Salivary Biomarker Panel for Measuring and Predicting Traumatic Stress Reactions

描述（由申请人提供）：评估一般压力，特别是创伤压力的最重要挑战之一是过度依赖患者自我报告和临床行为观察。唾液蛋白质组的组成部分是已知的，以体现神经生物学反应的压力和他们的生物测定的潜力，可以被利用来改变目前的研究和临床实践范式与压力相关的心理健康障碍。创伤性应激障碍的重大问题提供了一个引人注目的翻译背景，利用推定的唾液应激生物标志物的差异表达，以促进客观表征的应激反应，并提供洞察力和脆弱性的压力相关的精神病理学。通过将基于“领域知识”的唾液生物标志物模式中的时间变化与极端应激的心理效应相关联，我们将验证唾液生物标志物对应激的区分和预测效用。 适应不良的应激反应，如创伤后应激障碍（PTSD）和重度抑郁发作（MDD）。我们假设，在创伤患者的高危人群中，推定的唾液应激生物标志物的组合的表达水平将表现出适应不良的应激反应，并预测创伤后精神病理学的发展。在600例患者队列中使用前瞻性标本采集、回顾性设盲评价（探针）设计标准（训练集= 450，验证集= 150）通过反复的心理评估和多路唾液分析，我们将（1）验证个体唾液应激生物标志物与创伤后精神病理学之间的相关性（2）建立一个结合个体生物标志物并将其与创伤后精神病理学（PTSD/MDD）相关联的预测模型（3）确定创伤后精神病理学（PTSD/MDD）预测模型的性能特征（4）探索唾液应激生物标志物在创伤后精神病理学（PTSD/MDD）中的连续诊断效用。 我们的总体目标是开发即时护理，唾液生物传感器，以操作精神健康障碍的创伤个体的筛查，监测和风险分层。通过这项研究开发的唾液“生物标志物签名”提供创伤应激反应的信息，是我们正在同时开发的新型多路复用纳米传感器的持续创新的重要组成部分。从长远来看，我们希望我们的跨学科研究策略，将唾液生物标志物面板和计算算法纳入行为评估，将在创伤应激和精神病理学的理解，诊断和管理方面创造一个范式转变。 公共卫生相关性：极端压力在许多方面影响心理健康。目前对主观自我报告和临床行为观察的依赖往往导致新出现的心理健康问题被错过，直到他们成为既定的，难以治疗。我们计划使用压力标记蛋白，目前在唾液中检测未来的心理健康问题在早期阶段，当他们更响应于治疗。

DESCRIPTION (provided by applicant): One of the most important challenges of assessing stress in general, and traumatic stress in particular, is the undue reliance on patient self-report and clinical behavioral observations. Components of the salivary proteome are known to manifest the neurobiological response to stressors and their biometric potential could be exploited to transform current research and clinical practice paradigms related to stress-related mental health disorders. The significant problem of traumatic stress disorders provides a compelling translational context for utilizing the differential expression of putative salivary strss biomarkers to facilitate objective characterization of the stress response and provide insights into resilience and vulnerability to stress related psychopathology. By relating temporal changes in "domain-knowledge" based salivary biomarker patterns to the psychological effects of an extreme stressor, we will verify the discriminate and predictive utility of salivary biomarkers for maladaptive stress reactions such as post-traumatic stress disorder (PTSD) and major depressive episode (MDD). We hypothesize that the expression levels of combinations of putative salivary stress biomarkers, in an at-risk population of trauma patients, will manifest maladaptive stress reactions and predict the development of post-trauma psychopathology. Using prospective-specimen-collection, retrospective-blinded-evaluation (Probe) design criteria in a cohort of 600 patients (training set = 450, validation set= 150) with an index trauma (injury or rape) and through repeat psychological assessments and multiplexed salivary assays, we will (1) Validate the reported associations between individual salivary stress biomarkers and post-trauma psychopathology (PTSD/MDD), (2) Develop a prediction model that combines the individual biomarkers and relates them to post-trauma psychopathology (PTSD/MDD) (3) Determine the performance characteristics of the prediction model of post-trauma psychopathology (PTSD/MDD) and (4) Explore the adjunctive diagnostic utility of salivary stress biomarkers in post-trauma psychopathology (PTSD/MDD). Our overarching goal is to develop point-of-care, salivary biosensors to operationalize the screening, monitoring and risk stratification of traumatized individuals for mental health disorders. The development of salivary "biomarker signatures" informative of traumatic stress responses through this study is an essential building block for the continued innovation of novel, multiplexed nanosensors that we are developing concomitantly. In the long term, we expect that our interdisciplinary research strategy, incorporating salivary biomarker panels and computational algorithms into behavioral assessments, will create a paradigm shift in the understanding, diagnosis and management of traumatic stress and psychopathology. PUBLIC HEALTH RELEVANCE: Extreme stress affects mental health in many ways. The current reliance on subjective self-reports and clinical behavioral observations often cause emerging mental health problems to be missed until they become established and difficult to treat. We plan to use stress-marker proteins that present in saliva for detecting future mental health problems at an early stage when they are more responsive to treatments.