Threat-Avoidance Learning in Anxiety Patients

Study Overview
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Brief Summary
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Anxiety disorders are characterized by exaggerated levels of fear that are not proportional to the actual level of threat. More specifically, anxiety patients have marked deficits in the downregulation of fear reactions during situations of objective safety. Pre-clinical research on Pavlovian fear conditioning and extinction has discovered that fear downregulation stems from areas in the prefrontal cortex (the ventro-medial prefrontal cortex, vmPFC) that recruit intercalated cells in the amygdala to inhibit its central nucleus, which is responsible for a variety of behavioral expressions of fear (Milad & Quirk, 2012). Accordingly, functional magnetic resonance imaging studies (fMRI) revealed reduced vmPFC activity coupled with increased fear reactions during situations of objective safety in anxiety patients (Milad et al., 2009). Another core symptom of anxiety disorders, though much less investigated, is the excessive avoidance of situations that trigger the fears. These 'safety behaviors' often interfere with daily life activities and valued goals in life, and they are thought to perpetuate the exaggerated levels of fear by precluding opportunities to learn that the feared situations are actually not dangerous. Surprisingly, experimental research on avoidance behaviors in anxiety patients is virtually non-existent. This experiment modifies the Pavlovian fear conditioning procedure to include avoidance, and explores the behavioral and neural processes of this type of fear regulation in anxiety patients (trans-diagnostically) and healthy individuals.

Official Title
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The Experimental Study of Threat-Avoidance in Anxiety Patients: Behavioral, Emotional, and Neural Correlates

Conditions
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Panic Disorder, Phobic Disorders, Stress Disorders, Traumatic

Intervention / Treatment
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* Behavioral: Avoidance experiment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-65 years of age. Proficient in English. Right-handed Free of medication that affect cerebral metabolism. Able to give informed consent. High stress level (defined as a score of >= 3 on the 4-item Perceived Stress Scale). Exclusion Criteria: History of neurologic or psychiatric disease (other than the specified anxiety disorder), substance abuse or dependence that is current or within the last year. Major/chronic medical conditions. History of head injury resulting in prolonged loss of consciousness and/or neurological sequelae. History of seizures. History of stroke Prior neurosurgical procedure. Metal in the body, metal injury to the eyes. Implanted pacemaker, medication pump, vagal stimulator, deep brain stimulator, TENS unit, or ventriculo-peritoneal shunt. Pregnancy; breastfeeding or nursing Claustrophobia Weight > 350 lbs.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy Control Group<br>Volunteers that meet no diagnostic criteria for mental disorders. | Behavioral: Avoidance experiment<br>* Participants complete an avoidance task<br>|
| Panic Disorder Group<br>Volunteers that meet diagnostic criteria for Panic Disorder. | Behavioral: Avoidance experiment<br>* Participants complete an avoidance task<br>|
| Phobic Disorder Group<br>Volunteers that meet diagnostic criteria for a Phobic Disorder. | Behavioral: Avoidance experiment<br>* Participants complete an avoidance task<br>|
| PTSD group<br>Volunteers that meet diagnostic criteria for Post-Traumatic Stress Disorder | Behavioral: Avoidance experiment<br>* Participants complete an avoidance task<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| functional magnetic resonance imaging | We will measure functional MRI during fear conditioning, avoidance and generalization. Furthermore, we will measure changes in structural MRI data, Diffusion Tensor Imaging (DTI) data and resting state fMRI data. | 1.5 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Skin conductance reactivity | fluctuations in skin conductance will be measured alongside MRI data collection, as a peripheral physiological measure of fear. | 1.5 hours | 
| Questionnaires | In a separate sessions, participants will fill out a variety of personality questionnaires probing levels of anxiety and avoidance tendency. | 2 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anxiety, Fear, Avoidance