Abstract
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.
Keywords
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Article info
Publication history
Published online: September 26, 2022
Accepted:
September 19,
2022
Received in revised form:
August 23,
2022
Received:
June 30,
2022
Identification
Copyright
© 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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Access this article on ScienceDirectLinked Article
- Using Multivariate Neurofunctional Signatures to Dissect the Specific Mental Processes Modulated by Novel Pharmacological TargetsBiological Psychiatry: Cognitive Neuroscience and NeuroimagingVol. 8Issue 3
- PreviewAt a time when the pharmaceutical industry has reduced investment in the discovery of new psychotropic medications, Zhang et al. (1) show how new approaches based on advances in brain imaging analysis methods can facilitate drug discovery. Specifically, they identify the angiotensin II type 1 receptor (AT1R) pathway as a promising novel target for the modulation of subjective fear experience in humans.
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