Childhood Mass Trauma Exposure, Inflammatory Programming, and Psychopathology in Young Adulthood

越来越多的文献表明，接触童年的逆境和创伤(猫) 显著增加终生身体疾病的风险，包括：肺、心血管和 胃肠道疾病，代谢综合征，一些癌症，阿尔茨海默氏症，精神障碍，以及， 尤其是生理和精神并存。此外，接触猫是相当常见的，因此 可能与相当大比例的成人合并症和死亡率有关。幸运的是，有 新出现的文献指出免疫/炎症系统的重新编程可能是 猫和身体和/或精神上的负面后遗症。虽然生物途径还不是很好 理解，更好地描述这些关系可以指向早期干预以帮助 猫接触者的识别、预防和治疗。必要的研究受到了阻碍。 很难找到和评估足够大的、与定义明确的相关的队列 暴露和纵向评估，以确定长期后遗症的客观证据。要解决这些问题 挑战，这项建议借鉴了纵向队列，压力与幸福感(S和W)研究及其后续行动 研究，S和W2。这是规模最大(N=1500)、最全面的儿童身心健康研究 暴露在共同的创伤中，即9/11。S和W2的资金结构允许收集和生物银行 但有必要对其进行单独的分析，从而使拟议的儿童弥撒 创伤暴露、炎症性规划和青年时期的精神病理学(也称为 炎症与童年逆境和创伤[I-CATS])研究非常划算。 根据S&W和S&W2两次浪潮的数据，特别是S&W2的生物库血液，这一次 该提案旨在描述接触猫和随后的疾病概况之间的关系 炎症/免疫特征，以及这些特征与长期共病的关系。我们的 不同的免疫分析小组包括60种细胞因子、趋化因子和生长因子 代表促炎、抗炎/反调节、Th17和T调节(Treg)武器 免疫系统以及神经免疫分子，如脑源性神经营养因子和神经生长因子。总而言之，i-Cats 研究将：1)确定共同的大规模创伤暴露与炎症征兆的关系；2) 描述这些免疫/炎症信号对身体的作用(可能是中介作用)， 年轻人的精神和共病结果；以及，3)最终，确定从 免疫/炎症领域可能涉及到对接触猫的人的早期预防和治疗。

A growing body of literature indicates that exposure to childhood adversities and trauma (CATs) significantly increases the risk of lifelong physical morbidity, including: pulmonary, cardiovascular, and gastrointestinal conditions, metabolic syndrome, some cancers, Alzheimer’s disease, psychiatric disorders, and, especially, physical-psychiatric comorbidities. Moreover, CATs exposures are quite common and are therefore potentially associated with a significant proportion of adult comorbidities and mortality. Fortunately, there is emerging literature that points to reprogramming of the immune/inflammatory system as a possible link between CATs and negative physical and/or psychiatric sequelae. While the biological pathways are not yet well understood, a better characterization of these relationships could point to interventions to aid in early identification, prevention and treatment of those exposed to CATs. The necessary research has been hampered by the difficulty of finding and assessing cohorts that are sufficiently large, associated with well-defined exposures and assessed longitudinally to ascertain objective evidence of long-term sequelae. To address these challenges, this proposal draws on a longitudinal cohort, the Stress & Well-Being (S&W) Study and its follow up study, S&W2. This is the largest (N= 1,500), most comprehensive physical and mental health study of children exposed to a shared trauma, namely, 9/11. The S&W2 funding structure allowed for collecting and bio-banking of blood but necessitated a separate proposal for its analysis, thus making the proposed Childhood Mass Trauma Exposure, Inflammatory Programming, and Psychopathology in Young Adulthood (also called Inflammation and Childhood Adversity and Trauma [I-CATs]) Study very cost-effective. Drawing on data from the two waves of S&W and S&W2, notably bio-banked blood from S&W2, this proposal is designed to characterize the relationship between exposure to CATs and subsequent profiles of inflammatory/immune signatures, and the relationship of those signatures to long-term comorbidities. Our diverse immune profiling panel includes 60 cytokines, chemokines and growth factors selected as being broadly representative of the proinflammatory, anti-inflammatory/counter-regulatory, Th17 and T regulatory (Treg) arms of the immune system, as well as neuroimmune molecules, such as BDNF and NGF. In summary, the I-CATs Study will: 1) identify the relationship of a shared mass trauma exposure to inflammatory signatures; 2) characterize the role (possibly a mediating role) that those immune/inflammatory signatures have on physical, psychiatric and comorbid outcomes in young adults; and, 3) ultimately, identify approaches from the immune/inflammatory domain to potentially bear on early prevention and treatment of those exposed to CATs.