Fear Conditioned Response in Healthy Subjects and in OCD Patients Pre and Post Treatment With Sertraline.
Condition: Obsessive-Compulsive Disorder
MeSH terms: Compulsive Personality Disorder; Obsessive-Compulsive Disorder
Study type: Interventional
Phase: Phase 4

Summary: 
      24 OCD patients and 24 healthy subjects will be submitted to a two-day fear conditioning
      paradigm during acquisition of functional magnetic resonance imaging (fMRI). OCD patients
      will be submitted to the paradigm at two timepoints: baseline and 4 weeks after treatment
      initiation with sertraline up to 200mg/day or maximum tolerated dosage. OCD patients are
      expected to demonstrate worsened extinction retention compared to healthy subjects at
      baseline. Sertraline treatment is expected to improve extinction retention compared to
      baseline and to normalize the brain regions being recruited with the conditioned stimuli
      presented during the recall phase.
    

Detailed description: 
      Fear conditioning paradigms are used to investigate the learning process of the fear response
      in patients with psychiatric disorders and healthy subjects. Patients with post traumatic
      stress disorder have been shown to fail to retrieve the memory of fear extinction during the
      recall phase of the fear conditioning paradigm when compared to healthy subjects. In one
      previous trial, obsessive-compulsive disorder (OCD) patients have demonstrated the same
      failure to recall extinction and the results from functional magnetic resonance imaging
      (fMRI) activation maps have shown different regions being recruited during recall when
      compared with healthy subjects. However, in that previous trial, some of the OCD patients
      included were already taking medication for OCD. In the current trial, we will evaluate 24
      unmedicated OCD patients with a two-day fear conditioning paradigm before and after 4-weeks
      of treatment initiation with sertraline up to 200mg/day or maximum tolerated dosage.
      Sertraline is a first-line treatment option for OCD. At baseline, OCD patients will be
      compared to 24 healthy subjects. At post treatment, fear conditioning and fMRI results wil be
      compared to baseline. OCD patients are expected to demonstrate worsened extinction retention
      compared to healthy subjects at baseline. Sertraline treatment is expected to improve
      extinction retention compared to baseline and to normalize the brain regions being recruited
      with the conditioned stimuli presented during the recall phase. By "normalize" we mean that
      after treatment the regions being recruited will be the same as the ones recruited by healthy
      subjects during baseline, in other words, differences found at baseline regarding brain
      activation by the conditioned stimuli are expected to disappear after treatment.

      Abbreviations: CS= conditioned stimuli, CS+= conditioned stimuli to shock, CS-=neutral
      conditioned stimuli, CS+E= extinguished conditioned stimuli to shock, CS+U=unextinguished
      conditioned stimuli to shock
    

Intervention name(s): Sertraline Hydrochloride
Intervention type(s): Drug
Intervention description(s): first week: sertraline hydrochloride 50mg/day, second week: sertraline hydrochloride 100mg/day, third week: sertraline hydrochloride 150mg/day, fourth week: sertraline hydrochloride 200mg/day OBS.: Other SSRIs (fluoxetine, paroxetine, escitalopram) with equivalent dosage schedules can be used if patients report prior intolerance to sertraline
Other intervention name(s): sertraline 50mg; zoloft
Intervention MeSH terms: Sertraline
Intervention model: Single Group Assignment
Intervention model description: 4-weeks open label trial of sertraline up to 200mg/day treatment for obsessive compulsive disorder
Masking: None (Open Label)
Primary purpose: Other
Keywords: obsessive-compulsive disorder; fear conditioning; functional neuroimaging; sertraline