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（由申请人提供）：焦虑症和抑郁症很常见，治疗费用昂贵，而且通常难以治疗，这强调了了解导致神经质焦虑（NA）倾向升高的生物学机制的必要性。青春期末期和成年早期的衰弱性情绪障碍是一种特征样表型，在生命早期就很明显，随着时间的推移稳定，具有遗传性，其特征是在威胁不确定的情况下持续水平的哮喘焦虑。尽管 NA 是焦虑和抑郁最有力的表型风险标记之一，但我们小组和其他人最近的研究表明，风险升高反映了这一假设：NA 升高的个体更容易出现情绪障碍。特别是，这项工作强调了终纹床核（BNST）和皮质区域（例如前岛叶（AI））的贡献。 fMRI 的高效记录和生态瞬时评估（EMA）研究，我们的目标是利用先进的功能磁共振成像分析技术和日常经验的纵向评估的创新组合，了解持续焦虑回路对临床显着的内在症状的发展、加剧和复发的贡献我们将使用成熟的 NA 测定法对超过 5,000 名种族多样化的 18-19 岁青少年进行表型分析，并纳入全谱表型风险（无间隙），对高风险人群进行过度抽样（120 名高 NA、60 名中NA、60 名低 NA；入组时，将使用功能磁共振成像 (fMRI) 来探测涉及持续性和短暂性焦虑的大脑网络。使用 EMA，日常体验将得到强化。在 0、6、24 和 30 个月时采样，能够对情绪、功能和病理促进行为进行前所未有的纵向评估，并为探索 NA 相关中间表型的现实世界意义提供了第一个机会。将在 0、15 和 30 个月时通过黄金标准访谈技术评估诊断、维度症状和生活压力。这些数据将使我们能够：(1) 发现表型风险的神经基础并开发风险 (NA) 生物标志物。，（2）了解 BNST、AI、杏仁核和其他焦虑敏感回路对压力敏感、具有临床意义的内化症状和诊断的未来进展的贡献，以及（3）了解这些目标与 NIMH 战略目标和 RDoC 倡议密切相关，该项目将为识别最相关的分布式神经网络提供潜在的变革机会。跨诊断风险和最能预测内化症状，告知我们对病因的理解，并指导新的转化模型和更精确的干预策略的开发。