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REM Sleep, Safety Signal Learning, and Extinction Processes in PTSD

快速眼动睡眠、安全信号学习和 PTSD 中的消退过程

基本信息

批准号：
8978685
负责人：
Laura D Straus
金额：
$ 3.53万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-01 至 2016-06-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Approximately 5.2 million adults suffer from posttraumatic stress disorder (PTSD) in a given year. PTSD is associated with a number of negative physical and mental health consequences. While evidence-based pharmacological and psychosocial interventions for PTSD have been developed within the last few decades, not all patients respond fully to treatment. Investigating the biological processes involved in the development and maintenance of PTSD as well as the mechanisms of treatment response will increase understanding of the disorder and aid in the development of effective interventions. Fear conditioning plays a crucial mechanistic role in PTSD, as patients with PTSD retain conditioned fear to cues associated with trauma long after the traumatic event has passed. Additionally, emerging evidence implicates deficits in safety learning in PTSD, as patients with PTSD are often unable to distinguish dangerous from safe environments. Extinction of conditioned fear is necessary for PTSD symptom reduction, either through the natural course of recovery or in response to exposure-based therapies for PTSD. In addition, it is crucial for patients to retain extinction over time as well as generalize extinction to a variety of settings ad cues in order to remain free of PTSD symptoms long-term. Our research group recently demonstrated an association between safety learning and Rapid Eye Movement (REM) sleep in healthy humans. The implications of this finding are particularly salient for patients with PTSD, because some of the most ubiquitous and distressing symptoms of PTSD are nightmares, which occur in REM sleep, and insomnia. Additionally, a growing body of research shows that sleep, particularly REM sleep, serves an important role in the acquisition, recall, and generalization of extinction memories in animal models and healthy humans. Nothing is known about the link between REM sleep and safety signal learning or extinction memory in clinical populations, though. This study will be the first to examine the relationship between safety signal learning, REM sleep, and extinction recall and generalization in PTSD patients. The specific aims of the proposal are: 1) determine if safety signal learning is related to subsequent REM sleep in patients with PTSD, and 2) determine if REM fragmentation is related to impaired a) extinction memory formation and b) extinction generalization, in patients with PTSD.

描述（由申请人提供）：在给定的一年中，大约有520万成年人患有创伤后应激障碍（PTSD）。PTSD与许多负面的身体和心理健康后果有关。虽然在过去的几十年里，已经开发了基于证据的PTSD药理学和心理社会干预措施，但并非所有患者都对治疗有完全反应。调查参与PTSD发展和维持的生物学过程以及治疗反应的机制将增加对这种疾病的理解，并有助于制定有效的干预措施。恐惧条件反射在创伤后应激障碍中起着至关重要的机制作用，因为创伤后应激障碍患者在创伤事件过去很长时间后仍保留对与创伤相关的线索的条件性恐惧。此外，新出现的证据表明创伤后应激障碍患者在安全学习方面存在缺陷，因为创伤后应激障碍患者通常无法区分危险环境和安全环境。条件性恐惧的消除对于PTSD症状的减轻是必要的，无论是通过恢复的自然过程还是对PTSD的基于焦虑的治疗的反应。此外，对于患者来说，随着时间的推移保持消退以及将消退推广到各种环境和线索以保持长期无PTSD症状是至关重要的。我们的研究小组最近证明了安全学习和健康人快速眼动（REM）睡眠之间的联系。这一发现对创伤后应激障碍患者的影响尤其突出，因为创伤后应激障碍的一些最普遍和最令人痛苦的症状是噩梦，这发生在快速眼动睡眠和失眠中。此外，越来越多的研究表明，睡眠，特别是REM睡眠，在动物模型和健康人的灭绝记忆的获得，回忆和概括中起着重要作用。然而，在临床人群中，关于REM睡眠与安全信号学习或消退记忆之间的联系还一无所知。这项研究将是第一个检查安全信号学习，REM睡眠，和灭绝回忆和概括的PTSD患者之间的关系。该提案的具体目的是：1）确定安全信号学习是否与PTSD患者随后的REM睡眠相关，以及2）确定REM碎片是否与PTSD患者受损的a）消退记忆形成和B）消退泛化相关。