Clinical trial NCT04685018: The Neurocircuitry of Relief During Avoidance Learning in Patients With Obsessive-compulsive Disorder
Official title: The Neurocircuitry of Relief During Avoidance Learning in Patients With Obsessive-compulsive Disorder
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Obsessive-Compulsive Disorder
Keywords: Avoidance behavior
Reward
Conditioning
Extinction
Anxiety Disorders
OCD
fMRI
Lead sponsor: KU Leuven
Sponsor class: OTHER
First posted: 2020-12-28
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Healthy group: Mentally and medically healthy adults between 18 and 60 years, free from any current or previous medical or psychiatric condition.

OCD group: Same as the healthy group, except for the diagnosis of OCD and medication-free or with a stable medication regimen for at least 3 weeks prior to the study.

Brief summary: To investigate the neuro-mechanisms underpinning persistent avoidance in OCD patients

Detailed description: Many compulsions displayed by obsessive-compulsive disorder (OCD) patients serve to protect against perceived threat and can, therefore, be conceptualized as 'avoidance responses'. Exposure treatment with response prevention (ET+RP) is aimed at exposing patients to their obsessive thoughts and perceived threats while preventing engagement in compulsive avoidant responses. This induces extinction of threat perception and fearful arousal and hence reduces the motivation to avoid. While successful in many patients, however, as much as 40% dropout during treatment or display persistent avoidance after ET+RP. There is a clear need for treatment improvement for these often highly disabled patients.

Improving ET+RP outcomes requires a deeper understanding of the mechanisms that drive excessive and persistent avoidance in OCD patients. Psychological theories ascribe an important role to the relief that follows avoidance when the anticipated threat is successfully averted. This positive feeling arguably functions as a reward to reinforce the foregoing avoidance actions. Indeed, fMRI studies have found that the neurocircuitry of relief overlaps with that of reward, including the ventral tegmental area, ventral striatum and orbitofrontal cortex. Here, the authors will test the hypothesis that excessive-persistent avoidance is linked to exaggerated activation of the relief circuitry in OCD patients. For that purpose, we will acquire functional brain images of OCD patients in an MRI scanner and compare to healthy participants, while they participate in a computer task that is designed to model avoidance learning and relief.

Eligibility criteria: Inclusion Criteria:

* Healthy volunteers 18-60 years old;
* Participants are motivated and give written informed consent;
* Adequate demand of Dutch language;
* Subjects have never participated in a fear conditioning task;
* Diagnosis of OCD (for OCD group only);
* Contraindications for the MRI exam.

Exclusion Criteria:

* Current neurological (e.g. Epilepsia), respiratory, cardiovascular, metabolic, gastrointestinal, endocrine (especially diabetes), renal or urinary diseases, psychiatric disorder or other relevant medical histories (except for OCD in the OCD group);
* Being pregnant or lactating;
* Alcohol intake greater than 14 alcoholic units per week (one alcoholic unit = 10 gr ethanol);
* History of cannabis use or any other drug of abuse during the 3 months prior to the study;
* The medical doctor has asked to the participant to stay away from stressful situations;
* Electronic implants (e.g., pacemaker);
* Pain or other condition of the hand or the wrist.

Primary outcomes:
measure: Avoidance responses during the avoidance-relief task
timeFrame: 1 hour for avoidance task
measure: Relief during the omissions of the US
timeFrame: 1 hour to perform the avoidance task
Secondary outcomes:
measure: Tolerance to stress
timeFrame: 1 hour to perform the avoidance task
measure: Therapeutic outcome in OCD
timeFrame: 1 hour to perform the avoidance task
measure: Resting-state connectivity
timeFrame: 1 hour to perform the avoidance task
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: Psychiatry | UZ Leuven campus Gasthuisberg
Study officials:
References:
citation: Vervliet B, Lange I, Milad MR. Temporal dynamics of relief in avoidance conditioning and fear extinction: Experimental validation and clinical relevance. Behav Res Ther. 2017 Sep;96:66-78. doi: 10.1016/j.brat.2017.04.011. Epub 2017 Apr 23.
citation: Milad MR, Furtak SC, Greenberg JL, Keshaviah A, Im JJ, Falkenstein MJ, Jenike M, Rauch SL, Wilhelm S. Deficits in conditioned fear extinction in obsessive-compulsive disorder and neurobiological changes in the fear circuit. JAMA Psychiatry. 2013 Jun;70(6):608-18; quiz 554. doi: 10.1001/jamapsychiatry.2013.914.
citation: Leknes S, Lee M, Berna C, Andersson J, Tracey I. Relief as a reward: hedonic and neural responses to safety from pain. PLoS One. 2011 Apr 7;6(4):e17870. doi: 10.1371/journal.pone.0017870.
citation: Gillan CM, Morein-Zamir S, Urcelay GP, Sule A, Voon V, Apergis-Schoute AM, Fineberg NA, Sahakian BJ, Robbins TW. Enhanced avoidance habits in obsessive-compulsive disorder. Biol Psychiatry. 2014 Apr 15;75(8):631-8. doi: 10.1016/j.biopsych.2013.02.002. Epub 2013 Mar 16.