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

Toby Wise, Fiona Patrick, Nicholas Meyer, Ndaba Mazibuko, Alice E Oates, Anne H M van der Bijl, Philippe Danjou, Susan M O'Connor, Elizabeth Doolin, Caroline Wooldridge, Deborah Rathjen, Christine Macare, Steven C R Williams, Adam Perkins, Allan H Young

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)
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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.

Original languageEnglish
Article numberBPS-D-19-00755R1
Pages (from-to)908-915
Number of pages8
JournalBiological psychiatry
Volume87
Issue number10
Early online date8 Jan 2020
DOIs
Publication statusPublished - 15 May 2020

Keywords

  • Amygdala
  • Anterior cingulate cortex
  • Cholinergic modulation
  • Generalized anxiety disorder
  • Pharmacotherapy
  • fMRI

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