Neuroimaging correlates of impaired fear inhibition in PTSD

描述（由申请人提供）：创伤后应激障碍（PTSD）发生在一些人暴露于导致极端恐惧或无助的事件后。全世界战区的发生率和美国大城市中心暴力的普遍性，增加了暴露于创伤事件的可能性。在这些事件中幸存下来的人中，大约10%的人会发展出这种影响个人和家庭的衰弱性疾病。个体患者表现出不同症状群的程度可能不同，因此“一刀切”的治疗往往是不够的。这种个体差异可能与增加疾病易感性或阻碍治疗的生物风险因素有关。虽然基因和环境相互作用会增加个体患创伤后应激障碍的风险，但尚不清楚这些因素如何影响潜在的神经生物学，从而导致观察到的失调。创伤后应激障碍的特征是边缘系统的皮质控制受损，特别是杏仁核和海马体。我们发现，与PTSD症状严重程度相关的标志性生理标志之一是在安全条件下无法抑制恐惧反应。无论创伤类型如何，这种表型似乎都是一个强大的标志物，因为它在平民和战斗PTSD人群中都可以观察到。拟议的研究将利用这一可观察到的标记和创伤个体之间的个体差异来研究受损的恐惧抑制的结构和功能神经基础。通过比较这种生理表型的DSM定义的障碍的分析，该研究将使用一种创新的方法来理解PTSD的病理生理学。使用最先进的成像工具来微调参与恐惧抑制的大脑区域的大小、形状和功能的测量，将提供急需的对创伤脆弱性的个体差异的洞察。

DESCRIPTION (provided by applicant): Posttraumatic stress disorder (PTSD) occurs in some people after exposure to events that cause extreme fear or helplessness. The incidence of war zones worldwide and the prevalence of violence in large urban centers in the U.S., increases the likelihood of exposure to traumatizing events. Of those who survive such events, approximately 10% will develop this debilitating disorder that affects both the individual and thei family. Individual patients can vary in the degree to which they present with the different symptom clusters, such that a "one size fits all" treatment is often inadequate. This individual variation may be associated with biological risk factors that increase vulnerability to the disorde or impede treatment. While both genes and environment interact to increase an individual's risk of developing PTSD, it is unclear how the underlying neurobiology is shaped by these factors to result in the observed dysregulations. PTSD is marked by impaired cortical control of the limbic system, specifically the amygdala and hippocampus. We have found that one of the hallmark physiological markers associated with PTSD symptom severity is the inability to inhibit the fear response under safe conditions. This phenotype appears to be a robust marker regardless of trauma type, as it is observed in both civilian and combat PTSD populations. The proposed study will capitalize on this observable marker and individual variability among traumatized individuals to investigate the structural and functional neural underpinnings of impaired fear inhibition. By comparing analyses of this physiological phenotype to the DSM defined disorder, the study will use an innovative approach to understand the pathophysiology of PTSD. The use of state-of-the art imaging tools to fine- tune the measurements of size, shape, and function of the brain areas involved in fear inhibition will offer much-needed insight into individual differences in vulnerability to trauma.