Neurobehavioral Substrates Of Combat Stress: A Follow-Up Study

描述(由申请人提供)： 战区的士兵面临着战斗经历可能产生重大影响的高风险。战斗应激可导致许多高度影响的情绪和认知疾病，最明显的是创伤后应激障碍(PTSD)、严重抑郁障碍(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础。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，这些条件的动荡的快照为理解症状的变化如何反映在潜在的大脑机制中提供了有限的方法学。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，随时间映射这些动态条件，以测量具有显著战斗暴露的退伍军人的脑处理动态。这种方法将使我们能够更好地理解创伤后应激障碍所涉及的神经系统的波动和动态，在MDD和mTBI的背景下。功能磁共振成像(FMRI)可以测量特定过程中的脑血流动力学反应，如对厌恶刺激的预期，这与创伤后应激障碍的病理生理相关。这项应用的目标是确定描绘创伤后应激障碍的大脑机制，并确定这些机制如何预测糟糕的临床病程。我们假设，测量大脑对预期应激反应的动态变化可以纳入创伤后应激障碍、MDD和mTBI的波动临床病程。相反，当对大脑进行横断面评估时，这些波动往往会模糊对大脑处理的理解。我们将通过追求以下三个具体目标来检验这一假设：(1)确定与战斗相关的创伤后应激障碍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)确定大脑对基线预期应激的激活程度在多大程度上预测后续PTSD症状严重程度的变化；(3)确定特定的候选神经生物标志物在多大程度上反映创伤后应激障碍和关键共病的临床过程，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良好神经模型。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，这些候选神经生物标志物可以为治疗干预研究提供客观的疾病过程的神经表征。

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.