Cholinergic Modulation of Disorder-Relevant Neural Circuits in Generalized Anxiety Disorder.

Amygdala Anxiety Disorders / drug therapy Cholinergic Agents Facial Expression Fear Humans Magnetic Resonance Imaging Male Prefrontal Cortex
Amygdala Anterior cingulate cortex Cholinergic modulation Generalized anxiety disorder Pharmacotherapy fMRI

Journal

Biological psychiatry
ISSN: 1873-2402
Titre abrégé: Biol Psychiatry
Pays: United States
ID NLM: 0213264

Informations de publication

Date de publication:
15 05 2020
Historique:
received: 21 05 2019
revised: 25 11 2019
accepted: 11 12 2019
pubmed: 29 2 2020
medline: 7 1 2021
entrez: 29 2 2020
Statut: ppublish

Résumé

Generalized anxiety disorder is associated with hyperactivity in the amygdala-prefrontal networks, and normalization of this aberrant function is thought to be critical for successful treatment. Preclinical evidence implicates cholinergic neurotransmission in the function of these systems and suggests that cholinergic modulation may have anxiolytic effects. However, the effects of cholinergic modulators on the function of anxiety-related networks in humans have not been investigated. We administered a novel α7 nicotinic acetylcholine receptor-negative allosteric modulator, BNC210, to 24 individuals (3 male subjects) with generalized anxiety disorder and assessed its effects on neural responses to fearful face stimuli. BNC210 reduced amygdala reactivity to fearful faces relative to placebo and similarly to lorazepam and also reduced connectivity between the amygdala and the anterior cingulate cortex, a network involved in regulating anxious responses to aversive stimuli. These results demonstrate for the first time that the function of disorder-relevant neural circuits in generalized anxiety disorder can be beneficially altered through modulation of cholinergic neurotransmission and suggest potential for this system as a novel target for anxiolytic pharmacotherapy.

Sections du résumé

BACKGROUND
Generalized anxiety disorder is associated with hyperactivity in the amygdala-prefrontal networks, and normalization of this aberrant function is thought to be critical for successful treatment. Preclinical evidence implicates cholinergic neurotransmission in the function of these systems and suggests that cholinergic modulation may have anxiolytic effects. However, the effects of cholinergic modulators on the function of anxiety-related networks in humans have not been investigated.
METHODS
We administered a novel α7 nicotinic acetylcholine receptor-negative allosteric modulator, BNC210, to 24 individuals (3 male subjects) with generalized anxiety disorder and assessed its effects on neural responses to fearful face stimuli.
RESULTS
BNC210 reduced amygdala reactivity to fearful faces relative to placebo and similarly to lorazepam and also reduced connectivity between the amygdala and the anterior cingulate cortex, a network involved in regulating anxious responses to aversive stimuli.
CONCLUSIONS
These results demonstrate for the first time that the function of disorder-relevant neural circuits in generalized anxiety disorder can be beneficially altered through modulation of cholinergic neurotransmission and suggest potential for this system as a novel target for anxiolytic pharmacotherapy.

Identifiants

DOI: 10.1016/j.biopsych.2019.12.013 PMID: 32107005 PMC: PMC7198974
pubmed: 32107005
pii: S0006-3223(19)31937-7
doi: 10.1016/j.biopsych.2019.12.013
pmc: PMC7198974
pii:
doi:

Substances chimiques

Cholinergic Agents 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

908-915

Subventions

Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 206460/Z/17/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P001378/1
Pays : United Kingdom

Informations de copyright

Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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Auteurs

Toby Wise (T)

Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; Wellcome Trust Centre for Neuroimaging, University College London, London, UK; Max Planck UCL Centre for Computational Psychiatry and Ageing Research, London, UK; Department of Humanities and Social Sciences, California Institute of Technology, Pasadena, California. Electronic address: t.wise@ucl.ac.uk.

Fiona Patrick (F)

Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

Nicholas Meyer (N)

Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

Ndaba Mazibuko (N)

Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

Alice E Oates (AE)

Maudsley NHS Foundation Trust, London, UK.

Anne H M van der Bijl (AHM)

Faculty of Social and Behavioural Sciences, University of Leiden, Leiden, Netherlands.

Philippe Danjou (P)

Biotrial, Paris, France.

Susan M O'Connor (SM)

Bionomics Ltd, Thebarton, Australia.

Elizabeth Doolin (E)

Bionomics Ltd, Thebarton, Australia.

Caroline Wooldridge (C)

Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

Deborah Rathjen (D)

BiOasis Technologies Inc., Guilford, Connecticut.

Christine Macare (C)

Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

Steven C R Williams (SCR)

Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; National Institute for Health Research Biomedical Research Centre, South London, London, UK.

Adam Perkins (A)

Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; National Institute for Health Research Biomedical Research Centre, South London, London, UK.

Allan H Young (AH)

Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; National Institute for Health Research Biomedical Research Centre, South London, London, UK.

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questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Prosencéphale › Télencéphale › Cerveau › Noyaux gris centraux › Amygdale (système limbique) › Cholinergic Modulation of Disorder-Relevant...
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questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Agents neuromédiateurs › Agents cholinergiques › Cholinergic Modulation of Disorder-Relevant...
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