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 obsessivecompulsive 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 (RSFC) 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 fMRI. Between scan sessions, participants with OCD received 12 weeks of sertraline. For each scan, we conducted seed-based whole-brain RSFC analyses with 6 striatal seeds. Analysis of variance (ANOVA) 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 x time effects in the OCD group showed increased striatal connectivity from baseline to 12 weeks compared with controls. Circuits demonstrating this pattern included right putamen with left frontal cortex/insula and left putamen with left frontal cortex and pre-and post-central cortices. Increase in connectivity in left putamen circuit was significantly correlated with clinical improvement on Children's Yale-Brown Obsessive-Compulsive Scale (r = −0.58, p = .03). Conclusion: Sertraline appears to affect specific striatal-based circuits in pediatric OCD, and in part, these changes may account for clinical improvement. Future work is needed to confirm these

Effects of short‐term cognitive‐coping therapy on resting‐state brain function in obsessive‐compulsive disorder

“…Citalopram primarily reduces connectivity with the sensorimotor network and structures that are related to self‐referential mechanisms (Klaassens et al., 2017). Bernstein et al report that sertraline has effects on resting‐state functional connectivity in OCD, demonstrating increased striatal connectivity from baseline to 12 weeks compared with controls including the right putamen with the left frontal cortex and insula and the left putamen with the left frontal cortex and pre‐ and postcentral cortices (Bernstein et al., 2019). In the present study, no different cluster based on ALFF was found in patients with pharmacotherapy, which might be related to the fact that 75% of the patients were taking SSRIs when they entered the clinical trial.…”

Visuomotor Activation of Inhibition-Processing in Pediatric Obsessive Compulsive Disorder: A Magnetoencephalography Study

“…A major strength of the current study is that investigation of a medication-naïve sample ensured that reported results are not driven or confounded by the effects of pharmacotherapeutic intervention on brain response (Bernstein et al, 2019). However, due to the challenge of recruiting medication-naïve participants at a tertiary care centre resulting in the small sample examined here, interpretation of our results must take into account the potential for inflated false positives in a small exploratory example.…”

“…However, magnetoencephalography (MEG) may offer some advantages over fMRI as it records neuromagnetic activity and enables tracking of neural activation with high spatial and temporal resolution (Ahlfors and Mody, 2019). Additionally, MEG can characterize the frequencies in which large groups of neurons fire during a particular task, including oscillations in the: delta (0.5-3 Hz), theta (4-7 Hz), alpha (8)(9)(10)(11)(12), beta (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29), and gamma (30+ Hz) bandwidths (Todd et al, 2014). Thus far, very few studies have used MEG to study neural response in OCD.…”

“…Studies have thus far included both medicated and un-medicated children and youth with OCD. However, medication exposure may be an important confound for consideration given recent findings that selective serotonin reuptake inhibitors (SSRIs), commonly prescribed for treatment of OCD may have effects on brain structure, function, and neurochemistry (Bernstein et al, 2019; Boedhoe et al, 2017). SSRIs have also been associated with brain change in children undertaking medication treatment targeting anxiety symptoms (Gaffrey et al, 2013).…”

Structural neural markers of response to cognitive behavioral therapy in pediatric obsessive‐compulsive disorder

“…The current study had several strengths. First, our OCD sample was free of psychotropic medications at the MRI scan, which is important given the effects of SSRIs on brain structure and connectivity (e.g., Bernstein et al, 2018;Lugo-Candelas et al, 2018). Second, this study used high-resolution data and the most up-to-date analysis methods (FreeSurfer v6.0 and MRtrix3), allowing for improved data quality and segmentation/parcellation.…”