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

童年大规模创伤暴露、炎症性编程和青年期的精神病理学

• 批准号: 10611859
• 负责人: Lawrence Amsel
• 金额: $ 75.34万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10611859
• 关键词: Acute; Address; Adolescence; Adolescent; Adult; Affect; Age; Alzheimer' s Disease; Anti-Inflammatory Agents; Antigen-Antibody Complex; Applications Grants; Area; Asthma; Biological; Blood; Blood Pressure; Body mass index; Brain; Brain-Derived Neurotrophic Factor; Cardiovascular system; Child; Child Mental Health; Childhood; Clinical Research; Collaborations; Control Groups; Data; Development; Early identification; Epidemiology; Ethnic Origin; Event; Exhalation; Exposure to; Follow-Up Studies; Funding; Gender; Growth Factor; Health; Immune; Immune Plasma; Immune system; Immunologics; Immunology; Individual; Inflammation; Inflammatory; Inflammatory Response; Intervention; Link; Literature; Longitudinal Studies; Longitudinal cohort; Lung; Malignant Neoplasms; Measures; Mediating; Mental Health; Mental disorders; Metabolic syndrome; Methodology; Methods; Molecular; Morbidity - disease rate; Neuroimmune; Nitric Oxide; Oscillometry; Outcome; Pathway interactions; Personal Satisfaction; Physicians; Play; Prevention; Process; Psychiatrist; Psychiatry; Psychopathology; Pulmonary function tests; Pulmonology; Questionnaires; Relative Risks; Research; Risk; Risk Factors; Role; Science; Scientist; Shapes; Socioeconomic Status; Stress; Structure; System; Time; Translational Research; Trauma; Walking; adverse childhood events; arm; biobank; chemokine; childhood adversity; cohort; comorbidity; cost effective; cytokine; design; exposure pathway; gastrointestinal; immunoregulation; long-term sequelae; mortality; neuropsychiatry; pediatric trauma; pediatrician; physical conditioning; prevent; programs; psychiatric comorbidity; response; trauma exposure; young adult

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.

越来越多的文献表明，暴露于童年逆境和创伤（CAT） 显著增加终身身体疾病的风险，包括：肺，心血管和 胃肠道疾病、代谢综合征、某些癌症、阿尔茨海默病、精神疾病，以及， 尤其是身体和精神的共病此外，CAT暴露非常常见，因此 可能与相当大比例的成人合并症和死亡率相关。好在有 新出现的文献指出，免疫/炎症系统的重编程可能与 CAT和负面的身体和/或精神后遗症。虽然生物学途径还不完善 理解，更好地描述这些关系可以指出干预措施，以帮助早期 识别、预防和治疗接触过CAT的人。必要的研究受到阻碍 由于难以找到和评估足够大的队列， 暴露和纵向评估，以确定长期后遗症的客观证据。解决这些 挑战，这项建议借鉴了纵向队列，压力与幸福感（S&W）研究及其后续行动 研究，S&W2.这是最大的（N= 1，500），最全面的儿童身心健康研究 共同经历了创伤也就是911事件S&W2资助结构允许收集和生物银行 血，但需要一个单独的建议，其分析，从而使拟议的童年质量 创伤暴露，炎症编程和青年期的精神病理学（也称为 炎症与儿童期逆境和创伤[I-CATs]）研究非常具有成本效益。 根据S&W和S & W2两波的数据，特别是来自S & W2的生物库血液， 该提案旨在描述接触CAT与随后的 炎症/免疫特征，以及这些特征与长期合并症的关系。我们 多样的免疫分析组包括60种细胞因子、趋化因子和生长因子，其被选择为广泛地 代表促炎、抗炎/反调节、Th 17和T调节（Treg）臂 以及神经免疫分子，如BDNF和BDNF。总之，I-CAT 研究将：1）确定共同的集体创伤暴露与炎症特征的关系; 2） 表征那些免疫/炎症特征对身体的作用（可能是介导作用）， 精神和共病的结果在年轻人;和，3）最终，确定方法， 免疫/炎症结构域可能对暴露于CAT的患者的早期预防和治疗产生影响。