Angiotensin II Regulates the Neural Expression of Subjective Fear in Humans: A Precision Pharmaco-Neuroimaging Approach.

Humans Angiotensin II / pharmacology Losartan / pharmacology Fear / physiology Neuroimaging Amygdala Angiotensin II Type 1 Receptor Blockers / pharmacology
Angiotensin Anxiety Fear Losartan MVPA Pharmacology fMRI

Journal

Biological psychiatry. Cognitive neuroscience and neuroimaging
ISSN: 2451-9030
Titre abrégé: Biol Psychiatry Cogn Neurosci Neuroimaging
Pays: United States
ID NLM: 101671285

Informations de publication

Date de publication:
03 2023
Historique:
received: 30 06 2022
revised: 23 08 2022
accepted: 19 09 2022
pubmed: 30 9 2022
medline: 11 3 2023
entrez: 29 9 2022
Statut: ppublish

Résumé

Rodent models and pharmacological neuroimaging studies in humans have been used to test novel pharmacological agents to reduce fear. However, these strategies are limited with respect to determining process-specific effects on the actual subjective experience of fear, which represents the key symptom that motivates patients to seek treatment. In this study, we used a novel precision pharmacological functional magnetic resonance imaging approach based on process-specific neuroaffective signatures to determine effects of the selective angiotensin II type 1 receptor (AT1R) antagonist losartan on the subjective experience of fear. In a double-blind, placebo-controlled, randomized pharmacological functional magnetic resonance imaging design, healthy participants (N = 87) were administered 50 mg losartan or placebo before they underwent an oddball paradigm that included neutral, novel, and fear oddballs. Effects of losartan on brain activity and connectivity as well as on process-specific multivariate neural signatures were examined. AT1R blockade selectively reduced neurofunctional reactivity to fear-inducing visual oddballs in terms of attenuating dorsolateral prefrontal activity and amygdala-ventral anterior cingulate communication. Neurofunctional decoding further demonstrated fear-specific effects in that AT1R blockade reduced the neural expression of subjective fear but not of threat or nonspecific negative affect and did not influence reactivity to novel oddballs. These results show a specific role of the AT1R in regulating the subjective fear experience and demonstrate the feasibility of a precision pharmacological functional magnetic resonance imaging approach to the affective characterization of novel receptor targets for fear in humans.

Sections du résumé

BACKGROUND
Rodent models and pharmacological neuroimaging studies in humans have been used to test novel pharmacological agents to reduce fear. However, these strategies are limited with respect to determining process-specific effects on the actual subjective experience of fear, which represents the key symptom that motivates patients to seek treatment. In this study, we used a novel precision pharmacological functional magnetic resonance imaging approach based on process-specific neuroaffective signatures to determine effects of the selective angiotensin II type 1 receptor (AT1R) antagonist losartan on the subjective experience of fear.
METHODS
In a double-blind, placebo-controlled, randomized pharmacological functional magnetic resonance imaging design, healthy participants (N = 87) were administered 50 mg losartan or placebo before they underwent an oddball paradigm that included neutral, novel, and fear oddballs. Effects of losartan on brain activity and connectivity as well as on process-specific multivariate neural signatures were examined.
RESULTS
AT1R blockade selectively reduced neurofunctional reactivity to fear-inducing visual oddballs in terms of attenuating dorsolateral prefrontal activity and amygdala-ventral anterior cingulate communication. Neurofunctional decoding further demonstrated fear-specific effects in that AT1R blockade reduced the neural expression of subjective fear but not of threat or nonspecific negative affect and did not influence reactivity to novel oddballs.
CONCLUSIONS
These results show a specific role of the AT1R in regulating the subjective fear experience and demonstrate the feasibility of a precision pharmacological functional magnetic resonance imaging approach to the affective characterization of novel receptor targets for fear in humans.

Identifiants

DOI: 10.1016/j.bpsc.2022.09.008 PMID: 36174930
pubmed: 36174930
pii: S2451-9022(22)00237-3
doi: 10.1016/j.bpsc.2022.09.008
pii:
doi:

Substances chimiques

Angiotensin II 11128-99-7
Losartan JMS50MPO89
Angiotensin II Type 1 Receptor Blockers 0

Types de publication

Randomized Controlled Trial Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

262-270

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Auteurs

Ran Zhang (R)

Center of Psychosomatic Medicine, Sichuan Provincial Center for Mental Health, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China; Ministry of Education, Key Laboratory for Neuroinformation, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China.

Weihua Zhao (W)

Ministry of Education, Key Laboratory for Neuroinformation, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China.

Ziyu Qi (Z)

Center of Psychosomatic Medicine, Sichuan Provincial Center for Mental Health, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China; Ministry of Education, Key Laboratory for Neuroinformation, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China.

Ting Xu (T)

Center of Psychosomatic Medicine, Sichuan Provincial Center for Mental Health, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China; Ministry of Education, Key Laboratory for Neuroinformation, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China.

Feng Zhou (F)

Faculty of Psychology, Southwest University, ChongQing, China; Key Laboratory of Cognition and Personality, Ministry of Education, ChongQing, China. Electronic address: zhou.feng@live.com.

Benjamin Becker (B)

Center of Psychosomatic Medicine, Sichuan Provincial Center for Mental Health, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China; Ministry of Education, Key Laboratory for Neuroinformation, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China. Electronic address: ben_becker@gmx.de.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Angiotensin II Regulates the Neural Expression...
questionsmedicales.fr › Facteurs biologiques › Médiateurs de l'inflammation › Autacoïdes › Angiotensines › Angiotensine-II › Angiotensin II Regulates the Neural Expression...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Azoles › Tétrazoles › Losartan › Angiotensin II Regulates the Neural Expression...
questionsmedicales.fr › Comportement et mécanismes comportementaux › Émotions › Peur › Angiotensin II Regulates the Neural Expression...
questionsmedicales.fr › Techniques d'investigation › Neuroimagerie › Angiotensin II Regulates the Neural Expression...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Prosencéphale › Télencéphale › Cerveau › Noyaux gris centraux › Amygdale (système limbique) › Angiotensin II Regulates the Neural Expression...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Mécanismes moléculaires de l'action pharmacologique › Antagonistes des récepteurs aux angiotensines › Antagonistes du récepteur de type 1 de l'angiotensine-II › Angiotensin II Regulates the Neural Expression...