Fear Conditioned Response in Healthy Subjects and in OCD Patients Pre and Post Treatment With Sertraline. (FEARCON)

Fear Conditioned Response in Healthy Subjects and in OCD Patients Pre and Post Treatment With Sertraline.

Fear Conditioning, Extinction and Recall in Healthy Subjects and in Obsessive-compulsive Disorder Patients Pre and Post Treatment With Sertraline.

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.

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

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

Baseline for both groups (OCD and helthy subjects), change from baseline to 4 weeks after treatment initiation only for intervention group

Baseline for both groups (OCD and helthy subjects), change from baseline to 4 weeks after treatment initiation only for intervention group

Main behavioral measure baseline comparison (extinction retention index OCD patients versus healthy subjects)

Main functional neuroimaging measure (activation maps for contrast CS+E versus CS-during recall phase,OCD patients versus healthy subjects)

Secondary Behavioral Measure (context discrimination index based on skin conductance, OCD patients pre and post treatment)

Secondary Behavioral Measure (context discrimination index based on skin conductance, OCD patients versus healthy subjects)

Secondary functional neuroimaging measure (functional activation maps for contrast CS+/CS- during conditioning phase, OCD patients pre and post treatment)

Secondary functional neuroimaging measure (functional activation maps for contrast CS+/CS- during conditioning phase, OCD patients versus healthy subjects)

Secondary functional neuroimaging measure (functional activation maps for contrast CS+E/CS- during recall phase of baseline measurement, OCD patients versus healthy subjects)

Alternative activations (OCD patients versus controls), regions other than the vmPFC, activated with CS+ presentations during recall

Secondary functional neuroimaging measure (functional activation maps for contrast CS+E/CS- during recall phase comparing change between post and pre treatment)

Alternative activations (OCD patients post treatment compared with baseline), regions other than the vmPFC, activated with CS+E presentations during recall

Inclusion Criteria: Healthy controls -willingness to participate in research OCD patients willingness to participate in research main diagnosis of OCD (psychiatric clinical evaluation) minimum YBOCS (Yale Brown Obsessive-compulsive severity scale) score of 16 points Exclusion Criteria: Healthy controls any current psychiatric diagnosis according to evaluation using semi structured interview for DSM IV diagnoses (SCID I) any past psychiatric diagnoses except single major depression episode and simple phobia (evaluation by semi structure interview-SCID I) current use of psychotropic medications (last use has to be at least 3 months prior to study initiation) chronic use of any medications except vitamins and contraceptives MRI exclusionary criteria (metal implants, recently made tatoos, claustrophobia, etc) being pregnant OCD patients comorbidity with neurodevelopmental disorders (autism, mental retardation), current psychotic disorders, current substance dependence or abuse, bipolar mood disorder according to evaluation using semi structured interview for DSM IV diagnoses (SCID I) current use of psychotropic medications (last use has to be at least 3 months prior to study initiation) MRI exclusion criteria(metal implants, recently made tatoos, claustrophobia, etc) being pregnant or at risk of becoming pregnant