Threat-Avoidance Learning in Anxiety Patients (AVOID)

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

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.

Study Overview

• Status: Unknown
• Conditions: Stress Disorders, Traumatic; Phobic Disorders; Panic Disorder
• Intervention / Treatment: Behavioral: Avoidance experiment

• Study Type: Observational
• Enrollment (Anticipated): 80

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • University of KU Leuven

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Healthy Controls, Panic Disorder, Phobic Disorders, Post-Traumatic Stress Disorder

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy Control Group; Volunteers that meet no diagnostic criteria for mental disorders.	Behavioral: Avoidance experiment; Participants complete an avoidance task
Panic Disorder Group; Volunteers that meet diagnostic criteria for Panic Disorder.	Behavioral: Avoidance experiment; Participants complete an avoidance task
Phobic Disorder Group; Volunteers that meet diagnostic criteria for a Phobic Disorder.	Behavioral: Avoidance experiment; Participants complete an avoidance task
PTSD group; Volunteers that meet diagnostic criteria for Post-Traumatic Stress Disorder	Behavioral: Avoidance experiment; Participants complete an avoidance task

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: KU Leuven
• Collaborators: European Commission
• Investigators: Principal Investigator: Dirk Hermans, Prof., University of KU Leuven

Publications and helpful links

General Publications

• Milad MR, Pitman RK, Ellis CB, Gold AL, Shin LM, Lasko NB, Zeidan MA, Handwerger K, Orr SP, Rauch SL. Neurobiological basis of failure to recall extinction memory in posttraumatic stress disorder. Biol Psychiatry. 2009 Dec 15;66(12):1075-82. doi: 10.1016/j.biopsych.2009.06.026. Epub 2009 Sep 12.
• Milad MR, Quirk GJ. Fear extinction as a model for translational neuroscience: ten years of progress. Annu Rev Psychol. 2012;63:129-51. doi: 10.1146/annurev.psych.121208.131631.

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Anticipated): March 1, 2017
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: January 8, 2015
• First Submitted That Met QC Criteria: January 8, 2015
• First Posted (Estimate): January 13, 2015

Study Record Updates

• Last Update Posted (Estimate): February 6, 2015
• Last Update Submitted That Met QC Criteria: February 5, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: Anxiety; Fear; Avoidance
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Anxiety Disorders; Trauma and Stressor Related Disorders; Disease; Stress Disorders, Traumatic; Panic Disorder; Phobic Disorders
• Other Study ID Numbers: bramvervliet