Differential impacts of co-occurring childhood maltreatment and long-term poly-victimization on chronic physical illnesses via inflammation: Do age at exposure and sexual orientation matter?

项目总结/摘要 了解12岁以前同时发生的儿童虐待和12岁以前同时发生的儿童虐待的不同影响 在18岁之前和成年之前，身体慢性疾病的多重受害者是至关重要的，因为他们 影响深远的公共卫生和经济后果，特别是对女同性恋、男同性恋、 和双性恋或LGB个体。同样重要的是识别免疫机制， 被受害激活并思考每种受害类型与慢性身体疾病之间的联系 疾病，以及暴露于每次受害发生的发展阶段。这样的 评估将扩大我们的知识，哪些共同发生的受害类型是最有影响的具体 慢性生物失调，让我们更好地了解受害的稳定性和可塑性 相关的生物失调。考虑到同性恋、双性恋和变性者在每种受害类型中都面临更大的风险， 与异性恋者相比，LGB的健康差异风险更大， 个体将经历更大的受害相关的生物失调， 慢性疾病的。同样，儿童时期（12岁之前）的受害暴露也通常 被认为对终身健康影响更大。因此，本项目的总体目标是解决 三个主要目标：（1）确定a）年龄之前同时发生的儿童期虐待 12，B）18岁之前共同发生的多重受害，以及c）成年之前共同发生的多重受害， 和慢性身体疾病。2)检测促炎细胞因子DNA甲基化的介导作用， CRP基因以及炎症的血清生物标志物（例如CRP、IL-6、TNF-α）作为在 每种受害类型和慢性身体疾病。3)了解是否以及如何（更强与更弱 共同发生的童年虐待和共同发生的多- 受害与成人健康有关，因性取向和发育阶段而异。 该F32还将允许候选人在其现有专业知识的基础上进行所需的时间和培训 成为一名独立的跨学科研究人员。通过与经验丰富的导师进行培训， 是该领域的领导者，候选人将获得1。在社会基因组学研究和新的统计 分析DNA甲基化数据的方法，2.行为免疫学和免疫学知识 身体健康，3。深入了解性少数群体的健康差异，如LGB 个人，4。整合社会、生物和发展领域的理论、数据和方法 研究领域和研究成果的翻译。在这些领域和研究道德方面的培训是 完成研究目标，并为候选人作为NIH资助的研究人员的职业生涯做好准备 调查性少数群体受害者的健康状况。

Project Summary/Abstract Understanding the differential effects of co-occurring childhood maltreatment prior to age 12 and co-occurring poly-victimization prior to age 18 and until young adulthood on physical chronic illnesses are critical due to their far-reaching public health and economic consequences, particularly for sexual minorities such as lesbian, gay, and bisexual or LGB individuals. Of equal importance is the identification of immune mechanisms that get activated by victimization and meditate the association between each victimization type and chronic physical illnesses, as well as the developmental stage during which exposure to each victimization occurs. Such an evaluation will expand our knowledge of which co-occurring victimization types are most influential for specific chronic biological dysregulation and give us a better understanding of the stability and plasticity of victimization related biological dysregulation. Given that LGB individuals are at a greater risk for each victimization type and at greater risk for health disparities, it is equally likely that compared to heterosexual individuals, LGB individuals will experience greater victimization related biological dysregulation and subsequently higher levels of chronic illnesses. Similarly, victimization exposures in childhood (before age 12) are also generally considered worse for lifelong health outcomes. Therefore, the overarching goal of this project is to address three primary aims: 1) establish the relationship between a) co-occurring childhood maltreatment prior to age 12, b) co-occurring poly-victimization until age 18, and c) co-occurring poly-victimization until young adulthood, and chronic physical illnesses. 2) Examine mediating role of DNA methylation of pro-inflammatory cytokine and CRP genes as well as serum biomarkers of inflammation (e.g. CRP, IL-6, TNF-α) as a mechanism between each victimization type, and chronic physical illnesses. 3) Understand whether and how (stronger vs. weaker associations) the biosocial processes by which co-occurring childhood maltreatment and co-occurring poly- victimization is related to adult health varies by sexual orientation and development stage. This F32 will also allow the Candidate the time and training required to build on her existing expertise required to become an independent and interdisciplinary researcher. Through training with experienced mentors who are leaders in the field, the Candidate will gain 1. expertise in social genomics research and novel statistical methods for analyzing DNA methylation data, 2. knowledge in behavioral immunology and immune mechanisms of physical health, 3. in-depth knowledge of sexual minority health disparities such as LGB individuals, and 4. integration of theory, data and methods across social, biological, and developmental domains and translation of research findings. Training in these areas and in research ethics is integral for completing the research aims, and preparing the Candidate for a career as a NIH-funded researcher investigating victimization related health outcomes among sexual minorities.