Neurobehavioral mechanisms of parent-child extinction learning in adolescent PTSD

项目摘要 本研究的目的是阐明在儿童中亲子消退学习的神经行为机制。 早期青少年创伤后应激障碍值得注意的是，直接学习的恐惧消退的缺陷与成人PTSD有关。 然而，患有创伤后应激障碍的青少年生活在家庭系统中，这可能会影响他们消除创伤的能力 回忆事实上，创伤后父母与子女之间的异常恐惧传播是青少年的一个潜在风险因素 创伤后应激障碍此外，以创伤为中心的认知行为疗法（TF-CBT）， 儿童创伤后应激障碍，使用暴露疗法的儿童的创伤叙述，为青年和他们的照顾者。在这里， TF-CBT旨在通过以下方式促进儿童直接和间接消除与创伤相关的恐惧 父母建模然而，没有报告的研究已经检查了直接和间接的累积影响， 儿童创伤后应激障碍的恐惧消失最后，青年PTSD的诊断仍然依赖于DSM综合征， 标准，创造了建立客观的，基于生物学的诊断的巨大需求。这项创新性的研究 该计划将（1）识别直接/替代恐惧消退的生理障碍及其独特的 对青少年PTSD的贡献，（2）确定恐惧获得和直接/替代的神经基质 青少年PTSD中的灭绝学习，以及（3）使用机器学习恐惧获得的生物标志物， 直接/替代性消退对青少年创伤暴露和PTSD诊断进行分类。 这个跨学科的研究小组将招募40名非创伤性的典型发展（TD）青年，40名创伤性的， 暴露比较（TEC）的青年没有精神疾病，和80个无药物治疗的青年与创伤后应激障碍，年龄10-14， 沿着它们的主要繁殖父母。青少年和父母将经历恐惧习得，然后是一本小说 恐惧灭绝范式在这里，青年将经历两个灭绝训练条件：1）直接灭绝和2） 通过观察它们的父母完成灭绝训练来替代灭绝。父/子皮肤电导和 将在所有恐惧方案阶段期间测量皱眉肌EMG。此外，青年将完成所有的恐惧 在功能磁共振成像期间的阶段，以探测恐惧获得的神经基质，以及直接和替代灭绝。以下 生理和功能磁共振成像分析，一种深度进化机器学习方法将应用于青年 神经生理学恐惧指数来分类创伤和PTSD状态。主要分析将1）检查 青年人直接和替代性灭绝的生理标志物及其对PTSD的相对贡献，2） 检查青少年PTSD中直接和替代消退期间的神经异常，以及3）确定 添加替代灭绝标记是否增强了青年创伤的机器学习分类， 创伤后应激障碍。这个雄心勃勃的亲子灭绝学习计划有望产生第一个 一套全面的儿童创伤后应激障碍的神经生理学标志物，将允许客观，合理的 针对父母-子女的治疗，以改善受影响青年的结果。

Project Summary The goal of this proposal is to elucidate neurobehavioral mechanisms of parent-child extinction learning in early adolescent PTSD. Notably, deficits in directly learned fear extinction are implicated in adult PTSD. However, youth with PTSD live within the family system, which could impact their ability to extinguish trauma memories. Indeed, abnormal parent-child transmission of fear following trauma is a potent risk factor for youth PTSD. Furthermore, trauma-focused cognitive behavioral therapy (TF-CBT), the gold-standard treatment for pediatric PTSD, uses exposure therapy of the child's trauma narrative for both youth and their caregiver. Here, TF-CBT aims to promote extinction of trauma-related fear both directly in the child and vicariously through parent modeling. However, no reported studies have examined the cumulative impact of direct and vicarious fear extinction in pediatric PTSD. Finally, the diagnosis of PTSD in youth continues to rely on DSM syndromal criteria, creating a great need to establish objective, biologically based diagnoses. This innovative research program will (1) identify physiological impairments in direct/vicarious fear extinction and their unique contributions to adolescent PTSD, (2) identify the neural substrates of fear acquisition and direct/vicarious extinction learning in adolescent PTSD, and (3) use machine learning on biomarkers of fear acquisition and direct/vicarious extinction to classify trauma exposure and PTSD diagnosis in adolescents. This interdisciplinary research team will recruit 40 non-traumatized typically developing (TD) youth, 40 trauma- exposed comparison (TEC) youth without mental illness, and 80 medication-free youth with PTSD, ages 10-14, along with their primary caregiving parent. Youth and parents will undergo fear acquisition followed by a novel fear extinction paradigm. Here, youth will undergo two extinction training conditions: 1) direct extinction and 2) vicarious extinction by observing their parent complete extinction training. Parent/child skin conductance and corrugator EMG will be measured during all fear protocol phases. Additionally, youth will complete all fear phases during fMRI to probe neural substrates of fear acquisition, and direct and vicarious extinction. Following physiological and fMRI analyses, a deep evolutionary machine learning approach will be applied to youth neurophysiological fear indices to classify trauma and PTSD status. Primary analyses will 1) examine physiological markers of direct and vicarious extinction in youth and their relative contribution to PTSD, 2) examine neural abnormalities during direct and vicarious extinction in adolescent PTSD, and 3) determine whether adding vicarious extinction markers enhances machine learning classification of youth trauma and PTSD status. This ambitious program of parent-child extinction learning promises to yield the first comprehensive set of neurophysiological markers of pediatric PTSD that will allow for objective, rational targeting of treatment in the parent-child dyad to improve outcomes for afflicted youth.