University of Minnesota, Minneapolis.
University of Minnesota, Minneapolis.
J Am Acad Child Adolesc Psychiatry. 2019 May;58(5):486-495. doi: 10.1016/j.jaac.2018.07.897. Epub 2018 Oct 30.
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.
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.
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).
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.
Effects of Sertraline on Brain Connectivity in Adolescents with OCD; https://clinicaltrials.gov/; NCT02797808.
需要了解儿童强迫症（OCD）神经回路的基础知识及其在标准治疗过程中的变化，为新概念和新型靶向治疗的发展提供依据。本研究探讨了选择性 5-羟色胺再摄取抑制剂舍曲林对儿童 OCD 皮质-纹状体-丘脑-皮质回路静息态功能连接的影响。
无药物治疗的 OCD 青少年（n=14）和健康对照者（n=14）分别在基线和 12 周时接受静息态功能磁共振成像检查。扫描期间，OCD 患者接受 12 周舍曲林治疗。对于每个扫描，使用 6 个纹状体种子进行基于种子的全脑静息态功能连接分析。方差分析检验了组间和时间对纹状体连接的交互作用，包括基于聚类的阈值校正多重检验。通过对组间分析确定的回路内的连接变化与临床变化进行相关性分析。
OCD 组有 2 个显著的组间时间效应，与对照组相比，12 周时纹状体连接增加。表现出这种模式的回路包括右侧壳核与左侧额叶皮层和岛叶，以及左侧壳核与左侧额叶皮层和额、顶、后中央皮层。左侧壳核回路连接的增加与儿童耶鲁-布朗强迫症量表评分的临床改善显著相关（r=-0.58，p=0.03）。
舍曲林似乎影响了儿童 OCD 中特定的基于纹状体的回路，这些变化部分可以解释临床改善。需要进一步的研究来确认这些初步发现，这将有助于确定基于回路的新型治疗靶点。
舍曲林对强迫症青少年大脑连接的影响；https://clinicaltrials.gov/；NCT02797808。
