提供了第一个机会。诊断，维符号和生命压力将通过0、15和30个月的金标准访谈技术评估。这些数据将使我们能够：（1）发现表型风险的神经基础并发展风险（NA）生物标志物，（2）了解BNST，AI，AI，杏仁核以及其他焦虑症的贡献，以及其他敏感的电路对应激敏感性，临床敏感的，临床上显着的内在症状和贡献（3）的贡献的未来进展，了解 - 3）日常生活中的感觉和行为。这些目标与NIMH的战略目标和RDOC计划紧密吻合。该项目将提供一个潜在的变革机会，以确定与转诊风险最相关的分布式神经元网络，并最终预测内化症状，告知我们对病因的理解，并指导新型翻译模型的发展和更精确的干预策略。