期刊
BIOLOGICAL PSYCHIATRY
卷 87, 期 10, 页码 908-915出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2019.12.013
关键词
Amygdala; Anterior cingulate cortex; Cholinergic modulation; Generalized anxiety disorder; fMRI; Pharmacotherapy
资金
- Bionomics Ltd
- National Institute for Health Research Biomedical Research Centre at the South London and Maudsley National Health Service Foundation Trust and King's College London
- National Institute for Health Research Biomedical Research Centre and South London and Maudsley National Health Service Foundation Trust and King's College London
- Wellcome Trust
- MRC [MR/P001378/1] Funding Source: UKRI
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 alpha 7 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.
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