Prefrontal Oscillations in Social Anxiety Disorder (POSAD) (POSAD)
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| ClinicalTrials.gov Identifier: NCT03821779 |
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Recruitment Status :
Recruiting
First Posted : January 30, 2019
Last Update Posted : November 26, 2019
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Anxiety Disorders Anxiety Anxiety and Fear | Behavioral: In vivo social exposure Behavioral: Social exposure in a virtual reality setting Other: EEG recording Diagnostic Test: Psychometric evaluation Diagnostic Test: Visual Analogue Scale of anxiety | Not Applicable |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 30 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Intervention Model Description: | First phase (go-no-go) with 10 subjects in 1 arm Second phase with 20 subjets (2 arms) in a cross-over design. |
| Masking: | None (Open Label) |
| Primary Purpose: | Basic Science |
| Official Title: | Study of Slow Prefrontal Cortex Oscillations During Social Exposure in Social Anxiety Disorder |
| Actual Study Start Date : | November 12, 2019 |
| Estimated Primary Completion Date : | November 10, 2021 |
| Estimated Study Completion Date : | December 10, 2021 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Group 1: Go-no-go phase
The presence of significant prefrontal oscillations in the EEG recording 2-6Hz band during in vivo social exposure (oral presentation to examiners) will be assessed in 10 subjects with social anxiety disorder. EEG will be recorded immediately before, during and after oral presentations to examiners. Psychometric evaluation will be performed prior to experimental sessions. Rating of anxiety levels will be performed by subjects using a Visual Analogue Scale of anxiety during each of the 3 experimental periods (wainting, presentation, recovery). Results of EEG recordings in the first 10 subjects will lead to continuation (presence of significant slow prefrontal oscillations during anxiety) or interruption (absence of signification oscillation) of the study. |
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. 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
Diagnostic Test: Visual Analogue Scale of anxiety Subjects will be asked to rate their anxiety levels
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Experimental: Group 2.1
In group 2.1, 10 subjects will undergo 2 sessions in a cross-over design with EEG recording immediately before, during and after:
Rating of anxiety levels will be performed by subjects using a Visual Analogue Scale of anxiety during each of the 3 experimental periods for each session. Psychometric evaluation will be performed prior to experimental sessions. |
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
Diagnostic Test: Visual Analogue Scale of anxiety Subjects will be asked to rate their anxiety levels
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Experimental: Group 2.2
In group 2.2, 10 subjects will undergo 2 sessions in a cross-over design with EEG recording immediately before, during and after:
Rating of anxiety levels will be performed by subjects using a Visual Analogue Scale of anxiety during each of the 3 experimental periods for each session. Psychometric evaluation will be performed prior to experimental sessions. |
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
Diagnostic Test: Visual Analogue Scale of anxiety Subjects will be asked to rate their anxiety levels
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- Change in power of slow oscillations in prefrontal EEG recordings during anticipation relative to baseline [ Time Frame: During the 5 minutes before oral presentation and during the 1 hour rest period ]
The change in power of PFC 2-6 Hz oscillations between the 5-minutes waiting period before oral presentation and the recovery period will be computed as a ratio.
Detection of exaggerated 2-6Hz oscillations in prefrontal cortex during anxious anticipation is the primary aim of this study.
- Duration of prefrontal slow oscillations epochs during anticipation [ Time Frame: During the 5 minutes before oral presentation ]Time-frequency analysis will be performed to determine the duration of 2-6Hz prefrontal oscillations epochs and total duration of these oscillations within experimental period. Significant oscillatory epochs will be defined using power ratios. These metrics will be used in order to assess the neurobiological and clinical relevance of this biomarker.
- Change in power of slow oscillations in prefrontal EEG recordings during presentation relative to baseline [ Time Frame: During the 5 minutes oral presentation and during the 1 hour rest period. ]The change in power of PFC 2-6 Hz oscillations between the 5-minutes oral presentation and the recovery period will be computed as a ratio.
- Duration of prefrontal slow oscillations epochs during presentation [ Time Frame: During the 5 minutes oral presentation ]Time-frequency analysis will be performed to determine the duration of 2-6Hz prefrontal oscillations epochs and total duration of these oscillations within experimental period. Significant oscillatory epochs will be defined using power ratios.
- Correlation between prefrontal slow oscillations power during anticipation and anxiety score [ Time Frame: During the 5 minutes before oral presentation ]Correlation will be calculated between PFC 2-6 Hz oscillations power and the visual Analogue anxiety score during the 5 minutes period before presentation.
- Correlation between prefrontal slow oscillations power during presentation and anxiety score [ Time Frame: During the 5 minutes oral presentation ]Correlation will be calculated between PFC 2-6 Hz oscillations power and the visual Analogue anxiety score during presentation.
- Correlation between prefrontal slow oscillations duration during anticipation and anxiety score [ Time Frame: During the 5 minutes before oral presentation ]Correlation will be calculated between PFC 2-6 Hz oscillations duration and the visual Analogue anxiety score during the 5 minutes period before presentation.
- Correlation between prefrontal slow oscillations duration during presentation and anxiety score [ Time Frame: During the 5 minutes oral presentation ]Correlation will be calculated between PFC 2-6 Hz oscillations duration and the visual Analogue anxiety score during presentation.
- Correlation between prefrontal slow oscillations power during anticipation and trait anxiety [ Time Frame: During the 5 minutes before oral presentations (PFC oscillations power) and prior to inclusion (STAI-B rating) ]Correlation will be calculated between PFC 2-6 Hz oscillations power during the 5 minutes before presentation and STAI-B scores
- Correlation between prefrontal slow oscillations power during presentation and trait anxiety [ Time Frame: During the 5 minutes oral presentation (PFC oscillations power) and prior to inclusion (STAI-B rating) ]Correlation will be calculated between PFC 2-6 Hz oscillations power during presentation and STAI-B scores
- Correlation between prefrontal slow oscillations duration during anticipation and trait anxiety [ Time Frame: During the 5 minutes before oral presentation (PFC oscillations duration) and prior to inclusion (STAI-B rating) ]Correlation will be calculated between PFC 2-6 Hz oscillations duration during the 5 minutes before presentation and STAI-B scores
- Correlation between prefrontal slow oscillations duration during presentation and trait anxiety [ Time Frame: During the 5 minutes oral presentation (PFC oscillations duration) and prior to inclusion (STAI-B rating) ]Correlation will be calculated between PFC 2-6 Hz oscillations duration during presentation and STAI-B scores
- Correlation between prefrontal slow oscillations power during anticipation and state anxiety [ Time Frame: During the 5 minutes before oral presentation (PFC oscillations power) and prior to inclusion (STAI-A rating) ]Correlation will be calculated between PFC 2-6 Hz oscillations power during the 5 minutes before presentation and STAI-A scores
- Correlation between prefrontal slow oscillations power during presentation and state anxiety [ Time Frame: During the 5 minutes oral presentation (PFC oscillations power) and prior to inclusion (STAI-A rating) ]Correlation will be calculated between PFC 2-6 Hz oscillations power during presentation and STAI-A scores
- Correlation between prefrontal slow oscillations duration during anticipation and state anxiety [ Time Frame: During the 5 minutes before oral presentation (PFC oscillations duration) and prior to inclusion (STAI-A rating) ]Correlation will be calculated between PFC 2-6 Hz oscillations duration during the 5 minutes before presentation and STAI-A scores
- Correlation between prefrontal slow oscillations duration during presentation and state anxiety [ Time Frame: During the 5 minutes oral presentation (PFC oscillations duration) and prior to inclusion (STAI-A rating) ]Correlation will be calculated between PFC 2-6 Hz oscillations duration during presentation and STAI-A scores
- Correlation between prefrontal slow oscillations power during anticipation and levels of social anxiety [ Time Frame: During the 5 minutes before oral presentation (PFC oscillations power) and prior to inclusion (LSAS rating) ]Correlation will be calculated between PFC 2-6 Hz oscillations power during the 5 minutes before presentation and LSAS scores
- Correlation between prefrontal slow oscillations power during presentation and levels of social anxiety [ Time Frame: During the 5 minutes oral presentation (PFC oscillations power) and prior to inclusion (LSAS rating) ]Correlation will be calculated between PFC 2-6 Hz oscillations power during presentation and LSAS scores
- Correlation between prefrontal slow oscillations duration during anticipation and levels of social anxiety [ Time Frame: During the 5 minutes before oral presentation (PFC oscillations duration) and prior to inclusion (LSAS rating) ]Correlation will be calculated between PFC 2-6 Hz oscillations duration during the 5 minutes before presentation and LSAS scores
- Correlation between prefrontal slow oscillations duration during presentation and levels of social anxiety [ Time Frame: During the 5 minutes oral presentation (PFC oscillations duration) and prior to inclusion (LSAS rating) ]Correlation will be calculated between PFC 2-6 Hz oscillations duration during presentation and LSAS scores
- Correlation between prefrontal slow oscillations power during anticipation and levels of general anxiety [ Time Frame: During the 5 minutes before oral presentation (PFC oscillations power) and prior to inclusion (BAS rating) ]Correlation will be calculated between PFC 2-6 Hz oscillations power during the 5 minutes before presentation and BAS scores
- Correlation between prefrontal slow oscillations power during presentation and levels of general anxiety [ Time Frame: During the 5 minutes oral presentation (PFC oscillations power) and prior to inclusion (BAS rating) ]Correlation will be calculated between PFC 2-6 Hz oscillations power during presentation and BAS scores
- Correlation between prefrontal slow oscillations duration during anticipation and levels of general anxiety [ Time Frame: During the 5 minutes before oral presentation (PFC oscillations duration) and prior to inclusion (BAS rating) ]Correlation will be calculated between PFC 2-6 Hz oscillations duration during the 5 minutes before presentation and BAS scores
- Correlation between prefrontal slow oscillations duration during presentation and levels of general anxiety [ Time Frame: During the 5 minutes oral presentation (PFC oscillations duration) and prior to inclusion (BAS rating) ]Correlation will be calculated between PFC 2-6 Hz oscillations duration during presentation and BAS scores
- Correlation between prefrontal slow oscillations power during anticipation and depression levels [ Time Frame: During the 5 minutes before oral presentation (PFC oscillations power) and prior to inclusion (MARDS rating) ]Correlation will be calculated between PFC 2-6 Hz oscillations power during the 5 minutes before presentation and MADRS scores
- Correlation between prefrontal slow oscillations power during presentation and depression levels [ Time Frame: During the 5 minutes oral presentation (PFC oscillations power) and prior to inclusion (MARDS rating) ]Correlation will be calculated between PFC 2-6 Hz oscillations power during presentations and MADRS scores
- Correlation between prefrontal slow oscillations duration during anticipation and depression levels [ Time Frame: During the 5 minutes before oral presentation (PFC oscillations duration) and prior to inclusion (MARDS rating) ]Correlation will be calculated between PFC 2-6 Hz oscillations duration during the 5 minutes before presentation and MADRS scores
- Correlation between prefrontal slow oscillations duration during presentation and depression levels [ Time Frame: During the 5 minutes oral presentations (PFC oscillations duration) and prior to inclusion (MARDS rating) ]Correlation will be calculated between PFC 2-6 Hz oscillations duration during presentation and MADRS scores
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 20 Years to 50 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Social anxiety disorder as defined in DSM-5
- Full understanding of the protocol
- Obtaining informed consent from study subjects before or at inclusion at the latest
- Being registered in the french national health insurance service (Sécurité Sociale) (or equivalent)
Exclusion Criteria:
- Active medical co-morbidity including severe hypertension, cardiac insufficiency, Raynaud syndrome, diabetes mellitus, renal insufficiency, adrenal insufficiency, Cushing syndrome and epilepsy
- Severe neurological co-morbidity, including but not limited to Parkinson's disease and multiple sclerosis
- Long-term corticotherapy
- History of significant head injury, defined by loss of consciousness
- Being diagnosed with another major psychiatric condition (DSM5) including bipolar disorder and schizophrenia or substance/alcohol use disorder; with the exception of major depressive disorder and nicotine use disorder
- Suicidal risk evaluated as moderate to high in the MINI questionnaire
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initiation of a psychotropic treatment or change in the dose of ongoing psychotropic treatment within 3 days prior to each visit and including:
- antidepressant treatments with selective serotonin recapture inhibitors, serotonin and norepinephrine inhibitors, alpha2-presynaptic adrenoreceptors (mirtazapine, mianserin), tricyclic
- anxiolytic drugs including benzodiazepines and anti-histamine
- antipsychotic drugs
- Acute alcohol intake 2 days prior to each visit (inclusion, experimental sessions)
- Pregnancy or breastfeeding.
- Ongoing hospitalization without consent (decision of a third-party: medical, justice)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03821779
| Contact: Bruno Aouizerate, MD-PhD | +33(0) 5 56 56 17 98 | bruno.aouizerate@u-bordeaux.fr | |
| Contact: Cyril Herry, PhD | 33(0)5 57 57 37 26 | cyril.herry@inserm.fr |
| France | |
| GENPHASS, SANPSY, CHU de Bordeaux | Recruiting |
| Bordeaux, France, 33076 | |
| Contact: Pierre Philip, MD-PhD +33 5 57 82 01 73 pierre.philip@chu-bordeaux.fr | |
| Contact: Jacques Taillard, MS jacques.taillard@chu-bordeaux.fr | |
| Principal Investigator: | Olivier Doumy, MD | Centre Hospitalier Charles Perrens, Bordeaux; INRA NutriNeuro, Bordeaux; Université de Bordeaux, France | |
| Principal Investigator: | Alexandra Bouvard, MD | Centre Hospitalier Charles Perrens, Bordeaux; Université de Bordeaux, France | |
| Study Director: | Cyril Herry, PhD | Neurocentre Magendie, Inserm U1215, Bordeaux, France | |
| Principal Investigator: | Cyril Dejean, PhD | Neurocentre Magendie, Inserm U1215, Bordeaux, France | |
| Principal Investigator: | Thomas Bienvenu, PhD | Centre Hospitalier Charles Perrens, Bordeaux; Neurocentre Magendie, Inserm U1215, Bordeaux, France | |
| Principal Investigator: | Jacques Taillard, MS | GENPHASS, CHU de Bordeaux | |
| Study Chair: | Bruno Aouizerate, MD-PhD | Centre Hospitalier Charles Perrens, Bordeaux; INRA NutriNeuro, Bordeaux; Université de Bordeaux, France |
| Responsible Party: | Institut National de la Santé Et de la Recherche Médicale, France |
| ClinicalTrials.gov Identifier: | NCT03821779 |
| Other Study ID Numbers: |
C17-25 |
| First Posted: | January 30, 2019 Key Record Dates |
| Last Update Posted: | November 26, 2019 |
| Last Verified: | November 2019 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Anxiety Disorders Phobia, Social Mental Disorders Phobic Disorders |