Child Maltreatment: Innovative Methods for Probing Stress Regulatory Systems and Polygenic Moderation in Child Psychopathology

虐待儿童：探索儿童精神病理学中的压力调节系统和多基因调节的创新方法

• 批准号: 10397547
• 负责人: Elizabeth DiPaola Handley
• 金额: $ 7.65万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10397547
• 关键词: Adrenal Glands; Affect; American; Attention; Behavior; Biological; Child; Child Abuse; Child Abuse and Neglect; Child Development; Childhood; Complex; Development; Disease; Diurnal Rhythm; Employment; Endocrine; Endocrine system; Environment; Etiology; Failure; Family; Foundations; Functional disorder; Funding; Generations; Genes; Genetic; Genetic Polymorphism; Genotype; Grant; Health; Hormones; Human; Hydrocortisone; Hypothalamic structure; Individual; Intervention; Investigation; Justice; Knowledge; Life Cycle Stages; Measures; Mental Depression; Mental disorders; Methods; Mood Disorders; National Institute of Drug Abuse; National Institute of Mental Health; Neurosecretory Systems; Outcome; Pathogenicity; Pathway interactions; Pituitary Gland; Post-Traumatic Stress Disorders; Poverty; Prevention; Preventive; Process; Productivity; Psyche structure; Psychiatric Social Work; Psychopathology; Public Health; Publishing; Regulation; Research; Rewards; Risk; Risk Factors; Role; Sexual abuse; Social Policies; Societies; Statistical Models; Stress; Substance Use Disorder; System; Testosterone; Translational Research; Trauma; United States National Institutes of Health; Violence; Work; abuse neglect; addiction; antisocial behavior; base; biological adaptation to stress; cost; dehydroepiandrosterone; deprivation; economic cost; emotional abuse; experience; gene environment interaction; hypothalamic pituitary gonadal axis; hypothalamic-pituitary-adrenal axis; innovation; knowledge base; large datasets; maltreated children; maltreatment; novel; person centered; physical abuse; physical conditioning; polygenic risk score; psychologic; resilience; symptomatology; trait; traumatized children

Project Summary/Abstract. Child maltreatment, a form of violence inflicted on children, is a complex, insidious problem that, although occurring more frequently in families residing in poverty, cuts across all sectors of society. The human costs of child maltreatment are a litany of biological and psychological tragedies that may last a lifetime. The economic costs for American society are astronomical, with billions of dollars spent in psychiatric, social services, educational, and justice system costs, as well as lessened productivity for a generation of abused children. Discovering the processes underlying the development of psychopathology and resilience among maltreated children offers great promise for informing prevention, intervention, and social policy initiatives. A multiple levels of analysis approach is integral to understanding the diverse ways child maltreatment compromises health. Herein, we seek to capitalize on a large data set (N=1135) including comprehensive assessments of maltreated and demographically comparable nonmaltreated children. Outside the scope of the original NIH grants, additional biological measures (genotypes; DHEA and testosterone) were obtained with limited foundation support. Incorporating these biological measures and using innovative quantitative methods will allow us to significantly advance new knowledge of substantial public health significance. Extant genetic work associated with child maltreatment has largely been in the context of examining gene x environment interactions (GxE), focusing on single gene polymorphisms. Given the diverse forms of psychopathology associated with maltreatment, we posit that multiple polygenic risk composites exist that will interact with maltreatment to affect child outcomes. We intend to use person-centered methods to differentiate individuals sharing multiple common genetic polymorphisms involved in the stress response system, and to advance our understanding of complex polygenic x environment interactions in child maltreatment. We also plan to investigate the effects of child maltreatment experiences on stress responsive hormonal systems, specifically the Hypothalamic Pituitary Adrenal (HPA) and the Hypothalamic Pituitary Gonadal (HPG) axes. Whereas the HPA axis had received considerable attention in regard to the impact of child maltreatment, attention to the role of the HPG axis and the mutual co-regulation between these axes has been limited. We seek to expand understanding of dysfunction in these regulatory systems through innovative statistical modeling. The dynamics of these systems will be examined in association with child maltreatment and different forms of emerging psychopathology. The findings will augment the knowledge base regarding the sequelae of child maltreatment and the etiology of trauma-based psychopathology, and the knowledge gained will inform prevention and intervention initiatives to divert maltreated children from the development of trauma-related psychopathology and contribute toward reducing the burden of mental illness in traumatized children.

项目概要/摘要。 虐待儿童是对儿童施加的一种暴力形式，是一个复杂、阴险的问题， 尽管在贫困家庭中发生的情况更为常见，但这种情况贯穿社会的各个部门。的 虐待儿童的人类代价是一系列可能持续一生的生物和心理悲剧。 美国社会的经济成本是天文数字，数十亿美元花费在精神病，社会和文化方面。 服务，教育和司法系统成本，以及一代受虐待的生产力下降 孩子发现精神病理学和恢复力发展的潜在过程， 受虐待儿童为预防、干预和社会政策举措提供了很大的希望。 一个多层次的分析方法是不可或缺的理解不同的方式虐待儿童 危害健康在此，我们寻求利用大型数据集（N=1135），包括全面的 对受虐待儿童和人口统计学上可比的未受虐待儿童的评估。范围以外 原始NIH赠款，获得额外的生物学指标（基因型; DHEA和睾酮）， 有限的基础支持。简化这些生物措施并使用创新的定量方法 将使我们能够大大推进具有重大公共卫生意义的新知识。 现存的与虐待儿童有关的遗传学研究主要是在研究 基因与环境的相互作用（GxE），侧重于单基因多态性。鉴于各种形式的 与虐待相关的精神病理学，我们认为存在多种多基因风险复合物， 与虐待相互作用，影响儿童的结果。我们打算使用以人为本的方法来区分 个体共享参与应激反应系统的多个共同遗传多态性，并且 促进我们对儿童虐待中复杂的多基因x环境相互作用的理解。 我们还计划调查儿童虐待经历对应激反应的影响 激素系统，特别是下丘脑垂体肾上腺（HPA）和下丘脑垂体 性腺（HPG）轴。虽然HPA轴在影响方面受到了相当大的关注， 儿童虐待，关注HPG轴的作用以及这些轴之间的相互调节， 被限制。我们寻求通过创新的方法来扩大对这些调节系统功能障碍的理解。 统计建模这些系统的动态将与虐待儿童问题一起加以研究 和不同形式的新兴精神病理学 调查结果将增加有关虐待儿童后遗症的知识基础， 基于创伤的精神病理学的病因学，以及所获得的知识将为预防和干预提供信息 采取主动行动，使受虐待的儿童避免发展与创伤有关的精神病理学， 减少精神创伤儿童的精神疾病负担。