Ambulatory Monitoring of Threat Dysregulation in Adolescents at Risk for Psychosis

对有精神病风险的青少年威胁失调的动态监测

• 批准号: 10616720
• 负责人: LESLIE E HORTON
• 金额: $ 60.09万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10616720
• 关键词: Acute; Adolescence; Adolescent; Affect; Affective; Age; Ambulatory Monitoring; Arousal; Autonomic nervous system; Award; Biological Process; Cardiac; Cardiovascular system; Cellular Phone; Chronic; Clinical; Clinical assessments; Cognitive; Congenital neurologic anomalies; Development; Diagnostic; Disease susceptibility; Early identification; Early treatment; Ecological momentary assessment; Emotional; Exhibits; Fright; Goals; Home; Hydrocortisone; Impairment; In Vitro; Individual; Intervention; Investigation; Laboratories; Life; Link; Literature; Measures; Mediating; Methods; Modeling; National Institute of Mental Health; Outcome; Participant; Pathway interactions; Patient Self-Report; Persons; Physiological; Prevention strategy; Procedures; Psychopathology; Psychophysiology; Psychoses; Psychotic Disorders; Recovery; Research; Research Domain Criteria; Rest; Risk; Role; Sampling; Schizophrenia; Sex Differences; Social Functioning; Social Processes; Stress; System; Technology; Testing; Theoretical model; Time; Visit; Youth; age difference; age group; aged; biological adaptation to stress; clinical high risk for psychosis; clinically relevant; comparison control; disability; experience; follow up assessment; high risk; hypothalamic-pituitary-adrenal axis; improved; in vivo; innovation; longitudinal design; mortality; multimodality; negative affect; novel; psychosis risk; psychotic symptoms; psychotic-like experiences; recruit; research clinical testing; response; sex; social; social relationships; stressor; wearable device

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.

项目摘要 拟议的研究旨在探讨生理威胁失调 (TD) 作为促成因素的作用 有精神病风险的青少年有社交障碍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节这种关系中发挥了作用。 尽管“素质-压力模型”是精神病和其他疾病发作的一个完善的框架。 尽管它是精神病理学的一种形式，但其应用于精神病的确切机制仍不清楚。这是一个重要的 机制来检查，因为 TD 会产生慢性恐惧和兴奋，这些状态会干扰社交 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空白 全面检查生理 TD，包括下丘脑-垂体-肾上腺的功能 (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， 检查 TD 与实验室和日常生活中的结果之间的联系。该提案将利用 纵向设计来研究 TD 与社交障碍的持续或恶化之间的关系 以及超过一年的类似精神病的经历。鉴于青春期后的青少年发展阶段是 精神障碍发展的敏感期，我们建议招募青春期后（14-17岁） 临床精神病高危青少年样本（CHR；n = 105）以及一组年龄和性别匹配的 对照（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） 稍后）在社会威胁诱导任务之前、期间和之后对 TD 进行临床评估和评估。 访问后将进行为期 2 周的家庭 EMA，以调查实时 ANS 威胁响应（通过心脏 可穿戴设备）、社交障碍、压力和类似精神病的经历（通过智能手机自我报告）。这 拟议的研究将是新颖的，因为它将 EMA 与尖端的动态心血管治疗相结合 心理生理学评估。因此，该提案将统一已建立的体外（实验室）评估 具有新颖的体内（EMA）评估的关键变量，后者具有较高的生态和临床价值 有效性。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 （国家精神卫生研究所）；特别是策略 2 和 3。所提出的概念模型与 NIMH 高度相关 持续和急性威胁系统的研究领域标准（RDoC）领域，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。拟议的奖项应该 1) 为 TD 理论模型的研究提供精确度，并且 它对社交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 针对有精神病风险的青少年的预防和干预策略。