BACKGROUND: Syndromes of fear/anxiety are currently ill-defined, with no accepted human biomarkers for anxiety-specific processes. A unique common neural action of different classes of anxiolytic drugs may provide such a biomarker. In rodents, a reduction in low frequency (4-12 Hz; "theta") brain rhythmicity is produced by all anxiolytics (even those lacking panicolytic or antidepressant action) and not by any non-anxiolytics. This rhythmicity is a key property of the Behavioural Inhibition System (BIS) postulated to be one neural substrate of anxiety. We sought homologous anxiolytic-sensitive changes in human surface EEG rhythmicity. METHOD:Thirty-four healthy volunteers in parallel groups were administered double blind single doses of triazolam 0.25mg, buspirone 10mg or placebo 1 hour prior to completing the stop-signal task. Right frontal conflict-specific EEG power (previously shown to correlate with trait anxiety and neuroticism in this task) was extracted as a contrast between trials with balanced approach-avoidance (stop-go) conflict and the average of trials with net approach and net avoidance. RESULTS: Compared with placebo, both triazolam and buspirone decreased right-frontal, 9-10 Hz, conflict-specific-power. LIMITATIONS: Only one dose of each of only two classes of anxiolytic and no non-anxiolytics were tested, so additional tests are needed to determine generality. CONCLUSIONS: There is a distinct rhythmic system in humans that is sensitive to both classical/GABAergic and novel/serotonergic anxiolytics. This conflict-specific rhythmicity should provide a biomarker, with a strong pre-clinical neuropsychology, for a novel approach to classifying anxiety disorders.
RCT Entities:
BACKGROUND: Syndromes of fear/anxiety are currently ill-defined, with no accepted human biomarkers for anxiety-specific processes. A unique common neural action of different classes of anxiolytic drugs may provide such a biomarker. In rodents, a reduction in low frequency (4-12 Hz; "theta") brain rhythmicity is produced by all anxiolytics (even those lacking panicolytic or antidepressant action) and not by any non-anxiolytics. This rhythmicity is a key property of the Behavioural Inhibition System (BIS) postulated to be one neural substrate of anxiety. We sought homologous anxiolytic-sensitive changes in human surface EEG rhythmicity. METHOD: Thirty-four healthy volunteers in parallel groups were administered double blind single doses of triazolam 0.25mg, buspirone 10mg or placebo 1 hour prior to completing the stop-signal task. Right frontal conflict-specific EEG power (previously shown to correlate with trait anxiety and neuroticism in this task) was extracted as a contrast between trials with balanced approach-avoidance (stop-go) conflict and the average of trials with net approach and net avoidance. RESULTS: Compared with placebo, both triazolam and buspirone decreased right-frontal, 9-10 Hz, conflict-specific-power. LIMITATIONS: Only one dose of each of only two classes of anxiolytic and no non-anxiolytics were tested, so additional tests are needed to determine generality. CONCLUSIONS: There is a distinct rhythmic system in humans that is sensitive to both classical/GABAergic and novel/serotonergic anxiolytics. This conflict-specific rhythmicity should provide a biomarker, with a strong pre-clinical neuropsychology, for a novel approach to classifying anxiety disorders.
Authors: Camarin E Rolle; Mads L Pedersen; Noriah Johnson; Ken-Ichi Amemori; Maria Ironside; Ann M Graybiel; Diego A Pizzagalli; Amit Etkin Journal: Cereb Cortex Date: 2022-03-04 Impact factor: 4.861
Authors: Noah S Philip; S Louisa Carpenter; Samuel J Ridout; George Sanchez; Sarah E Albright; Audrey R Tyrka; Lawrence H Price; Linda L Carpenter Journal: J Affect Disord Date: 2015-07-17 Impact factor: 4.839
Authors: Shabah Mohammad Shadli; Tame Kawe; Daniel Martin; Neil McNaughton; Shona Neehoff; Paul Glue Journal: Int J Neuropsychopharmacol Date: 2018-08-01 Impact factor: 5.176