NCT03821779

Prefrontal Oscillations in Social Anxiety Disorder (POSAD)

Study of Slow Prefrontal Cortex Oscillations During Social Exposure in Social Anxiety Disorder

• Status: Active Not Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France · Other Government
• Sex: All
• Age: 20 Years – 50 Years
• Healthy volunteers: Not accepted

Summary

Experimental fear in rodents is correlated with slow oscillations in electrical recordings of prefrontal cortex activities. The present study aims to test whether slow prefrontal oscillations is a biomarker of pathological anxiety in human subjects.

Detailed description

Fear and anxiety are adaptive responses that may become excessive or inappropriate in pathological conditions, as defined as anxiety disorders in DSM-5. These disorders, including phobic disorders such as social anxiety disorder, are frequent and impairing in the general population, with an estimated lifetime prevalence of 28% and significant consequences on quality of life. Direct and indirect medical costs related to these conditions amount to 74.4 billion €/year in Europe. Despite their prevalence, debilitating nature and chronicity, the pathophysiology of anxiety disorders is poorly understood and neurobiological treatments, including pharmacotherapy, are lacking efficacy. A better understanding of the neuronal mechanisms implicated in anxiety is necessary for the conception of new approaches to treat pathological anxiety. Anxiety is commonly modeled in animals using fear conditioning, which consists in associating a neutral stimulus (eg: a sound) with a mild electrical foot-shock. As a result of the association between sound and shock, sound presentation in isolation induces a set of conditioned behavioral responses, such as an immobilization ("freezing"). Previous studies have shown that the expression of fear responses, measured on the basis of freezing, is associated with the emergence of slow oscillations (2-6Hz) in medial prefrontal cortex (mPFC) of mice. Moreover, emergence of these oscillations in mPFC is predictive of the occurrence of freezing, and the artificial induction of 4 Hz oscillations in mPFC with optogenetics induces freezing. Finally, inhibiting neurons in mPFC during the ascending phase of this slow mPFC oscillation at the time of conditioned sound presentation is sufficient to significantly reduce fear. Interestingly, these results obtained in mice seem to find their prolongation in humans. Recent studies using fear conditioning in human subjects have also reported the emergence of prefrontal slow oscillations between 2-6 Hz during expression of conditioned fear responses. These results suggests that common mechanisms underlie the expression of fear in humans and rodents. However, whether similar neuronal circuits and mechanisms are implicated in human anxiety disorders remains unknown. This study aims at assessing the presence of slow mPFC oscillations during expression of anxiety in patients suffering from anxiety disorders. Beyond understanding of the neuronal mechanisms underlying anxiety expression, this study could provide a biomarker of anxiety with diagnostic and therapeutic implications.

Conditions

• Anxiety Disorders
• Anxiety
• Anxiety and Fear

Interventions

Type	Name	Description
BEHAVIORAL	In vivo social exposure	Subjects will be invited to give a 5 minutes oral presentation on the topic of their choice to five examiners displaying no facial emotional reaction, after a 5 minutes period of silent waiting in front of the examiners. This waiting period is prompt to elicit anticipation-type of social anxiety.
BEHAVIORAL	Social exposure in a virtual reality setting	Subjects will give a 5 minutes oral presentation on the subject of their choice to a virtual reality panel composed of 5 examiners displaying no facial emotional reaction, after a 5 minutes period of silent waiting in front of the examiners. This waiting period is expected to elicit anticipation-type of social anxiety.
OTHER	EEG recording	EEG will be recorded with a standard 16-electrodes cap. Recordings will start before the 5 minutes waiting period and continue throughout oral presentation and recovery. The recovery period will be used as a baseline control
DIAGNOSTIC_TEST	Psychometric evaluation	Subjects will be evaluated prior to inclusion using the following assessment tools * Anamnestic Association for Methodology and Documentation in Psychiatry (AMDP) questionnaire * Mini International Neuropsychiatric Interview (MINI 6.0, for psychiatric diagnoses) * Liebowitz Social Anxiety Scale (LSAS) * Montgomery Asberg Depression Rating Scale (MADRS) * Brief Anxiety Scale of Tyrer (BAS) * State-Trait Anxiety Inventory (STAI A-B) * Global Assessment of Functioning (GAF)
DIAGNOSTIC_TEST	Visual Analogue Scale of anxiety	Subjects will be asked to rate their anxiety levels * immediately before (5 minutes of silent waiting), * during * and after the 5-minute oral presentation (recovery)

Timeline

• Start date: 2019-11-12
• Primary completion: 2025-11-08
• Completion: 2026-05-09
• First posted: 2019-01-30
• Last updated: 2026-02-13

Locations

1 site across 1 country: France