Investigating the Associations Between Safety Cue Learning and Trauma Exposure in Development

在整个生命周期中，特别是在儿童和青少年时期，遭受创伤的情况很普遍， 在美国，超过三分之二的儿童至少经历过一次创伤事件， 到16岁众所周知，暴露于创伤会导致精神病理学（例如，焦虑症， 创伤后应激障碍（Posttraumatic stress disorder）。因此，不仅要优化和设计新颖的 为遭受创伤影响的个人采取干预措施，但也要确定 创伤暴露会带来精神病理学风险，有助于风险识别和早期干预。的 对于患有焦虑和其他创伤相关疾病的成年人和青年人， 认知行为疗法（CBT）。基于暴露的CBT借鉴了消光原理 学习过程中，个体反复遇到与创伤事件有关的线索， 威胁或令人厌恶的结果，从而随着时间的推移消除他们的恐惧反应。灭绝的行为 在过去的几十年里，成年啮齿动物的学习及其支持神经回路已经被描绘出来 模型和人体样本。至关重要的是，来自发育研究的越来越多的跨物种证据表明 灭绝学习在整个发展过程中经历了关键的变化，特别是在青少年时期。 在此期间，灭绝学习减少。值得注意的是，这些行为变化与 支持恐惧学习和灭绝的额叶边缘回路的非线性变化。划定机制 因此，利用这些非线性变化来减少恐惧至关重要。我们建议 研究安全提示学习（SCL）作为一种潜在的新的和发展敏感的方法，以优化 减少创伤暴露、焦虑症或两者兼而有之的青年的恐惧。此外，鉴于其中一个 创伤暴露和心理病理学之间的联系机制包括威胁和安全学习，SCL 可能起到重要的机械作用。在目标1中，我将使用皮肤电导反应作为 生理反应，而参与者完成SCL任务，以检查创伤之间的关联 儿童、青少年和年轻人（8-30岁）的暴露和SCL， 焦虑在目标2中，我将研究创伤暴露与神经机制之间的联系， SCL，即大脑半球-额杏仁核回路，在同一样本中使用功能磁共振 显像对于目标1和2，我还将比较SCL和灭绝学习，并检查是否有任何 SCL和与创伤暴露相关的额边缘回路的年龄相关变化。最后， 在目标3中，我将测试SCL和相关的额边缘回路是否介导创伤与 儿童、青少年和年轻人的暴露和焦虑。总之，本研究的目的是 探讨SCL作为创伤暴露与焦虑之间联系的潜在机制，并将SCL作为一种新的 这是一种优化减少恐惧的方法，因此具有很高的临床相关性和未来的转化潜力。

Exposure to trauma throughout the lifespan, and in particular during childhood and adolescence, is prevalent, with more than two-thirds of all children in the United States having experienced at least one traumatic event by age 16. It is well-established that exposure to trauma can lead to psychopathology (e.g., anxiety disorders, posttraumatic stress disorder) in many individuals. Thus, it is imperative to not only optimize and devise novel interventions for individuals suffering from the effects of trauma, but also to identify the mechanisms by which trauma exposures confer risk for psychopathology to aid efforts in risk identification and early intervention. The primary treatment approach for both adults and youth with anxiety and other trauma-related disorders is exposure-based cognitive behavioral therapy (CBT). Exposure-based CBT draws on principles of extinction learning in which individuals repeatedly encounter cues relating to the traumatic event in the absence of the threat or aversive outcome, thereby extinguishing their fear response over time. The behavior of extinction learning and its supporting neural circuitry have been delineated in the last several decades in adult rodent models and human samples. Critically, growing cross-species evidence from developmental studies suggests that extinction learning undergoes key changes across development, and in particular during the adolescent period during which extinction learning is diminished. Notably, these behavioral changes coincide with nonlinear changes in frontolimbic circuitry that supports fear learning and extinction. Delineating mechanisms of fear reduction that leverage these non-linear changes is therefore of critical importance. We propose to investigate safety cue learning (SCL) as a potential novel and developmentally-sensitive approach to optimize fear reduction in youth with trauma exposure, anxiety disorders, or both. Furthermore, given that one of the mechanisms thought to link trauma exposure and psychopathology involves threat and safety learning, SCL may serve an important mechanistic role. In Aim 1, I will use skin conductance response as an index of physiological reactivity while participants complete a SCL task to examine the association between trauma exposure and SCL among children, adolescents, and young adults (8-30 years of age) with and without anxiety. In Aim 2, I will examine the associations between trauma exposure and the neural mechanisms of SCL, namely hippocampal-frontoamygdala circuitry, in the same sample using functional magnetic resonance imaging. For Aims 1 and 2, I will also compare SCL to extinction learning and examine whether there are any age-related changes in SCL and related frontolimbic circuitry that are associated with trauma exposure. Finally, in Aim 3, I will test whether SCL and related frontolimbic circuitry mediate the association between trauma exposure and anxiety in children, adolescents, and young adults. In summary, the aims of this study will investigate SCL as a potential mechanism linking trauma exposure and anxiety and examine SCL as a novel approach to optimize fear reduction, thus carrying high clinical relevance and future translational potential.