Neurodevelopmental Pathways Linking Physical Abuse and Affective Dysregulation

标题 躯体虐待与情绪调节障碍的神经发育途径 项目摘要/摘要 暴露于身体虐待是在以后的生活中发展成情感障碍的一个重要的危险因素。 尽管这一重大的公共卫生问题已经得到了很好的研究和复制，但仍有许多不清楚的地方 将虐待与后来的抑郁和焦虑联系起来的机制。过去的工作主要依赖于自我 报告虐待措施，这可能具有重大和令人困惑的偏见。此外，以前的 专注于滥用后神经生物学改变的研究只检查了一种神经生物学 同一个体的风险标记(如脑功能，但不是脑结构)。在这里，我们的工作 利用作为匹兹堡青年研究的一部分收集的现有数据，这是一个纵向项目，随后是两个 从童年、青春期到成年的一群男孩。在最近的后续行动中， 收集了205名男性子组的神经成像数据。在这个项目中，我们将重点放在皮质边缘 与生理活动有关的回路(包括杏仁核、部分前额叶皮质和海马体) 虐待。这种大脑回路被理论上认为是情绪和社交信息处理的核心 抑郁症和焦虑症中的失调因素。确定这些联系的神经行为基础是 对于我们理解虐待的发展后遗症、抑郁症的出现和 虐待后的焦虑和旨在改善长期的干预策略的发展 身体虐待的影响。为此，该应用程序有两个具体目标。首先，我们将调查 神经生物学、身体虐待和情感性精神病症状之间的联系。我们假设 这种身体虐待将与杏仁核功能活动增强有关。我们还预测， 受虐待的人杏仁核功能活动增强，杏仁核腹内侧部减少 前额叶皮质的连通性将显示出最大程度的抑郁和焦虑。第二，我们的目标是 调查长期虐待对大脑皮质边缘结构和功能有何影响(再次评估 使用多种MRI方法)。为此，我们将使用潜在类建模和多变量MRI分析 检查杏仁核和腹内侧额前叶结构、功能和连通性差异的工具。通过 利用丰富的前瞻性纵向数据，我们或许能够更准确地描述 大脑组织的原理，更直接地将神经生物学与虐待经历联系起来。带着一个 儿童遭受虐待的数量令人震惊，对这些联系的调查是重要和及时的。我们的建议 这项工作为理解身体虐待的神经生物学后遗症提供了一个前所未有的机会。 这项工作还有助于回答基本的科学问题，例如环境体验 影响大脑的长期发育。此外，这项工作可以有力地帮助我们理解 与身体虐待有关的情绪失调。

Title Neurodevelopmental Pathways Linking Physical Abuse and Affective Dysregulation Project Summary/Abstract Exposure to physical abuse is a significant risk factor for the development of affective disorders later in life. Though this major public health issue has been well studied and well replicated, much remains unclear about the mechanisms connecting abuse and later depression and anxiety. Past work has primarily relied on self- report measures of maltreatment, which may have significant and confounding biases. Furthermore, previous research studies focused on neurobiological alterations after abuse have only examined one neurobiological marker of risk in the same individuals (such as brain function, but not brain structure). Here, our work leverages existing data collected as part of the Pittsburgh Youth Study, a longitudinal project that followed two cohorts of boys through childhood, adolescence, and into adulthood. At the most recent follow-up, neuroimaging data were collected on a subset of 205 men. For this project, we will focus on corticolimbic circuitry (including the amygdala, portions of the prefrontal cortex, and hippocampus) in relation to physical abuse. This brain circuitry is theorized to be central to processing of emotional and social information, core dysregulated elements in depression and anxiety. Identifying the neurobehavioral bases of these links is crucial to our understanding of the developmental sequelae of abuse, the emergence of depression and anxiety after maltreatment, and the development of intervention strategies aimed at ameliorating the long-term effects of physical abuse. To these ends, this application has two specific aims. First, we will investigate linkages between neurobiology, physical abuse, and symptoms of affective psychopathology. We hypothesize that physical abuse will be related to heightened amygdala functional activity. We additionally predict that abused individuals with heightened amygdala functional activity, as well as reduced amygdala-ventromedial prefrontal cortex connectivity will show the greatest levels of depression and anxiety. Second, we aim to investigate how the chronicity of abuse may impact corticolimbic brain structure and function (again, assessed with multiple methods of MRI). For this aim, we will use latent class-modeling and multivariate MRI analytic tools to examine differences in amygdala and ventromedial prefrontal structure, function, and connectivity. By leveraging rich prospective longitudinal data, we may be able to more accurately characterize foundational principles of brain organization, and more directly connect neurobiology to experiences of abuse. With an alarming amount of children suffering abuse, investigation of these links is important and timely. Our proposed work represents an unprecedented opportunity to understand the neurobiological sequelae of physical abuse. This work can also aid in answering basic science questions, such as how environmental experience influences long-term brain development. Furthermore, this work can powerfully inform our understanding of mood dysregulation in relation to physical abuse.