Ambulatory Monitoring of Threat Dysregulation in Adolescents at Risk for Psychosis

项目摘要 这项拟议的研究旨在研究生理威胁失调（TD）作为一个贡献者的作用， 社会障碍和精神病样的经验，在青年精神病的风险，并进一步检查的程度， 错误的认知和情感威胁反应在部分调解这种关系中发挥作用。 虽然“素质-压力模型”是精神病和其他精神疾病发病的一个完善的框架， 虽然精神病理学的形式不同，但其适用于精神病的确切机制仍不清楚。这是一个重要 检查机制，因为TD可以产生慢性恐惧和唤醒，这些状态会干扰社会 关系和健康发展。拟议的研究将通过以下方式填补文献中的这一空白： 全面检查生理TD，包括下丘脑-肾上腺-肾上腺的功能 (HPA)自主神经系统（Autonomic Nervous System，ANS）目前的提案使用多种方法，包括 实验室评估、生态瞬时评估（EMA）和动态心理生理学， 检查TD和实验室和日常生活中的结果之间的联系。该提案将利用 纵向设计，以检查TD如何与社会障碍的持续或恶化相关 和精神病经历超过一年。鉴于青春期后的青少年发展阶段是一个 精神障碍发展的敏感期，我们建议招募青春期后（14-17岁） 精神病临床高危青少年样本（105例）和一组年龄和性别匹配的 对照组（n = 70）。多方法评估将包括3次实验室访视（基线、6个月和1年 随后）在社会威胁诱导任务之前、期间和之后对TD进行临床评估和评价。 访视后将进行2周的在家EMA，以调查实时ANS威胁反应（通过心脏 可穿戴设备），社交障碍，压力和精神病样体验（通过智能手机自我报告）。的 拟议的研究将是新颖的，因为它将EMA与尖端的非卧床心血管 心理生理学评估因此，该提案将联合已建立的体外（实验室）评估， 新的体内（EMA）评估的关键变量，后者具有较高的生态和临床价值 效度该项目的目标与国家心理健康研究所的战略目标非常吻合 （NIMH）;特别是战略2和3。所提出的概念模型与NIMH高度相关 研究领域标准（RDoC）领域的持续和急性威胁系统，以及“社会” 过程”领域;因此，这项研究应该与跨诊断的精神病理学研究相关。 边界拟议的裁决应：1）为TD理论模型的调查提供精确性， 它对社会障碍和精神病样经历的影响，2）有助于EMA的发展- 基于“早期预警系统”来预测精神病的变化，3）提出改进的新方向 为有精神病风险的青少年制定预防和干预战略。

PROJECT ABSTRACT The proposed study seeks to examine the role of physiological threat dysregulation (TD) as a contributor to social impairment and psychotic-like experiences in youth at-risk for psychosis, and further examine the extent to which faulty cognitive and affective threat responses play a role in partially mediating this relationship. Although the “diathesis-stress model” is a well-established framework for the onset of psychosis and other forms of psychopathology, the exact mechanism as it applies to psychosis remains unclear. This is an important mechanism to examine because TD can generate chronic fear and arousal, states which interfere with social relationships and healthy development. The proposed study will address this gap in the literature by comprehensively examining physiological TD, including the function of the Hypothalamic-Pituitary-Adrenal (HPA) axis and the Autonomic Nervous System (ANS). The current proposal uses multiple methods, including laboratory assessments, ecological momentary assessment (EMA), and ambulatory psychophysiology, to examine the link between TD and outcomes in the laboratory and in daily life. This proposal will utilize a longitudinal design to examine how TD is associated with the persistence or worsening of social impairment and psychotic-like experiences over 1 year. Given that the post-pubertal adolescent developmental stage is a sensitive period for the development of psychotic disorders, we propose to recruit a post-pubertal (age 14-17) sample of adolescents at clinical high-risk for psychosis (CHR; n = 105) and a group of age- and sex-matched controls (n = 70). Multi-method assessments will include 3 laboratory visits (Baseline, 6 months, and 1 year later) with clinical assessments and evaluation of TD before, during, and after a social threat induction task. Visits will be followed by 2 weeks of at-home EMA to investigate real-time ANS threat response (via cardiac wearable device), social impairment, stress, and psychotic-like experiences (via smartphone self-report). The proposed study would be novel in that it will to pair EMA with cutting-edge, ambulatory cardiovascular psychophysiology assessment. Thus, this proposal would unite established in vitro (laboratory) assessments of key variables with novel in vivo (EMA) assessments, the latter of which have high ecological and clinical validity. The aims of the project match well with the strategic goals of the National Institute of Mental Health (NIMH); in particular, Strategies 2 and 3. The proposed conceptual model is highly relevant to the NIMH Research Domain Criteria (RDoC) domains of the sustained and acute threat systems, as well as the “social processes” domain; thus, this research should have relevance to the study of psychopathology across diagnostic boundaries. The proposed award should 1) provide precision to investigation of a theoretical model of TD and its impacts on social impairment and psychotic-like experiences, 2) contribute to the development of an EMA- based “early warning system” to predict changes in psychosis, and 3) suggest new directions for improved prevention and intervention strategies for adolescents at-risk for psychosis.