The angiotensin-II antagonist losartan is a promising candidate that has enhanced extinction in a post-traumatic stress disorder (PTSD) animal model and was related to reducing PTSD symptom development in humans. Here, we investigate the neurocognitive mechanisms underlying these results, testing the effect of losartan on data-driven and contextual processing of traumatic material, mechanisms proposed to be relevant for PTSD development. In a double-blind between-subject design, 40 healthy participants were randomised to a single oral dose of losartan (50 mg) or placebo, 1 h before being exposed to distressing films as a trauma analogue while heart rate (HR) was measured. Peritraumatic processing was investigated using blurry picture stimuli from the films, which transformed into clear images. Data-driven processing was measured by the level of blurriness at which contents were recognised. Contextual processing was measured as the amount of context information retrieved when describing the pictures' contents. Negative-matched control images were used to test perceptual processing of peripheral trauma-cues. Post-traumatic stress symptoms were assessed via self-report questionnaires after analogue trauma and an intrusion diary completed over 4 days following the experiment. Compared to placebo, losartan facilitated contextual processing and enhanced detail perception in the negative-match pictures. During the films, the losartan group recorded lower HR and higher HR variability, reflecting lower autonomic stress responses. We discuss potential mechanisms of losartan in preventing PTSD symptomatology, including the role of reduced arousal and increased contextual processing during trauma exposure, as well as increased threat-safety differentiation when encountering peripheral trauma-cues in the aftermaths of traumatic events.

中文翻译：

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血管紧张素参与创伤处理——探索预防创伤后应激症状的候选神经认知机制。

血管紧张素-II 拮抗剂氯沙坦是一种很有前景的候选药物，它在创伤后应激障碍 (PTSD) 动物模型中具有增强的消退作用，并且与减少人类 PTSD 症状的发展有关。在这里，我们研究了这些结果背后的神经认知机制，测试了氯沙坦对创伤材料的数据驱动和上下文处理的影响，这些机制被认为与 PTSD 发展相关。在双盲受试者间设计中，40 名健康参与者被随机分配到单次口服剂量的氯沙坦（50 毫克）或安慰剂组，在暴露于令人痛苦的电影作为创伤类似物之前 1 小时，同时测量心率 (HR)。使用来自电影的模糊图片刺激来研究围创伤处理，将其转化为清晰的图像。数据驱动的处理是通过识别内容的模糊程度来衡量的。上下文处理被测量为在描述图片内容时检索到的上下文信息量。负匹配控制图像用于测试外周创伤线索的感知处理。创伤后应激症状通过模拟创伤后的自我报告问卷和实验后 4 天完成的入侵日记进行评估。与安慰剂相比，氯沙坦促进了背景处理并增强了阴性匹配图片中的细节感知。在电影期间，氯沙坦组记录了较低的 HR 和较高的 HR 变异性，反映了较低的自主神经应激反应。我们讨论了氯沙坦预防 PTSD 症状的潜在机制，