ETIOLOGICAL PROCESSES IN THE ONSET AND MAINTENANCE OF ADVERSE HEALTH OUTCOMES IN MALTREATED YOUTH

疾控中心估计，儿童受害者一生的经济负担总计为1240亿美元 虐待。大量文献支持虐待儿童和不良反应之间的积极联系 身体健康结果，包括心血管疾病、肥胖、糖尿病、肺癌、慢性疼痛、 头痛、性传播感染和自身免疫性疾病。然而，这些发现中的大多数 源自横断面、短期或成人回溯性研究设计，严重限制了科学研究 可信度和因果推论。此外，导致这种结果的假定病因过程仍然存在。 这在很大程度上是未知的，并不是每个受到虐待的儿童都会经历任何长期的健康影响， 这表明存在独特的风险和弹性途径。这种对基础知识的缺乏理解 赋予虐待儿童受害者风险或恢复能力的机制阻碍了翻译研究 其中可以开发或修改针对已识别通路的预防性干预措施，以努力 减少这些健康差距及其相应的医疗成本。项目1将提高这一点的严谨性 通过实施一项大型的前瞻性队列研究来检查 儿童虐待在多种病因过程中被认为在儿童虐待的发生和维持中发挥作用 对受害者的不利健康后果。通过与宾夕法尼亚州的大规模伙伴关系 公共服务部，项目1将招募1200名8-13岁的儿童(50%为男性)， 包括900名在过去一年中经历过确凿虐待的人(300名性虐待，300名 身体虐待和300名疏忽)，以及人口统计上匹配的对照组儿童(300名)。这些过程 生物嵌入(BE)在神经内分泌、自主神经、免疫、表观遗传和细胞(即， 线粒体和端粒生物学)水平将被视为儿童健康的机制，包括大脑 健康(即最佳神经发育轨迹)、行为和情绪健康以及身体健康。 心理社会和行为过程，如复原力(即学校参与度、自尊、家庭和 同伴支持、适应性应对、灵活性、认知能力、情绪调节和执行功能)； 健康的生活方式行为(即锻炼、睡眠、饮食、性态度和物质使用)；以及治疗 使用率将作为合理的可塑性因素进行审查，以缓解BE和健康之间的关系。 目标包括：(目标1)全面了解虐待儿童、生物 嵌入(BE)和运行状况；(目标2)测试BE如何独立运行以及如何与 解释虐待与健康状况之间关系的心理社会和行为因素；以及 (目标3)测试基因、性别、种族、青春期阶段和虐待类型对 在AIMS 1和2中测试的模型。

The CDC estimates a $124 billion aggregate lifetime economic burden incurred by victims of child maltreatment. A large literature supports positive associations between child maltreatment and adverse physical health outcomes including cardiovascular disease, obesity, diabetes, lung cancer, chronic pain, headaches, sexually-transmitted infections, and autoimmune diseases. However, the majority of these findings derive from cross-sectional, short-term, or adult retrospective study designs, severely limiting scientific credibility and causal inferences. Moreover, putative etiological processes leading to such outcomes remain largely unknown and not every child who has been maltreated will experience any long-term health effects, suggesting the presence of unique risk and resilience pathways. This lack of understanding in the basic mechanisms conferring risk or resilience for victims of child maltreatment has stymied translational research where preventative interventions targeting identified pathways can be developed or modified in an effort to reduce these health disparities and their corresponding healthcare costs. Project 1 will raise the rigor of this science and address critical gaps by implementing a large, prospective cohort study to examine the effects of child maltreatment on multiple etiological processes believed to play a role in the onset and maintenance of adverse health outcomes for victims. Through a large-scale partnership with the State of Pennsylvania's Department of Human Services, Project 1 will recruit a large cohort of 1200 children aged 8–13 (50% males), including 900 who experienced substantiated maltreatment within the past year (300 sexual abuse, 300 physical abuse, and 300 neglect), along with demographically matched control children (300). The processes of biological embedding (BE) at the neuroendocrine, autonomic, immunologic, epigenetic, and cellular (i.e., mitochondria and telomere biology) levels will be examined as mechanisms of child health, including brain health (i.e., optimal neurodevelopmental trajectories), behavioral & emotional health, and physical health. Psychosocial and behavioral processes such as resilience (i.e., school engagement, self-esteem, family and peer support, adaptive coping, flexibility, cognitive ability, emotion regulation, and executive functioning); healthy lifestyle behaviors (i.e., exercise, sleep, diet, sexual attitudes, and substance use); and treatment utilization will be examined as plausible malleable factors that mitigate the relationship between BE and health. Aims include: (Aim 1) a comprehensive understanding of the interplay among child maltreatment, biological embedding (BE), and health status; (Aim 2) testing how BE operates independently and in conjunction with psychosocial and behavioral factors to explain the relationship between maltreatment and health status; and (Aim 3) testing the moderating effects of genotype, gender, ethnicity, pubertal stage, and maltreatment type on models tested in Aims 1 & 2.