Effects of Sertraline on Brain Connectivity in Adolescents With OCD

Study Overview
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Brief Summary
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The investigators will examine how treatment with sertraline for 12 weeks impacts frontal-striatal-thalamic circuitry (FSTC) in this OCD sample.

Detailed Description
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To examine FSTC using advanced multi-modal imaging techniques, including resting-state functional magnetic resonance imaging (R-fMRI) and high angular resolution diffusion imaging (HARDI), in 25 medication-free adolescents youths with OCD (ages 8-17) in comparison with 25 matched healthy controls. Hypotheses: (A) Based on the pilot data, adolescents youths with OCD will show lower functional connectivity in FSTC at baseline when compared with controls, and , lower functional connectivity in FSTC will correlate with greater severity on CY-BOCS. (B) Adolescents Youths with OCD will also show abnormalities in structural connectivity in FSTC at baseline when compared with controls, and structural and functional connectivity will be related. (C) The investigators will explore relations between OCD dimensions and functional connectivity measures, and predict that the repeating/ordering dimension will correlate with orbitofrontal cortex (OFC) connections, hoarding will correlate with rostral anterior cingulate cortex (ACC) connections, and forbidden thoughts will correlate with caudal ACC connections. To investigate how sertraline impacts functional connectivity in FSTC in adolescents with OCD. Hypothesis: After 12 weeks of sertraline treatment, functional connectivity measures within FSTC for the OCD group will (on average) increase compared to baseline and will no longer be significantly different when compared with controls. Non-responders may show a different pattern (i.e. failure to show these changes).

Official Title
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Effects of Sertraline on Brain Connectivity in Adolescents With OCD (Obsessive-Compulsive Disorder)

Conditions
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OCD

Intervention / Treatment
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* Drug: Sertraline
* Other: No Intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (OCD): OCD as the primary Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) diagnosis based on the Anxiety Disorders Interview Schedule (ADIS) for DSM-IV, Child Version Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) score of greater than 15 Exclusion Criteria (OCD): lifetime diagnosis of bipolar disorder, schizophrenia, or substance abuse/dependence on ADIS Intelligence Quotient (IQ) < 80 on Wechsler Abbreviated Scales of Intelligence (WASI) positive urine drug screen MRI-incompatible features (e.g., metal implants, claustrophobia) current or recent trial of psychotropic medication (within the past 4 8 weeks or past 6 12 weeks for fluoxetine) non-response in > 2 selective serotonin reuptake inhibitor (SSRI) trials of adequate dose/duration positive pregnancy test history of seizure disorder or serious head injury Inclusion Criteria (Controls): Healthy 8-17 year olds Exclusion criteria (controls): No psychiatric diagnoses No immediate family history of OCD

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Children with OCD<br>Children with obsessive compulsive disorder, not currently on medication for OCD | Drug: Sertraline<br>* Impact of sertraline on functional brain connectivity<br>* Other names: Zoloft;|
| Active Comparator: Healthy Control Children<br>Children without obsessive compulsive disorder | Other: No Intervention<br>* Healthy control non-intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CY-BOCS Total Score at 12-weeks | The Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) a clinician-rated semi-structured instrument assessing OCD severity over the previous 7 days in children ages 6 to 17 years. Items are scored from 0 (none) to 4 (extreme) and total score ranges from 0 to 40 with higher scores indicating greater impairment. All 19 items are rated, but only items 1-10 are used to determine the total score. The total CY-BOCS score is the sum of items 1-10; the obsession and compulsion subtotals are the sums of items 1-5 and 6-10, respectively. At this time, items 1A and 6A are not being used in the scoring. Items 17 (global severity) and 18 (global improvement) are adapted from the Clinical Global Impression Scale to provide measures of overall functional impairment associated with the presence of obsessive-compulsive symptoms. | 12 weeks | 
| Longitudinal 2-Group Resting State Functional Conectivity (RSFC) Analyses | Participants had whole brain fMRI at baseline &12 weeks. Whole brain connectivity in 6 striatal ROIs was performed. Two-way mixed effects ANOVAs were performed with FEAT. Clusters were significant if p <.0042 based on .05/(6 ROIs x 2 tests/ROI). Mean z-score was found for each time point in each subject's connectivity map in each significant cluster. Within-group paired-sample t tests examined RSFC change over time in these metrics for each group. To investigate group X time interactions from the 2-way ANOVA, we compared mean z-scores within each significant cluster at baseline & 12 weeks. Resulting numbers represented striatal connectivity for each individual at each time point. Within group paired sample t-tests examined RSFC change over time for each group. Bonferroni correction was applied to alpha level (2-tailed, p<0.5/6 =.0083) for multiple testing. We do not have an a priori hypothesis as to whether increase or decrease in RSFC is a better outcome. Unit of measure is z-score. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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OCD