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

Research output: Contribution to journalArticle

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Cholinergic Modulation of Disorder-Relevant Neural Circuits in Generalized Anxiety Disorder. / Wise, Toby; Patrick, Fiona; Meyer, Nicholas; Mazibuko, Ndaba; Oates, Alice E; van der Bijl, Anne H M; Danjou, Philippe; O'Connor, Susan M; Doolin, Elizabeth; Wooldridge, Caroline; Rathjen, Deborah; Macare, Christine; Williams, Steven C R; Perkins, Adam; Young, Allan H.

In: Biological psychiatry, Vol. 87, No. 10, 15.05.2020, p. 908-915.

Research output: Contribution to journalArticle

Harvard

Wise, T, Patrick, F, Meyer, N, Mazibuko, N, Oates, AE, van der Bijl, AHM, Danjou, P, O'Connor, SM, Doolin, E, Wooldridge, C, Rathjen, D, Macare, C, Williams, SCR, Perkins, A & Young, AH 2020, 'Cholinergic Modulation of Disorder-Relevant Neural Circuits in Generalized Anxiety Disorder', Biological psychiatry, vol. 87, no. 10, pp. 908-915. https://doi.org/10.1016/j.biopsych.2019.12.013

APA

Wise, T., Patrick, F., Meyer, N., Mazibuko, N., Oates, A. E., van der Bijl, A. H. M., ... Young, A. H. (2020). Cholinergic Modulation of Disorder-Relevant Neural Circuits in Generalized Anxiety Disorder. Biological psychiatry, 87(10), 908-915. https://doi.org/10.1016/j.biopsych.2019.12.013

Vancouver

Wise T, Patrick F, Meyer N, Mazibuko N, Oates AE, van der Bijl AHM et al. Cholinergic Modulation of Disorder-Relevant Neural Circuits in Generalized Anxiety Disorder. Biological psychiatry. 2020 May 15;87(10):908-915. https://doi.org/10.1016/j.biopsych.2019.12.013

Author

Wise, Toby ; Patrick, Fiona ; Meyer, Nicholas ; Mazibuko, Ndaba ; Oates, Alice E ; van der Bijl, Anne H M ; Danjou, Philippe ; O'Connor, Susan M ; Doolin, Elizabeth ; Wooldridge, Caroline ; Rathjen, Deborah ; Macare, Christine ; Williams, Steven C R ; Perkins, Adam ; Young, Allan H. / Cholinergic Modulation of Disorder-Relevant Neural Circuits in Generalized Anxiety Disorder. In: Biological psychiatry. 2020 ; Vol. 87, No. 10. pp. 908-915.

Bibtex Download

@article{1066127e84ea486f8a8d01705d1e0e80,
title = "Cholinergic Modulation of Disorder-Relevant Neural Circuits in Generalized Anxiety Disorder",
abstract = "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.",
keywords = "Amygdala, Anterior cingulate cortex, Cholinergic modulation, Generalized anxiety disorder, Pharmacotherapy, fMRI",
author = "Toby Wise and Fiona Patrick and Nicholas Meyer and Ndaba Mazibuko and Oates, {Alice E} and {van der Bijl}, {Anne H M} and Philippe Danjou and O'Connor, {Susan M} and Elizabeth Doolin and Caroline Wooldridge and Deborah Rathjen and Christine Macare and Williams, {Steven C R} and Adam Perkins and Young, {Allan H}",
note = "Copyright {\circledC} 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.",
year = "2020",
month = "5",
day = "15",
doi = "10.1016/j.biopsych.2019.12.013",
language = "English",
volume = "87",
pages = "908--915",
journal = "Biological psychiatry",
issn = "0006-3223",
publisher = "Elsevier",
number = "10",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Cholinergic Modulation of Disorder-Relevant Neural Circuits in Generalized Anxiety Disorder

AU - Wise, Toby

AU - Patrick, Fiona

AU - Meyer, Nicholas

AU - Mazibuko, Ndaba

AU - Oates, Alice E

AU - van der Bijl, Anne H M

AU - Danjou, Philippe

AU - O'Connor, Susan M

AU - Doolin, Elizabeth

AU - Wooldridge, Caroline

AU - Rathjen, Deborah

AU - Macare, Christine

AU - Williams, Steven C R

AU - Perkins, Adam

AU - Young, Allan H

N1 - Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

PY - 2020/5/15

Y1 - 2020/5/15

N2 - 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.

AB - 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.

KW - Amygdala

KW - Anterior cingulate cortex

KW - Cholinergic modulation

KW - Generalized anxiety disorder

KW - Pharmacotherapy

KW - fMRI

UR - http://www.scopus.com/inward/record.url?scp=85080033143&partnerID=8YFLogxK

U2 - 10.1016/j.biopsych.2019.12.013

DO - 10.1016/j.biopsych.2019.12.013

M3 - Article

C2 - 32107005

VL - 87

SP - 908

EP - 915

JO - Biological psychiatry

JF - Biological psychiatry

SN - 0006-3223

IS - 10

ER -

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