Genes, Behavior, and Psychosocial Links of Child Maltreatment to Health, Disease

描述（由申请人提供）：一个儿童压力源——儿童虐待——代表了一个严重的公共卫生问题。2007年，美国有300多万儿童因涉嫌虐待而被转介到儿童保护服务机构，其中约79.4万儿童被州和地方儿童保护服务机构认定为虐待受害者（DHHS, 2009）。越来越多的证据表明，儿童时期的身体虐待和性虐待以及（最近的）忽视在多个领域具有广泛的短期和长期后果，包括精神、社会、情感、行为、学术、身体功能和发育时间点。相关的社会成本估计每年达数十亿美元。与此同时，童年受害的负面后遗症并非不可避免。虽然对这些不同结果的解释仍然未知，但研究已经开始研究可能缓冲或保护受虐待儿童免受负面影响的因素。最近的研究报告了儿童虐待和遗传变异在预测心理和行为结果（包括暴力和反社会行为、抑郁、焦虑、自杀、酗酒和药物使用）方面的显著相互作用。拟议研究的首要目标是测试虐待和忽视儿童导致成年后身心健康后果的三个相互竞争的过程模型。这里提出的研究代表了1986年开始的纵向研究的延续，该研究包括一大批记录的儿童身体和性虐待和忽视的案例（0-11岁），以及一组未受虐待和未被忽视的儿童，这些儿童根据年龄、性别、种族/民族和大致的家庭社会阶层进行匹配，并通过四次访谈随访到成年。我们建议使用在前几轮研究中已经收集到的血液和唾液样本。我们的目标是识别、分型和分析基因变异，并确定它们是否在儿童虐待和忽视的长期身心健康后果中发挥作用。拟议的研究将增进对童年压力经历（如儿童忽视和虐待）导致不同身心健康结果发展的多种途径的理解，并与奥巴马总统对卫生保健教育和预防负面健康结果的强调保持一致。确定遗传和环境因素之间的相互作用，这些因素增加了受虐待和被忽视儿童的负面身心健康结果的风险，或促进了他们的恢复能力，这对这些儿童的治疗和预防工作具有重要意义。通过确定特定的环境（如虐待或忽视的家庭）是否对具有特定基因的儿童特别有问题，我们希望拟议的研究将为集中干预提供方向。

DESCRIPTION (provided by applicant): One childhood stressor - child maltreatment - represents a serious public health concern. In 2007, over 3 million children were referred to child protection service agencies for suspected maltreatment in the United States and about 794,000 were determined by state and local child protective service agencies to be victims of maltreatment (DHHS, 2009). Increasing evidence shows that childhood physical and sexual abuse and (more recently) neglect have extensive short- and long-term consequences across multiple domains, including psychiatric, social, emotional, behavioral, academic, and physical functioning, and developmental time points. The associated costs to society have been estimated at billions of dollars annually. At the same time, the negative sequelae of childhood victimization are not inevitable. While explanations for these different outcomes remain unknown, research has begun to examine factors that might buffer or protect maltreated children from negative consequences. Recent research has reported significant interactions between childhood maltreatment and genetic variation in predicting psychological and behavioral outcomes, including violence and antisocial behavior, depression, anxiety, suicidality, alcoholism, and substance use. The overarching goal of the proposed research is to test three competing models of the processes whereby child abuse and neglect lead to mental and physical health consequences in adulthood. The research proposed here represents a continuation of a longitudinal study begun in 1986 with a large group of documented cases of childhood physical and sexual abuse and neglect (ages 0-11) and a comparison group of non-abused and non-neglected children who were matched on the basis of age, sex, race/ethnicity, and approximate family social class and followed up into adulthood with four interviews. We propose to use blood and saliva samples that have already been collected as part of previous waves of the study. Our goal is to identify, genotype, and analyze genetic variants and to determine whether they play a role in the long-term physical and mental health consequences of child abuse and neglect. The proposed research will lead to increased understanding of the multiple pathways through which stressful childhood experiences (such as child neglect and abuse) lead to the development of different mental and physical health outcomes and is in keeping with President Obama's emphasis on health care education and the prevention of negative health outcomes. Determining the interplay between genetic and environmental factors that increase risk for negative physical and mental health outcomes or promote resiliency among abused and neglected children has implications for treatment and prevention efforts for these children. By determining whether a particular environment (such as an abusive or neglectful home) is particularly problematic for children with certain genes, we hope that the proposed research will provide directions for focused interventions. PUBLIC HEALTH RELEVANCE: Child maltreatment, one major source of childhood stress, is a serious public health problem, with about 800,000 substantiated cases of childhood victimization each year. Recent research has reported significant interactions between child maltreatment and genetic variations in predicting psychological and behavioral outcomes. The overarching goal of the proposed research is to test three models that have been proposed to understand the linkages between childhood maltreatment and long-term physical and mental health consequences and, ultimately, may lead to the development of appropriate intervention strategies.