Salivary Biomarker Panel for Measuring and Predicting Traumatic Stress Reactions

描述（由申请人提供）：评估一般压力，特别是创伤性压力最重要的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已知表现出对压力源的神经生物学反应，它们的生物识别潜力可以被利用来改变当前与压力相关的精神健康障碍相关的研究和临床实践范式。创伤性应激障碍的重大问题为利用假定的唾液应激生物标志物的差异表达来促进应激反应的客观表征，并提供对应激相关精神病理的恢复力和脆弱性的见解提供了令人信服的翻译背景。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压力源的心理影响联系起来，我们将验证唾液生物标志物对抑郁症的区分和预测效用

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.