Clinical trial NCT02336802: Threat-Avoidance Learning in Anxiety Patients
Official title: The Experimental Study of Threat-Avoidance in Anxiety Patients: Behavioral, Emotional, and Neural Correlates
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Panic Disorder
Phobic Disorders
Stress Disorders, Traumatic
Keywords: Anxiety
Fear
Avoidance
Lead sponsor: KU Leuven
Sponsor class: OTHER
Collaborators: name: European Commission
First posted: 2015-01-13
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Healthy Controls, Panic Disorder, Phobic Disorders, Post-Traumatic Stress Disorder

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: functional magnetic resonance imaging
timeFrame: 1.5 hours
Secondary outcomes:
measure: Skin conductance reactivity
timeFrame: 1.5 hours
measure: Questionnaires
timeFrame: 2 hours
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: University of KU Leuven
Study officials:
affiliation: University of KU Leuven
name: Dirk Hermans, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.