Acute Angiotensin II Receptor Blockade Facilitates Parahippocampal Processing During Memory Encoding in High-Trait-Anxious Individuals

• Published in: Biological psychiatry global open science Vol. 4; no. 2; p. 100286
• Main Authors: Shkreli, Lorika, Thoroddsen, Theodora, Kobelt, Malte, Martens, Marieke A.G., Browning, Michael, Harmer, Catherine J., Cowen, Phil, Reinecke, Andrea
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2024; Elsevier
• Subjects: Angiotensin II receptor blocker; Archival Report; Losartan; Memory encoding; Parahippocampus; Pattern-similarity analysis; Posttraumatic stress disorder; Pattern-similarity analysis; Parahippocampus; Memory encoding; Posttraumatic stress disorder; Angiotensin II receptor blocker; Losartan
• ISSN: 2667-1743; 2667-1743
• DOI: 10.1016/j.bpsgos.2023.100286

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. It has increasingly become evident that angiotensin receptors may represent a novel pharmacological target for anxiety and posttraumatic stress disorder. In this study, Shkreli et al. investigated the effects of the angiotensin receptor blocker losartan on neural markers of memory formation, including multivariate pattern similarity analysis. The authors show that during memory formation, losartan enhanced activation and neural stability in the parahippocampal gyrus—a brain area involved in higher-order visual processing. Potential mechanisms and implications for posttraumatic stress disorder are discussed.