Sertraline Effects on Striatal Resting-State Functional Connectivity in Youth With Obsessive-Compulsive Disorder: A Pilot Study

Abstract

Objective: Foundational knowledge on neural circuitry underlying pediatric obsessive-compulsive disorder (OCD) and how it changes during standard treatment is needed to provide the basis for conceptualization and development of novel targeted treatments. This study explored the effects of sertraline, a selective serotonin reuptake inhibitor, on resting-state functional connectivity in cortico-striatal-thalamic-cortical circuits in pediatric OCD.

Method: Medication-free youths with OCD (n = 14) and healthy controls (n = 14) were examined at baseline and 12 weeks with resting-state functional magnetic resonance imaging. Between scan sessions, participants with OCD received 12 weeks of sertraline. For each scan, seed-based whole-brain resting-state functional connectivity analyses were conducted with 6 striatal seeds. Analysis of variance examined the interaction between group and time on striatal connectivity, including cluster-based thresholding to correct for multiple tests. Connectivity changes within circuits identified in group analyses were correlated with clinical change.

Results: Two significant group-by-time effects in the OCD group showed increased striatal connectivity from baseline to 12 weeks compared with controls. Circuits demonstrating this pattern included the right putamen with the left frontal cortex and insula and the left putamen with the left frontal cortex and pre- and post-central cortices. Increase in connectivity in the left putamen circuit was significantly correlated with clinical improvement on the Children's Yale-Brown Obsessive-Compulsive Scale score (r = -0.58, p = .03).

Conclusion: Sertraline appears to affect specific striatal-based circuits in pediatric OCD, and these changes in part could account for clinical improvement. Future work is needed to confirm these preliminary findings, which would facilitate identification of circuit-based targets for novel treatment development.

Clinical trial registration information: Effects of Sertraline on Brain Connectivity in Adolescents with OCD; https://clinicaltrials.gov/; NCT02797808.

Keywords: functional magnetic resonance imaging; neuroimaging; obsessive-compulsive disorder; selective serotonin reuptake inhibitors.

Figure 1:

Consort Diagram Note: DNQ = did not qualify; MRI = magnetic resonance imaging; OCD = obsessive-compulsive disorder; SBNE = screened but not enrolled. ^a Includes 65 controls who were screened but not scheduled ^b One participant’s data excluded because data were acquired on different scanner ^c One participant’s week 12 data excluded due to motion artifact

Figure 2:

Significant Clusters from the Two-Way Mixed Effects Analysis of Variance (ANOVA) Note: Coordinates represent the location of the slices displayed. Top row: results from right putamen cluster with maximum z-score of 3.85 located at x = −40, y = −30, z = 30. Bottom row: results from left putamen cluster with maximum z-score of 4.6 located at x = −40, y = −34, z = 28.

Figure 3:

Boxplots of Connectivity Z-Scores for Right Putamen and Left Putamen at Baseline and 12 Weeks for Obsessive-Compulsive Disorder (OCD) and Control Groups

Figure 4:

Change in Left Putamen Connectivity Z-Scores (Baseline to Week 12) Correlated with Change in Children’s Yale-Brown Obsessive Compulsive Scale (CY-BOCS) Total Scores (Baseline to Week 12)