Risk Profiles and Mechanisms of Disease in Maltreated Children

儿童期虐待是一个主要的公共卫生问题，与高比率的情绪和焦虑有关 疾病，并且越来越多的文献记载了诸如肥胖，心血管疾病， 哮喘和糖尿病。这些疾病通常是慢性和严重的，它们在治疗过程中需要付出巨大的代价。 痛苦，残疾，治疗和生产力损失。现有的社会服务计划， 受虐待的儿童缺乏关于哪些儿童有可能患上哪些精神疾病的数据， 结果和缺乏对其他不良健康状况风险的关注。为了开发更多 有针对性和具体的干预和治疗，我们需要更好地了解轨迹， 风险机制和保护因素。有证据表明逆境的病理生理影响 在生命的早期就开始开始，重大逆境的临床或亚临床影响可以在儿童时期看到。 受虐待的儿童，特别是生活贫困的儿童，患早发性疾病的风险特别高， 儿童虐待通常是秘密的，因此很难研究。这项研究为期5年， 对受虐待的贫困学龄前儿童样本进行后续评估， 匹配未受虐待的儿童。现有数据包括虐待经历、社会经济状况、 因素和邻里特征，以及其他逆境，如失去父母，无家可归， 创伤保护因素的数据包括家庭和邻里资源，养育和社会服务。 在我们最初的工作中，不良经历与抑郁症状和皮质醇水平降低有关， 糖皮质激素信号基因的表观遗传变化是这些关系的重要介质。我们也 发现唾液炎性细胞因子IL-1β的水平随着应激暴露而增加。在我们 在对健康的未用药成年人的研究中，我们发现， 与代谢综合征的几个指标有关，儿童期的压力和精神状况 与端粒缩短和线粒体DNA增殖有关，细胞凋亡的指标 压力和衰老。在拟议的5年随访中，我们将测试一个风险和弹性模型， 从病历、访谈和儿童完成的问卷中获得的精神病学结果 以及认知/情感、代谢、血管内和肺功能的测试。行为上， 将研究风险和复原力的社会和生物机制。统计模型将针对 确定最可能有用的风险和保护因素以及生物机制的概况 干预的目标。

Childhood maltreatment is a major public health problem that is linked to high rates of mood and anxiety disorders, and a growing literature documents risk for conditions such as obesity, cardiovascular disease, asthma, and diabetes. These conditions are often chronic and severe, and they exact tremendous costs in terms of suffering, disability, treatment, and loss of productivity. Existing social services programs for maltreated children suffer from a lack of available data regarding which children are at risk for which psychiatric outcomes and from a lack of focus on risk for other adverse health conditions. In order to develop more targeted and specific interventions and treatments, we need to better understand the trajectory and mechanisms of risk and protective factors. There is evidence that the pathophysiological effects of adversity begin early in life, and that clinical or sub-clinical effects of major adversity can be seen in childhood. Maltreated children, particularly those living in poverty, are at especially high risk for early-onset disorders, but childhood maltreatment is usually clandestine and therefore very difficult to study. This study involves a 5-year follow up assessment of a sample of impoverished maltreated preschool-aged children and demographically matched non-maltreated children. Existing data include details of maltreatment experiences, socioeconomic factors and neighborhood characteristics, and additional adversities such as parental loss, homelessness, and traumas. Data on protective factors include home and neighborhood resources, parenting, and social services. In our initial work, adverse experiences were linked to depressive symptoms and blunted cortisol levels, and epigenetic changes to glucocorticoid signaling genes were significant mediators of these relationships. We also found that levels of salivary inflammatory cytokine IL-1β increased as a function of stress exposure. In our work with healthy un-medicated adults, we have shown that attenuated plasma cortisol concentrations are linked to several indices of the metabolic syndrome, and that childhood stress and psychiatric conditions are associated with telomere shortening and a measure of mitochondrial DNA proliferation, indicators of cellular stress and aging. In the proposed 5-year follow-up, we will test a model of risk and resilience for medical and psychiatric outcomes obtained from medical records, from interviews and questionnaires completed by children and caregivers, and tests of cognitive/affective, metabolic, endovascular, and pulmonary function. Behavioral, social, and biological mechanisms of risk and resilience will be examined. Statistical models will be aimed at identifying profiles of risk and protective factors and biological mechanisms that are most likely to be useful targets for intervention.