Shkreli Lorika, Thoroddsen Theodora, Kobelt Malte, Martens Marieke A G, Browning Michael, Harmer Catherine J, Cowen Phil, Reinecke Andrea
Department of Psychiatry, University of Oxford, Oxford, United Kingdom.
Institute of Cognitive Neuroscience, Ruhr-Universität Bochum, Bochum, Germany.
Biol Psychiatry Glob Open Sci. 2023 Dec 25;4(2):100286. doi: 10.1016/j.bpsgos.2023.100286. eCollection 2024 Mar.
Angiotensin II receptor blockers (ARBs) have been associated with preventing posttraumatic stress disorder symptom development and improving memory. However, the underlying neural mechanisms are poorly understood. This study investigated ARB effects on memory encoding and hippocampal functioning that have previously been implicated in posttraumatic stress disorder development.
In a double-blind randomized design, 40 high-trait-anxious participants (33 women) received the ARB losartan (50 mg) or placebo. At drug peak level, participants encoded images of animals and landscapes before undergoing functional magnetic resonance imaging, where they viewed the encoded familiar images and unseen novel images to be memorized and classified as animals/landscapes. Memory recognition was assessed 1 hour after functional magnetic resonance imaging. To analyze neural effects, whole-brain analysis, hippocampus region-of-interest analysis, and exploratory multivariate pattern similarity analysis were employed.
ARBs facilitated parahippocampal processing. In the whole-brain analysis, losartan enhanced brain activity for familiar images in the parahippocampal gyrus (PHC), anterior cingulate cortex, and caudate. For novel images, losartan enhanced brain activity in the PHC only. Pattern similarity analysis showed that losartan increased neural stability in the PHC when processing novel and familiar images. However, there were no drug effects on memory recognition or hippocampal activation.
Given that the hippocampus receives major input from the PHC, our findings suggest that ARBs may modulate higher-order visual processing through parahippocampal involvement, potentially preserving intact memory input. Future research needs to directly investigate whether this effect may underlie the preventive effects of ARBs in the development of posttraumatic stress disorder.
血管紧张素II受体阻滞剂（ARBs）与预防创伤后应激障碍症状发展及改善记忆有关。然而，其潜在的神经机制尚不清楚。本研究调查了ARBs对记忆编码和海马功能的影响，而海马功能先前已被认为与创伤后应激障碍的发展有关。
在一项双盲随机设计中，40名高特质焦虑参与者（33名女性）接受ARB氯沙坦（50毫克）或安慰剂。在药物达到峰值水平时，参与者对动物和风景图像进行编码，然后进行功能磁共振成像，在此过程中他们观看已编码的熟悉图像和待记忆并分类为动物/风景的未见新图像。在功能磁共振成像1小时后评估记忆识别。为了分析神经效应，采用了全脑分析、海马感兴趣区域分析和探索性多变量模式相似性分析。
ARBs促进了海马旁区域的处理。在全脑分析中，氯沙坦增强了海马旁回（PHC）、前扣带回皮质和尾状核中熟悉图像的脑活动。对于新图像，氯沙坦仅增强了PHC中的脑活动。模式相似性分析表明，氯沙坦在处理新图像和熟悉图像时增加了PHC中的神经稳定性。然而，药物对记忆识别或海马激活没有影响。
鉴于海马从PHC接收主要输入，我们的研究结果表明，ARBs可能通过海马旁参与调节高阶视觉处理，潜在地保持完整的记忆输入。未来的研究需要直接调查这种效应是否可能是ARBs在创伤后应激障碍发展中的预防作用的基础。
