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

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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

Original languageEnglish (US)
Pages (from-to)486-495
Number of pages10
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Volume58
Issue number5
DOIs
StatePublished - Jan 1 2019

Fingerprint

Corpus Striatum
Sertraline
Obsessive-Compulsive Disorder
Putamen
Frontal Lobe
Pediatrics
Seeds
Serotonin Uptake Inhibitors
Brain
Analysis of Variance
Therapeutics
Magnetic Resonance Imaging
Clinical Trials

Keywords

  • functional magnetic resonance imaging
  • neuroimaging
  • obsessive-compulsive disorder
  • selective serotonin reuptake inhibitors

PubMed: MeSH publication types

  • Journal Article

Cite this

@article{11612ed55db8431785890b44cb78f6c7,
title = "Sertraline Effects on Striatal Resting-State Functional Connectivity in Youth With OCD: 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",
author = "Bernstein, {Gail A.} and Cullen, {Kathryn R.} and Harris, {Elizabeth C.} and Conelea, {Christine A.} and Zagoloff, {Alexandra D.} and Carstedt, {Patricia A.} and Lee, {Susanne S.} and Mueller, {Bryon A.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.jaac.2018.07.897",
language = "English (US)",
volume = "58",
pages = "486--495",
journal = "Journal of the American Academy of Child and Adolescent Psychiatry",
issn = "0890-8567",
publisher = "Elsevier Limited",
number = "5",

}

TY - JOUR

T1 - Sertraline Effects on Striatal Resting-State Functional Connectivity in Youth With OCD

T2 - A Pilot Study

AU - Bernstein, Gail A.

AU - Cullen, Kathryn R.

AU - Harris, Elizabeth C.

AU - Conelea, Christine A.

AU - Zagoloff, Alexandra D.

AU - Carstedt, Patricia A.

AU - Lee, Susanne S.

AU - Mueller, Bryon A.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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

AB - 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

KW - functional magnetic resonance imaging

KW - neuroimaging

KW - obsessive-compulsive disorder

KW - selective serotonin reuptake inhibitors

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