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。唾液蛋白质组的成分已知表现出对应激源的神经生物学反应，它们的生物计量潜力可以被利用来改变目前与应激相关的心理健康障碍相关的研究和临床实践范式。创伤应激障碍的重大问题为利用唾液应激生物标记物的差异表达提供了一个引人注目的翻译背景，以促进对应激反应的客观表征，并提供对应激相关精神病理学的复原力和脆弱性的见解。通过将基于“领域知识”的唾液生物标志物模式的时间变化与极端应激源的心理效应联系起来，我们将验证唾液生物标志物对 不适应的应激反应，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，推测的唾液应激生物标志物组合的表达水平将显示出不良适应应激反应，并预测创伤后精神病理学的发展。使用前瞻性样本收集、回顾盲法评估(探查)设计标准，在600名具有创伤(伤害或强奸)指数的患者(训练组=450，验证组=150)中，通过重复心理评估和多项唾液分析，我们将(1)验证已报道的个体唾液应激生物标记物与创伤后精神病理学(PTSD/MDD)之间的关联，(2)建立单个生物标记物的预测模型，并将其与创伤后精神病理学(PTSD/MDD)相关联；(3)确定创伤后精神病理学(PTSD/MDD)预测模型的性能特征；(4)探讨唾液应激生物标记物在创伤后精神病理学(PTSD/MDD)中的辅助诊断作用。我们的总体目标是开发护理点唾液生物传感器，以实现精神健康障碍创伤个人的筛查、监测和风险分层。通过这项研究，唾液“生物标记物标记”的发展提供创伤应激反应的信息，这是我们同时开发的新型、多路复合纳米传感器持续创新的重要组成部分。从长远来看，我们的跨学科研究战略，将唾液生物标记物面板和计算算法纳入行为评估，将在对创伤应激和精神病理学的理解、诊断和管理方面创造一种范式转变。

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.