M145: Structural and Resting State Neural Correlates of Pediatric Obsessive-Compulsive Symptoms in the Adolescent Brain and Cognitive Development Study

Background: Subclinical Obsessive-Compulsive symptoms (OCS) in childhood increase risk for later onset of Obsessive-Compulsive Disorder (OCD) and related impairment. Studying the neural circuits underlying subclinical OCS may facilitate the identification of neural markers of risk for later OCD as well as potential targets for novel mechanism-based interventions and prevention strategies. Yet, the neural mechanisms underlying OCS and their trajectories over development are poorly understood at present, though are hypothesized to involve differential engagement of task control circuits that underlie attentional and cognitive control processes (e.g. Maia et al., 2008). Dysfunction in these circuits and processes likely contributes to the repetitive thoughts and inappropriate actions that characterize OCS. While a growing literature has probed the neural underpinnings of OCD in children, including ENIGMA mega-analytic findings suggesting larger thalamic volumes in pediatric OCD (Boedhoe et al., 2017), few studies have examined subclinical OCS. One relatively larger study noted associations between OCS and altered gray and white matter volume in healthy children (Suñol et a., 2018). The Adolescent Brain and Cognitive Development (ABCD) provides an opportunity to examine associations between OCS and brain structure in the largest sample of children to date as well as to provide novel insight into associations with resting state connectivity of task control circuits. Methods: Data from the 2.0.1 release (July 2019) of baseline data from the ABCD Study were examined. These data include clinical interviews, cognitive testing, questionnaires, and MRI assessments from a nationally representative sample of N = 11,876 9-10-year-old children. An 8-item subscale for OCS severity (Hudziak et al., 2006) was ascertained from parent report on the Child Behavior Checklist (CBCL). Diagnosis of OCD was based on parent report on the Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Age Children (KSADS). Cognitive performance was assessed using the NIH Toolbox. Of these children, n = 10,585 successfully completed T1 structural imaging that were analyzed using FreeSurfer and that passed ABCD quality control procedures. Resting state data was also collected and analyzed with the ABCD pipelines; n = 8,341 children had >5 minutes of data retained after quality control. Within and between network connectivity was extracted from regions/networks defined in the Gordon et al., 2016 atlas. Linear mixed effects models were used to examine whether CBCL OCS related to cognitive performance, subcortical volumes, cortical thickness, or resting state connectivity of default mode and task control circuits. Results: N = 5,257 children (44.30%) exhibited non-zero CBCL OCS scores and, as expected, scores were elevated among the N = 898 children who met KSADS criteria for current OCD (b = 2.30, t = 36.82, p −2.79, p

背景：儿童期亚临床强迫症症状（Subclinical Obsessive-Compulsive Symptoms，OCS）会增加后续强迫症（Obsessive-Compulsive Disorder，OCD）发病及相关功能损害的风险。研究亚临床OCS背后的神经环路，或许有助于识别后续OCD发病风险的神经标志物，以及为基于新机制的干预措施和预防策略提供潜在靶点。然而，目前对OCS背后的神经机制及其在发育过程中的轨迹仍知之甚少，不过假设其涉及注意力和认知控制过程所依赖的任务控制环路的差异性激活（如Maia等人，2008年所述）。这些环路和过程的功能障碍可能导致OCS特有的重复思维和不当行为。尽管越来越多的文献探讨了儿童OCD的神经基础，包括ENIGMA mega分析结果显示儿童OCD患者丘脑体积更大（Boedhoe等人，2017年），但针对亚临床OCS的研究却很少。一项规模相对较大的研究指出，健康儿童中OCS与灰白质体积改变存在关联（Suñol等人，2018年）。青少年大脑认知发展研究（Adolescent Brain and Cognitive Development，ABCD）为在迄今为止最大的儿童样本中探讨OCS与脑结构的关联，以及深入了解其与任务控制环路静息态连接的关系提供了机会。

方法：本研究分析了ABCD研究2019年7月发布的2.0.1版本基线数据。这些数据涵盖了全国代表性样本中11876名9-10岁儿童的临床访谈、认知测试、问卷和MRI评估结果。OCS严重程度的8项子量表（Hudziak等人，2006年）由家长填写的儿童行为量表（Child Behavior Checklist，CBCL）报告确定。OCD诊断基于家长填写的学龄儿童情感障碍和精神分裂症评定量表（Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Age Children，KSADS）报告。认知表现通过NIH Toolbox进行评估。其中10585名儿童成功完成了T1结构成像，这些成像数据通过了ABCD质量控制流程，并使用FreeSurfer进行分析。同时收集了静息态数据，并使用ABCD数据处理流程进行分析；8341名儿童的静息态数据在质量控制后保留了超过5分钟的有效时长。网络内和网络间连接数据从Gordon等人2016年提出的脑图谱所定义的脑区/网络中提取。研究采用线性混合效应模型（Linear Mixed Effects Models）探讨CBCL OCS与认知表现、皮层下体积、皮层厚度以及默认模式和任务控制环路静息态连接之间的关系。

结果：5257名儿童（44.30%）的CBCL OCS得分非零，且正如预期，在符合KSADS当前OCD诊断标准的898名儿童中，得分显著升高（b=2.30，t=36.82，p<.001）。