Study of Slow Prefrontal Cortex Oscillations During Social Exposure in Social Anxiety Disorder
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Change in power of slow oscillations in prefrontal EEG recordings during anticipation relative to baseline
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
- •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)
研究组 & 干预措施
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:
- "real exposure": oral presentation to a panel of examiners
- "virtual reality" : oral presentation to virtual examiners
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.
干预措施: In vivo social exposure (Behavioral)
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:
- "real exposure": oral presentation to a panel of examiners
- "virtual reality" : oral presentation to virtual examiners
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.
干预措施: EEG recording (Other)
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.
干预措施: In vivo social exposure (Behavioral)
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.
干预措施: EEG recording (Other)
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.
干预措施: Psychometric evaluation (Diagnostic Test)
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.
干预措施: Visual Analogue Scale of anxiety (Diagnostic Test)
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:
- "real exposure": oral presentation to a panel of examiners
- "virtual reality" : oral presentation to virtual examiners
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.
干预措施: Social exposure in a virtual reality setting (Behavioral)
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:
- "real exposure": oral presentation to a panel of examiners
- "virtual reality" : oral presentation to virtual examiners
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.
干预措施: Psychometric evaluation (Diagnostic Test)
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:
- "real exposure": oral presentation to a panel of examiners
- "virtual reality" : oral presentation to virtual examiners
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.
干预措施: Visual Analogue Scale of anxiety (Diagnostic Test)
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:
- "virtual reality" : oral presentation to virtual examiners
- "real exposure": oral presentation to a panel of examiners
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.
干预措施: In vivo social exposure (Behavioral)
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:
- "virtual reality" : oral presentation to virtual examiners
- "real exposure": oral presentation to a panel of examiners
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.
干预措施: Social exposure in a virtual reality setting (Behavioral)
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:
- "virtual reality" : oral presentation to virtual examiners
- "real exposure": oral presentation to a panel of examiners
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.
干预措施: EEG recording (Other)
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:
- "virtual reality" : oral presentation to virtual examiners
- "real exposure": oral presentation to a panel of examiners
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.
干预措施: Psychometric evaluation (Diagnostic Test)
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:
- "virtual reality" : oral presentation to virtual examiners
- "real exposure": oral presentation to a panel of examiners
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.
干预措施: Visual Analogue Scale of anxiety (Diagnostic Test)
结局指标
主要结局
Change in power of slow oscillations in prefrontal EEG recordings during anticipation relative to baseline
时间窗: 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.
次要结局
- Duration of prefrontal slow oscillations epochs during anticipation(During the 5 minutes before oral presentation)