File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Human Extinction Learning Is Accelerated by an Angiotensin Antagonist via Ventromedial Prefrontal Cortex and Its Connections With Basolateral Amygdala

TitleHuman Extinction Learning Is Accelerated by an Angiotensin Antagonist via Ventromedial Prefrontal Cortex and Its Connections With Basolateral Amygdala
Authors
KeywordsAngiotensin
Anxiety disorders
Extinction
fMRI
Functional magnetic resonance imaging
Losartan
Ventromedial prefrontal cortex
vmPFC
Issue Date2019
Citation
Biological Psychiatry, 2019, v. 86, n. 12, p. 910-920 How to Cite?
AbstractBackground: Deficient extinction learning and threat adaptation in the ventromedial prefrontal cortex (vmPFC)-amygdala circuitry strongly impede the efficacy of exposure-based interventions in anxiety disorders. Recent animal models suggest a regulatory role of the renin-angiotensin system in both these processes. Against this background, the present randomized placebo-controlled pharmacologic functional magnetic resonance imaging experiment aimed at determining the extinction enhancing potential of the angiotensin II type 1 receptor antagonist losartan (LT) in humans. Methods: Seventy healthy male subjects underwent Pavlovian threat conditioning and received single-dose LT (50 mg) or placebo administration before extinction. Psychophysiological threat reactivity (skin conductance response) and neural activity during extinction served as primary outcomes. Psychophysiological interaction, voxelwise mediation, and novel multivariate pattern classification analyses were used to determine the underlying neural mechanisms. Results: LT significantly accelerated the decline of the psychophysiological threat response during within-session extinction learning. On the neural level, the acceleration was accompanied and critically mediated by threat-specific enhancement of vmPFC activation. Furthermore, LT enhanced vmPFC-basolateral amygdala coupling and attenuated the neural threat expression, particularly in the vmPFC, during early extinction. Conclusions: Overall the results indicate that LT facilitates within-session threat memory extinction by augmenting threat-specific encoding in the vmPFC and its regulatory control over the amygdala. The findings document a pivotal role of angiotensin regulation of extinction learning in humans and suggest that adjunct LT administration has the potential to facilitate the efficacy of exposure-based interventions in anxiety disorders.
Persistent Identifierhttp://hdl.handle.net/10722/330615
ISSN
2023 Impact Factor: 9.6
2023 SCImago Journal Rankings: 3.786
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhou, Feng-
dc.contributor.authorGeng, Yayuan-
dc.contributor.authorXin, Fei-
dc.contributor.authorLi, Jialin-
dc.contributor.authorFeng, Pan-
dc.contributor.authorLiu, Congcong-
dc.contributor.authorZhao, Weihua-
dc.contributor.authorFeng, Tingyong-
dc.contributor.authorGuastella, Adam J.-
dc.contributor.authorEbstein, Richard P.-
dc.contributor.authorKendrick, Keith M.-
dc.contributor.authorBecker, Benjamin-
dc.date.accessioned2023-09-05T12:12:20Z-
dc.date.available2023-09-05T12:12:20Z-
dc.date.issued2019-
dc.identifier.citationBiological Psychiatry, 2019, v. 86, n. 12, p. 910-920-
dc.identifier.issn0006-3223-
dc.identifier.urihttp://hdl.handle.net/10722/330615-
dc.description.abstractBackground: Deficient extinction learning and threat adaptation in the ventromedial prefrontal cortex (vmPFC)-amygdala circuitry strongly impede the efficacy of exposure-based interventions in anxiety disorders. Recent animal models suggest a regulatory role of the renin-angiotensin system in both these processes. Against this background, the present randomized placebo-controlled pharmacologic functional magnetic resonance imaging experiment aimed at determining the extinction enhancing potential of the angiotensin II type 1 receptor antagonist losartan (LT) in humans. Methods: Seventy healthy male subjects underwent Pavlovian threat conditioning and received single-dose LT (50 mg) or placebo administration before extinction. Psychophysiological threat reactivity (skin conductance response) and neural activity during extinction served as primary outcomes. Psychophysiological interaction, voxelwise mediation, and novel multivariate pattern classification analyses were used to determine the underlying neural mechanisms. Results: LT significantly accelerated the decline of the psychophysiological threat response during within-session extinction learning. On the neural level, the acceleration was accompanied and critically mediated by threat-specific enhancement of vmPFC activation. Furthermore, LT enhanced vmPFC-basolateral amygdala coupling and attenuated the neural threat expression, particularly in the vmPFC, during early extinction. Conclusions: Overall the results indicate that LT facilitates within-session threat memory extinction by augmenting threat-specific encoding in the vmPFC and its regulatory control over the amygdala. The findings document a pivotal role of angiotensin regulation of extinction learning in humans and suggest that adjunct LT administration has the potential to facilitate the efficacy of exposure-based interventions in anxiety disorders.-
dc.languageeng-
dc.relation.ispartofBiological Psychiatry-
dc.subjectAngiotensin-
dc.subjectAnxiety disorders-
dc.subjectExtinction-
dc.subjectfMRI-
dc.subjectFunctional magnetic resonance imaging-
dc.subjectLosartan-
dc.subjectVentromedial prefrontal cortex-
dc.subjectvmPFC-
dc.titleHuman Extinction Learning Is Accelerated by an Angiotensin Antagonist via Ventromedial Prefrontal Cortex and Its Connections With Basolateral Amygdala-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.biopsych.2019.07.007-
dc.identifier.pmid31471037-
dc.identifier.scopuseid_2-s2.0-85071272471-
dc.identifier.volume86-
dc.identifier.issue12-
dc.identifier.spage910-
dc.identifier.epage920-
dc.identifier.eissn1873-2402-
dc.identifier.isiWOS:000496956100008-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats