Clinical trial NCT02631785: Fear Conditioning, Extinction and Its Recall in Anxious Youth
Official title: Fear Conditioning, Extinction and Its Recall in Anxious Youth: Identifying Neuro- Cognitive Abnormalities and Their Relation to Pediatric Anxiety Treatment Outcomes
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Pediatric Anxiety Disorders
Keywords: ANXIETY
CBT
fMRI
Fear conditioning
Fear extinction
Lead sponsor: University of Haifa
Sponsor class: OTHER
Collaborators: name: HaEmek Medical Center, Israel
name: Weizmann Institute of Science
First posted: 2015-12-16
Enrollment: 60
Sex: ALL
Minimum age (years): 8
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL

Brief summary: The proposed research aims to isolate brain-based information-processing mechanisms implicated in perturbed fear learning and extinction characteristic of pediatric anxiety.

The study will focus on the therapeutic relevance of dysfunction in fear learning and extinction for treatment by examining the associations between brain functioning and response to exposure intervention in anxious children.

Detailed description: Anxiety disorders are the most common form of pediatric psychopathology, affecting 5 - 20% of children and adolescents. Despite therapeutic advances, treatment-resistance remains high, and progress towards early detection of at-risk populations and more effective treatments has stalled. Although some anxiety disorders are transient, recent studies suggest that pediatric anxiety disorders commonly persist into adulthood. Because anxiety disorders are costly and debilitating conditions that are very often associated with other severe psychopathology such as substance abuse, depression and suicidality, there is an imperative need to identify risk and resilience factors that moderate pediatric anxiety and improve treatment.

Fear conditioning and resistance to extinction are two domains that have been implicated in the etiology and maintenance of anxiety disorders. Indeed, one of the most effective treatment for pediatric and adult anxiety disorders, exposure therapy, relies profoundly on extinction learning. The proposed research plan will investigate the neural correlates of aberrant fear conditioning and extinction processes in children and adolescents with anxiety disorders.

The proposed research aims to isolate brain-based information-processing mechanisms implicated in perturbed fear learning and extinction characteristic of pediatric anxiety. A fMRI study using a novel age-appropriate fear conditioning-extinction paradigm are proposed. The study will delineate perturbed psychological and psychophysiological response to fear conditioning and isolate neuro-cognitive mechanisms mediating extinction recall in anxious and non-anxious children. Three weeks after completing fear conditioning and extinction task in the psychophysiology lab, participants will return to complete an fMRI extinction-recall task quantifying responses to extinguished CS blends. Two major hypotheses will be examined: a) anxious children will exhibit perturbations during extinction as measured by psychophysiology indexes and self-reported fear compared to non-anxious children; b) less activation in ventromedial prefrontal cortex (vmPFC) is expected in anxious, relative to healthy, children during extinction-recall. Furthermore, the study will focus on the therapeutic relevance of dysfunction in fear learning and extinction for treatment by examining the associations between vmPFC function and response to exposure intervention in anxious children. Lower levels of vmPFC activation prior to exposure therapy and larger pre-to-post-treatment changes in vmPFC activity are expected to be associated with better response to exposure therapy.

Eligibility criteria: Research Group:

Inclusion Criteria:

* diagnosis of Separation Anxiety Disorder, Social Phobia or Generalized Anxiety Disorder.

Exclusion Criteria:

* other psychiatry diagnose (not include depression and ADHD)
* currently in psychological treatment
* psychiatry medication

Control group:

Inclusion Criteria:

healthy volunteers

Exclusion Criteria:

* any psychiatry diagnose.
* currently in psychological treatment
* psychiatry medication

Primary outcomes:
measure: fMRI Bold signal
timeFrame: 2 years
Secondary outcomes:
measure: Autonomous measures- skin conductance response (SCR)
timeFrame: 2 years
measure: Self report of anxiety
timeFrame: 2 years
measure: Autonomous measures-Fear-Potentiated Startle
timeFrame: 2 years
measure: Anxiety symptom- SCARED
timeFrame: 2 years
measure: Anxiety symptoms- ADIS
timeFrame: 2 years
measure: Anxiety symptoms- CGI
timeFrame: 2 years
Other outcomes:
Locations:
city: Haifa
country: Israel
facility: University of Haifa
city: Rehovot
country: Israel
facility: Weizmann Institue of Science
Study officials:
References:
citation: Beesdo K, Knappe S, Pine DS. Anxiety and anxiety disorders in children and adolescents: developmental issues and implications for DSM-V. Psychiatr Clin North Am. 2009 Sep;32(3):483-524. doi: 10.1016/j.psc.2009.06.002.
citation: Shechner T, Hong M, Britton JC, Pine DS, Fox NA. Fear conditioning and extinction across development: evidence from human studies and animal models. Biol Psychol. 2014 Jul;100:1-12. doi: 10.1016/j.biopsycho.2014.04.001. Epub 2014 Apr 16.
citation: Shechner T, Britton JC, Ronkin EG, Jarcho JM, Mash JA, Michalska KJ, Leibenluft E, Pine DS. Fear conditioning and extinction in anxious and nonanxious youth and adults: examining a novel developmentally appropriate fear-conditioning task. Depress Anxiety. 2015 Apr;32(4):277-88. doi: 10.1002/da.22318. Epub 2014 Nov 27.
citation: Walkup JT, Albano AM, Piacentini J, Birmaher B, Compton SN, Sherrill JT, Ginsburg GS, Rynn MA, McCracken J, Waslick B, Iyengar S, March JS, Kendall PC. Cognitive behavioral therapy, sertraline, or a combination in childhood anxiety. N Engl J Med. 2008 Dec 25;359(26):2753-66. doi: 10.1056/NEJMoa0804633. Epub 2008 Oct 30.
citation: Britton JC, Grillon C, Lissek S, Norcross MA, Szuhany KL, Chen G, Ernst M, Nelson EE, Leibenluft E, Shechner T, Pine DS. Response to learned threat: An FMRI study in adolescent and adult anxiety. Am J Psychiatry. 2013 Oct;170(10):1195-204. doi: 10.1176/appi.ajp.2013.12050651.