Early Traumatic Stress Exposure: Neurodevelopmental Mechanisms of Clinical Risk

描述(由申请人提供)：早期接触极端应激源被认为会通过创伤过程对神经发育的影响而显著增加儿童发育性精神病的风险。这项建议的目的是阐明一种特别常见和有害的早期创伤应激的神经发育和临床后遗症，即家庭暴力暴露。父母间暴力和针对儿童的暴力都与增加临床风险有相当大的经验联系，正如临床和社区样本中的宽带外在化和内在化问题以及创伤后应激症状所表明的那样。神经科学研究使用小样本的极端群体对比(例如，比较受虐待儿童和未受虐待儿童)的最新证据，为假设暴力暴露发挥其影响的候选神经发育机制提供了坚实的经验基础，包括情绪认知处理的非典型模式，反映出对愤怒和威胁线索的高度敏感性。在这项基础性工作的基础上，我们采用以社区为基础的抽样方法，沿着家庭暴力暴露的全范围扩大和扩展这项工作，并在关键的幼儿期向更广泛的人口测试应用程序。具体目标是：(1)用维度方法确定家庭暴力暴露的最佳尺度，该方法反映了儿童暴力暴露的严重程度和形式的变化(从规范到极端)；(2)测试暴力暴露程度与学龄前儿童破坏性行为、焦虑和损害的特定模式的关系；以及(3)测试非典型情绪处理特征是否在暴露程度与精神病理症状和功能之间的联系随着时间的推移而中介，并确定这些模式是特定于暴力暴露还是更普遍的应激影响。我们利用了一个大的儿科样本(N=2,200)，以确定最近资助的关于学龄前儿童破坏性行为的发展敏感特征的MAPS研究(R01MH082830，Wakschlag，PI)。从社会人口学分层的地图队列中，我们抽取了一个样本(N=300)，其中家庭暴力暴露和非暴力家庭压力源丰富，但在其他方面代表了总体分层。在MAP研究的过程中，将采用多信息者、多方法、发展敏感的方法，在基线实验室访问和6个月的随访中评估学龄前儿童的破坏行为和焦虑。在第二次实验室访问中，将通过深入访谈评估家庭暴力暴露，并使用神经认知任务(例如，情感点探测)评估学龄前儿童的情绪处理。在使用事件相关电位(ERPs)对160名儿童进行面部处理的过程中，将直接评估大脑的反应模式。这一方法有望阐明创伤应激暴露在精神病理学出现中的作用，并为广泛适用的新干预措施提供基础，从而减轻与早期创伤经历相关的精神障碍的负担。 公共卫生相关性：拟议的研究采用了一种转换视角，将基于人群的方法与神经科学范式相结合，以表征家庭暴力暴露的维度谱，从而能够测试假定的神经发育机制及其与幼儿新出现的精神病理学的联系。这一研究路线为追踪早期经历如何影响大脑提供了一个广泛有用的范式：与神经精神障碍发展的长期影响的行为关系，包括创伤后应激障碍和其他焦虑障碍、破坏性行为障碍以及必然的双相情感障碍和其他情绪障碍。

DESCRIPTION (provided by applicant): Exposure to extreme stressors in early life is thought to substantially increase the risk of developmental psychopathology in children through effects of trauma processes on neurodevelopment. The aim of this proposal is to elucidate the neurodevelopmental and clinical sequelae of one particularly common and pernicious form of early traumatic stress, i.e., family violence exposure. Both inter-parental violence and child- directed violence have considerable empirical linkage to increased clinical risk, as indicated by broad-band externalizing and internalizing problems and post-traumatic stress symptoms in clinical and community samples. Recent evidence from neuroscientific studies using small samples of extreme group contrasts (e.g., comparing maltreated vs. non-maltreated children) provides strong empirical grounding for postulating candidate neurodevelopmental mechanisms by which violence exposure exerts its effects, including atypical patterns of cognitive processing of emotion reflecting heightened sensitivity to anger and threat cues. Building on this foundational work, we employ a community-based sampling approach to amplify and extend this work along the full spectrum of family violence exposure and test applications to the broader population during the critical early childhood period. Specific aims are to: (1) identify the optimal scaling of family violence exposure with a dimensional approach, which reflects variations in severity and forms of child violence exposure (from normative to extreme); (2) test the relationship of extent of violence exposure to specific patterns of preschool disruptive behavior, anxiety, and impairment; and (3) test whether atypical emotion processing characteristics mediate the link between exposure extent and psychopathology symptoms and functioning over time and establish whether these patterns are specific to violence exposure or are a more general effect of stress. We capitalize on a large pediatric sample (N=2,200) to be ascertained for the recently funded MAPS study on developmentally-sensitive characterization of preschool disruptive behavior (R01MH082830, Wakschlag, PI). From the sociodemographically stratified MAPS cohort, we draw a sample (N=300) enriched for family violence exposure and non-violent family stressors, but otherwise representative of the overall stratification. Parallel to the procedures of the MAPS study, a multi-informant, multi-method, developmentally-sensitive approach will be employed to assess preschool disruptive behavior and anxiety in a baseline laboratory visit and 6-month follow-up. In a second laboratory visit, family violence exposure will be assessed via an in-depth interview and preschoolers' emotion processing will be assessed with neurocognitive tasks (e.g., affective dot probe). Patterns of brain reactivity will be directly assessed during face processing using event-related potentials (ERPs) for a subset of 160 children. This approach shows promise for elucidating the role of traumatic stress exposure in the emergence of psychopathology and for providing a basis for broadly-applicable, novel interventions that can reduce the burden of mental disorder associated with early traumatic experiences. PUBLIC HEALTH RELEVANCE: The proposed study applies a translational perspective that combines a population-based approach to characterizing a dimensional spectrum of family violence exposure with neuroscientific paradigms that enable testing of putative neurodevelopmental mechanisms and their links to emergent psychopathology in young children. This line of inquiry provides a broadly useful paradigm for tracing how early experiences affect brain: behavior relations with long-term implications for the development of neuropsychiatric disorders including PTSD and other anxiety disorders, disruptive behavior disorders, and corollary bipolar and other mood disorders.