Neurobehavioral Substrates Of Combat Stress: A Follow-Up Study

战斗压力的神经行为基础：一项后续研究

• 批准号: 9275444
• 负责人: ALAN N SIMMONS
• 金额: --
• 依托单位: VA SAN DIEGO HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-10-01 至 2017-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9275444
• 关键词: Affective; Amygdaloid structure; Anterior; Aversive Stimulus; Behavioral; Biological Markers; Brain; Brain imaging; Chronic; Classification; Clinical; Cognitive; Combat Disorders; Comorbidity; Cues; Data; Development; Diagnosis; Diagnostic; Disease; Disease model; Disease remission; Dorsal; Emotional; Follow-Up Studies; Foundations; Fright; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Healthcare; Image; Individual; Injury; Insula of Reil; Intervention; Intervention Studies; Investigation; Knowledge; Lead; Longitudinal Studies; Major Depressive Disorder; Maps; Measurement; Measures; Mental Depression; Mental disorders; Methodology; Methods; Nature; Neurobiology; Periodicity; Population; Post-Traumatic Stress Disorders; Process; Quality of Care; Recording of previous events; Recovery; Recruitment Activity; Research; Research Design; Residual state; Scanning; Scientific Advances and Accomplishments; Severities; Shapes; Soldier; Stress; Structure; Symptoms; System; Testing; Therapeutic Intervention; Time; Treatment outcome; Veterans; War; Work; affective neuroscience; base; biological adaptation to stress; cingulate cortex; clinical predictors; combat; depressive symptoms; experience; follow-up; hemodynamics; high risk; improved; insight; mild traumatic brain injury; neural model; neurobehavioral; neurodevelopment; neuromechanism; public health relevance; relating to nervous system; response; stress related disorder; therapeutic evaluation; therapy outcome; time use

DESCRIPTION (provided by applicant): Soldiers in the war zone are at high risk for potentially significant repercussions resulting from combat experiences. Combat stress can lead to a number of highly impactful emotional and cognitive conditions, most notably Posttraumatic Stress Disorder (PTSD), Major Depressive Disorder (MDD), and mild Traumatic Brain Injury (mTBI). The primary goal of affective neuroscience is to effectively identify the neural substrates that define mental disorders. While cross-sectional brain imaging research has provided enormous insight into the mechanisms of major mental disorders, these conditions are by nature dynamic and a snapshot of the turbulence of these conditions provides a limited methodology for understanding how changes in symptoms are reflected in the underlying brain mechanisms. Our application attempts to use an approach that maps these dynamic conditions over time using 3 sessions spaced 9 month apart to measure the dynamics in brain processing in Veterans with significant combat exposure. This approach will enable a better understanding of the fluctuation and dynamics of the neural systems involved in PTSD, in the context of MDD and mTBI. Functional magnetic resonance imaging (fMRI) allows for measurement of the hemodynamic brain response during specific processes, such as anticipation of aversive stimuli, which are relevant to the pathophysiology of PTSD. The goal of this application is to determine the brain mechanisms that delineate PTSD and determine how these mechanisms can predict poor clinical course. We posit that measurement of the dynamic change in brain response to anticipatory stress can incorporate the fluctuations clinical course of PTSD, MDD, and mTBI. Conversely, these fluctuations often obscure understanding of brain processing when assessed cross-sectionally. We will examine this hypothesis by pursuing the following three specific aims: (1) Identify cross- sectionally neural biomarkers of combat-related PTSD and determine if these biomarkers are sufficiently sensitive and specific; (2) Determine the extent to which brain activation to anticipatory stress at baseline predicts changes in PTSD symptom severity at follow-up and (3) Determine the extent to which specific candidate neural biomarkers reflect the clinical course of PTSD and key comorbid disorders and how these regions differentially recruit modulatory networks. In the short term, this research may contribute to the development of well-developed neural models of these disorders in our Veteran population. In the long term, this research will lay the foundation for studies aimed at determining candidate neural biomarkers that can provide an objective neural representation of disease course for therapeutic intervention studies.

描述（由申请人提供）： 战区中的士兵面临高风险，可能会导致战斗经历引起的潜在重大影响。战斗压力会导致许多高度影响力的情绪和认知状况，最著名的是创伤后应激障碍（PTSD），重度抑郁症（MDD）和轻度的脑损伤（MTBI）。情感神经科学的主要目标是有效识别定义精神障碍的神经底物。虽然横截面大脑成像研究为主要精神疾病的机制提供了巨大的了解，但这些疾病本质上是动态的，并且这些疾病的湍流的快照为理解症状的变化如何在潜在的大脑机制中反映出来提供了有限的方法。我们的应用程序尝试使用一种方法，该方法使用3个月间隔3个月间隔的3个会话来绘制这些动态条件，以测量具有显着战斗暴露的退伍军人的大脑加工动力学。在MDD和MTBI的背景下，这种方法将更好地理解PTSD中涉及的神经系统的波动和动力学。功能磁共振成像（fMRI）允许在特定过程中测量血流动力学的大脑反应，例如与PTSD的病理生理学有关的厌恶刺激的预期。该应用的目的是确定描绘PTSD的大脑机制，并确定这些机制如何预测临床过程不良。我们认为，测量大脑对预期应激反应的动态变化可以结合PTSD，MDD和MTBI的波动临床过程。相反，在对横截面进行评估时，这些波动通常会掩盖对大脑处理的理解。我们将通过追求以下三个特定目的来检验这一假设：（1）确定与战斗相关的PTSD的横截面神经生物标志物，并确定这些生物标志物是否足够敏感且具体； （2）确定在基线时大脑对预期应力的激活程度可预测随访时PTSD症状严重程度的变化，以及（3）确定特定候选神经生物标志物在多大程度上反映了PTSD和关键合并症的临床过程以及这些地区如何招募调节网络。在短期内，这项研究可能有助于在我们的退伍军人人群中发展这些疾病的发达神经模型。从长远来看，这项研究将奠定旨在确定候选神经生物标志物的研究基础，这些神经生物标志物可以为治疗干预研究提供疾病课程的客观神经代表。