Straus Laura D, Norman Sonya B, Risbrough Victoria B, Acheson Dean T, Drummond Sean P A
Mental Illness Research Education and Clinical Centers, San Francisco VA Healthcare System, San Francisco, CA, USA.
Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA.
Neurobiol Stress. 2018 Jul 20;9:22-28. doi: 10.1016/j.ynstr.2018.07.001. eCollection 2018 Nov.
Posttraumatic Stress Disorder (PTSD) is associated with a number of negative physical and mental health consequences. Fear conditioning plays an important mechanistic role in PTSD, and PTSD patients also show deficits in safety signal learning. Sleep, particularly REM sleep, is linked to improved safety learning and extinction processes in animal models and healthy humans. No studies have examined the link between REM sleep and safety signal learning or extinction memory in clinical populations.
This study examined the relationship between REM sleep, safety signal learning, and extinction processes in veterans with PTSD ( = 13). Patients' overnight sleep was characterized in the laboratory via polysomnography (PSG). The next day, participants underwent a fear conditioning paradigm during which they acquired fear toward a visual cue. This testing session also included a visual cue that became a safety signal (CS-). Following conditioning, the veterans' sleep was monitored overnight again, after which they underwent extinction training. Following a third night of sleep, extinction recall and safety recall were tested. Bivariate correlations examined the relationship between the slope of safety signal learning and subsequent REM sleep, as well as the relationship between REM sleep and subsequent extinction recall and safety recall on the last day of testing.
Veterans learned to differentiate the CS+ and the CS- on the first day of testing. Veterans who underwent safety learning more quickly on the first day of testing showed more efficient REM sleep that night ( = .607, = .028). On the second day of testing, the patients successfully underwent extinction learning. Patients with a higher percentage of REM sleep on the last night of the study showed more safety recall early on the last day of testing ( = .688, = .009).
To our knowledge, this was the first study to examine the relationship between objective sleep and fear-potentiated startle performance in veterans with PTSD. Study methods were well tolerated by participants, supporting feasibility of the experimental design. Results indicated REM sleep was associated with both initial safety learning and subsequent safety recall. Taken together with previous studies in healthy controls, these preliminary results provide additional evidence suggesting REM sleep could play a mechanistic role in the maintenance of PTSD and thus identify a modifiable biological process to target in treatment of PTSD. These findings should be replicated in larger samples.
创伤后应激障碍(PTSD)与多种负面身心健康后果相关。恐惧条件反射在PTSD中发挥着重要的机制作用,且PTSD患者在安全信号学习方面也存在缺陷。睡眠,尤其是快速眼动睡眠(REM睡眠),在动物模型和健康人类中与安全学习及消退过程的改善有关。尚无研究探讨临床人群中REM睡眠与安全信号学习或消退记忆之间的联系。
本研究调查了13名患有PTSD的退伍军人的REM睡眠、安全信号学习与消退过程之间的关系。通过多导睡眠图(PSG)在实验室对患者的夜间睡眠进行特征描述。次日,参与者接受恐惧条件反射范式,在此过程中他们对视觉线索产生恐惧。该测试环节还包括一个成为安全信号(CS-)的视觉线索。条件反射后,再次对退伍军人的睡眠进行整夜监测,之后他们接受消退训练。在第三个夜晚睡眠后,测试消退回忆和安全回忆。双变量相关性分析检验了安全信号学习斜率与后续REM睡眠之间的关系,以及测试最后一天REM睡眠与后续消退回忆和安全回忆之间的关系。
退伍军人在测试第一天学会区分CS+和CS-。在测试第一天安全学习速度更快的退伍军人当晚的REM睡眠更高效(r = 0.607,p = 0.028)。在测试第二天,患者成功进行了消退学习。在研究最后一晚REM睡眠百分比更高的患者在测试最后一天早期表现出更多的安全回忆(r = 0.688,p = 0.009)。
据我们所知,这是第一项研究PTSD退伍军人客观睡眠与恐惧增强惊吓表现之间关系的研究。研究方法参与者耐受性良好,支持了实验设计的可行性。结果表明REM睡眠与初始安全学习及后续安全回忆均相关。结合先前对健康对照的研究,这些初步结果提供了更多证据,表明REM睡眠可能在PTSD的维持中发挥机制作用,从而确定了一个可在PTSD治疗中靶向的可改变生物学过程。这些发现应在更大样本中进行重复验证。