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Angiotensin II regulates anxiety and social-affective top-down and bottom-up attention control in a sex-dependent manner.

Mengfan Han·Kun Fu·Wenyi Dong·Junjie Wang·Dan Liu·Qian Zhuang·Xiaolei Xu·Stefania Ferraro·Ting Xu·Keith M Kendrick·Dezhong Yao·Wing Chung Chang·Benjamin Becker
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Abstract

BACKGROUND: The renin-angiotensin system (RAS) has been increasingly recognized as potent modulator of cognitive and affective functions, with angiotensin II type 1 receptor (AT1R) antagonists emerging as repurposing candidate for anxiety and stress-related disorders. However, it remains unclear whether transient AT1R blockade modulates emotional attentional control and whether these effects are sex-dependent. METHODS: We conducted a preregistered, randomized, double-blind, placebo-controlled pharmacological eye-tracking study in 79 healthy adults (males and females) and determined effects of transient AT1R blockade via losartan (50 mg) on emotional attention control using a validated anti-saccade paradigm with social (emotional faces) and non-social stimuli. Treatment effects on state anxiety and oculomotor responses were characterized using traditional metrics and a novel trial-history informed dynamic control framework. RESULTS: Losartan reduced state anxiety irrespective of sex but induced sexually dimorphic effects on attentional control. In females, losartan enhanced performance by reducing endpoint error without altering latency. Conversely, in males, losartan increased endpoint error and prolonged latency of the first correct saccade. Trial-history analyses revealed losartan reduced error probabilities following errors and repeat trials in both sexes. Yet, following correct trials, females receiving losartan maintained lower error probabilities, while males exhibited higher errors, potentially reflecting failure to disengage from effortful control. CONCLUSIONS: The RAS modulates anxiety and attentional control, the latter sex-dependently. AT1R blockade reconfigures attentional processing and adaptive control, suggesting sex-specific therapeutic potential in disorders characterized by excessive anxiety and attentional dysregulation. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov; https://clinicaltrials.gov/;NCT06329050.

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HumansMaleFemaleLosartanAttentionDouble-Blind MethodAngiotensin II Type 1 Receptor BlockersAnxietyAdultAngiotensin IISex FactorsSaccadesYoung AdultRenin-Angiotensin SystemEmotionsEye-Tracking TechnologySex CharacteristicsAnti-saccadePost-error adjustmentRenin-angiotensinSex differencesStimulus switchingTrial-history effectsJournal ArticleRandomized Controlled Trial

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Mengfan Han, Kun Fu, Wenyi Dong, Junjie Wang, Dan Liu, Qian Zhuang, Xiaolei Xu, Stefania Ferraro, Ting Xu, Keith M Kendrick, Dezhong Yao, Wing Chung Chang, Benjamin Becker. 2026-07-13. Angiotensin II regulates anxiety and social-affective top-down and bottom-up attention control in a sex-dependent manner.. https://doi.org/10.1016/j.jad.2026.122254

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Journal Article; Randomized Controlled Trial resourceAdult subjectAngiotensin II subjectAngiotensin II Type 1 Receptor Blockers subjectAnti-saccade subjectAnxiety subjectAttention subjectDouble-Blind Method subjectEmotions subjectEye-Tracking Technology subjectFemale subjectHumans subjectJournal Article subjectLosartan subjectMale subjectRandomized controlled trials study

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