Ambulatory Monitoring of Threat Dysregulation in Adolescents at Risk for Psychosis

项目摘要 这项拟议的研究试图检验生理威胁失调(TD)作为促成因素的作用。 精神病高危青少年的社会损害和类似精神病的经历，并进一步检查其程度 错误的认知和情感威胁反应在部分调解这种关系中起到了作用。 尽管“素质-压力模型”是精神病和其他疾病发病的良好框架。 作为精神病理学的一种形式，其适用于精神病的确切机制尚不清楚。这是一个重要的 检查机制，因为TD可以产生慢性恐惧和唤醒，干扰社会的状态 人际关系和健康发展。拟议的研究将通过以下方式解决文献中的这一差距 全面检查生理性TD，包括下丘脑-垂体-肾上腺功能 (HPA)轴和自主神经系统(ANS)。目前的提案使用了多种方法，包括 实验室评估、生态瞬时评估(EMA)和动态心理生理学，以 检查TD与实验室和日常生活中的结果之间的联系。这项提案将利用 纵向设计，研究TD与社会损害的持续或恶化之间的关系 有1年以上的精神病史。鉴于青春期后青春期发育阶段是 精神障碍发展的敏感期，我们建议招募一名青春期后(14-17岁) 临床精神疾病高危青少年样本(CHR；n=105)和年龄和性别匹配的一组 对照组(n=70)。多方法评估将包括3次实验室访问(基线、6个月和1年 随后)在社会威胁诱导任务之前、期间和之后进行临床评估和TD评估。 会诊后将进行为期两周的居家急救，以调查实时ANS威胁反应(通过心脏 可穿戴设备)、社交障碍、压力和类似精神病的体验(通过智能手机自我报告)。这个 拟议的研究将是新颖的，因为它将把EMA与尖端的、动态的心血管疾病配对 心理生理学评估。因此，这项建议将统一已建立的体外(实验室)评估 关键变量与新的体内(EMA)评估，后者具有很高的生态和临床价值 有效性。该项目的目标与国家精神卫生研究所的战略目标非常匹配 (NIMH)；特别是策略2和3。拟议的概念模型与NIMH高度相关 持续和严重威胁系统的研究领域标准(RDoC)领域，以及 因此，这项研究应该对跨诊断的精神病理学的研究具有相关性 边界。拟议的奖励应1)为TD的理论模型的研究提供精确度，以及 它对社会损害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，以及3)提出新的改善方向。 青少年精神病高危人群的预防和干预策略。

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.