Childhood Maltreatment and Disease Risk in Young Adulthood: The Role of HPA Regulation in Adolescence

童年虐待和青年期疾病风险：HPA 调节在青春期的作用

• 批准号: 10446121
• 负责人: Sonya L Negriff
• 金额: $ 69.75万
• 依托单位: KAISER FOUNDATION RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10446121
• 关键词: Address; Adolescence; Adolescent Development; Adult; Biological; Biological Aging; Biological Markers; Body mass index; C-reactive protein; Cardiovascular Diseases; Caregivers; Cells; Child; Child Abuse; Child Abuse and Neglect; Childhood; Chronic; Chronic Disease; Clinical; Communities; Data; Data Set; Development; Disease; Early-life trauma; Economic Burden; Enrollment; Epigenetic Process; Ethnic Origin; Functional disorder; Future; Health; Immune; Individual; Individual Differences; Inflammatory; Interleukin-6; Intervention; Knowledge; Lead; Life; Link; Longitudinal Studies; Lung diseases; Malignant Neoplasms; Measures; Mediation; Mental Health; Metabolic syndrome; Minority; Modeling; Morbidity - disease rate; Outcome; Pathway interactions; Pattern; Physiological; Prevention; Process; Race; Recording of previous events; Regulation; Reporting; Risk; Risk Factors; Role; Self Perception; Severities; Shapes; Social support; Stress; Symptoms; System; TNF gene; Techniques; Testing; Time; Trauma; Vulnerable Populations; Well in self; Work; Youth; allostatic load; biological adaptation to stress; child neglect; comparison group; cost; disorder risk; early life stress; experience; follow up assessment; hypothalamic-pituitary-adrenal axis; improved; indexing; innovation; insight; longitudinal dataset; maltreatment; mortality; physical conditioning; prevent; prospective; protective factors; resilience; response; social; transmission process; young adult

Abstract Child maltreatment is a significant and costly social issue with over 670,000 documented cases annually. The effects of maltreatment are wide-ranging and include increased rates of morbidity and mortality from chronic diseases. To improve the health and mortality of this vulnerable population it is critical to delineate the pathways through which maltreatment contributes to increased risk for disease and identify opportunities for prevention. Dysregulation of the body’s physiological stress response systems constitutes a key pathway through which early maltreatment shapes biological aging processes and risk for subsequent disease. In addition, recalibration of the stress system during adolescence may mitigate the effects of early trauma on disease risk. Although the HPA axis in particular has been implicated as a key mechanism linking maltreatment with disease, these associations have only been tested between any two of these variables (i.e., maltreatment and HPA axis function, maltreatment and disease, or HPA axis function and disease) using cross-sectional or retrospective reports of maltreatment. This study will be the first to test this hypothesized mediation model from maltreatment to disease risk via HPA functioning using a developmental framework from childhood to young adulthood, incorporating multiple indices of disease risk. Second, the proposed work will be the first to use innovative new modeling techniques to characterize HPA axis functioning across four timepoints in adolescence to pinpoint the particular aspects of the stress response and developmental periods of stress system sensitivity that may lead to disease risk. Finally, this study will move beyond current conceptualizations of stress system dysfunction by identifying resilient profiles of HPA axis functioning and moderators of HPA axis recalibration that will provide critical new insights for intervention efforts focused on mitigating the effects of maltreatment on disease risk. The importance of assessing disease risk in young adulthood is bolstered by data indicating this period of life as a potential inflection point for long-term disease risk. As such, young adulthood may be a critical window for prevention and an optimal time to assess modifiable health risks. To accomplish this, we will leverage a unique prospective longitudinal dataset including youth with documented maltreatment histories and a comparison group from the same communities (90% minority race/ethnicity). This exemplary dataset will be augmented with follow-up assessment in young adulthood to capture disease risk. The findings will provide the first longitudinal evidence of HPA axis as a critical mechanism through which childhood maltreatment contributes to a lifelong trajectory of disease and whether recalibration of the HPA axis in adolescence can mitigate the effects of early trauma on disease risk in young adulthood. Identification of specific moderators of HPA axis recalibration can directly inform intervention and prevent stress-induced disease.

摘要 虐待儿童是一个重大和代价高昂的社会问题，每年有超过670 000起记录在案的案件。的 虐待的影响是广泛的，包括慢性疾病的发病率和死亡率增加， 疾病为了改善这一弱势群体的健康和死亡率， 虐待导致疾病风险增加的途径，并确定 预防人体生理应激反应系统的失调构成了 早期的虐待通过这种方式塑造了生物衰老过程和随后疾病的风险。在 此外，在青春期重新调整压力系统可能会减轻早期创伤的影响， 疾病风险。虽然HPA轴特别被认为是连接虐待的关键机制， 对于疾病，仅在这些变量中的任何两个之间测试了这些关联（即，虐待 和HPA轴功能，虐待和疾病，或HPA轴功能和疾病）使用横断面或 虐待的回顾性报告。这项研究将是第一个测试这个假设的调解模式， 通过HPA功能使用从童年到年轻的发展框架， 成年期，包括多种疾病风险指数。二是拟开展的工作将率先使用 创新的新建模技术，以表征HPA轴在四个时间点的功能， 青少年时期，以确定压力反应的特定方面和压力的发展时期 可能导致疾病风险的系统敏感性。最后，这项研究将超越当前的概念化 通过识别HPA轴功能的弹性特征和HPA调节剂， 轴的重新校准，将为重点减轻影响的干预工作提供重要的新见解 虐待的风险。评估青年期疾病风险的重要性得到了以下方面的支持： 数据表明，这段生命时期是长期疾病风险的潜在拐点。因此，年轻 成年期可能是预防的一个关键窗口，也是评估可改变的健康风险的最佳时机。到 为了实现这一目标，我们将利用一个独特的前瞻性纵向数据集，包括记录在案的青年 虐待历史和来自同一社区的比较组（90%是少数族裔）。这 示范性数据集将通过青年期的随访评估来增强，以捕获疾病风险。 这些发现将提供HPA轴作为一个关键机制的第一个纵向证据， 儿童期的虐待会导致终生的疾病轨迹， 可以减轻早期创伤对青年期疾病风险的影响。鉴定 HPA轴重新校准的特定调节者可以直接告知干预， 疾病