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）： 战区的士兵面临着因战斗经验而产生潜在重大影响的高风险。战斗压力可以导致许多高度影响的情绪和认知状况，最明显的是创伤后应激障碍（PTSD），重度抑郁症（MDD）和轻度创伤性脑损伤（mTBI）。情感神经科学的主要目标是有效地识别定义精神障碍的神经基质。虽然横断面脑成像研究为主要精神障碍的机制提供了巨大的洞察力，但这些条件本质上是动态的，这些条件的动荡快照提供了一种有限的方法来了解症状的变化如何反映在潜在的大脑机制中。我们的应用程序试图使用一种方法，使用间隔9个月的3个会话来绘制这些动态条件随时间的变化，以测量具有显著战斗暴露的退伍军人的大脑处理动态。这种方法将能够更好地理解在MDD和mTBI的背景下，PTSD中涉及的神经系统的波动和动态。功能性磁共振成像（fMRI）允许测量特定过程中的血液动力学脑反应，例如预期与PTSD病理生理学相关的厌恶刺激。本申请的目的是确定描述PTSD的大脑机制，并确定这些机制如何预测不良的临床过程。我们认为，测量大脑对预期压力反应的动态变化可以结合PTSD，MDD和mTBI的临床过程的波动。相反，这些波动往往模糊了对大脑处理过程的理解。我们将通过以下三个具体目标来检验这一假设：（1）识别战斗相关PTSD的横断面神经生物标志物，并确定这些生物标志物是否足够敏感和特异;（2）确定基线时预期压力的大脑激活在多大程度上预测了随访时PTSD症状严重程度的变化;（3）确定特定候选神经生物标志物反映PTSD和关键共病疾病的临床过程的程度，以及这些区域如何差异地招募调节网络。在短期内，这项研究可能有助于在我们的退伍军人群体中开发这些疾病的发达神经模型。从长远来看，这项研究将为旨在确定候选神经生物标志物的研究奠定基础，这些生物标志物可以为治疗干预研究提供疾病过程的客观神经表征。