BACKGROUND Imaging research has not yet delivered reliable psychiatric biomarkers. One challenge, particularly among youth, is high comorbidity. This challenge might be met through canonical correlation analysis designed to model mutual dependencies between symptom dimensions and neural measures. We mapped the multivariate associations that intrinsic functional connectivity manifests with pediatric symptoms of anxiety, irritability, and attention-deficit/hyperactivity disorder (ADHD) as common, impactful, co-occurring problems. We evaluate the replicability of such latent dimensions in an independent sample. METHODS We obtained ratings of anxiety, irritability, and ADHD, and 10 minutes of resting-state functional magnetic resonance imaging data, from two independent cohorts. Both cohorts (discovery: n = 182; replication: n = 326) included treatment-seeking youth with anxiety disorders, with disruptive mood dysregulation disorder, with ADHD, or without psychopathology. Functional connectivity was modeled as partial correlations among 216 brain areas. Using canonical correlation analysis and independent component analysis jointly we sought maximally correlated, maximally interpretable latent dimensions of brain connectivity and clinical symptoms. RESULTS We identified seven canonical variates in the discovery and five in the replication cohort. Of these canonical variates, three exhibited similarities across datasets: two variates consistently captured shared aspects of irritability, ADHD, and anxiety, while the third was specific to anxiety. Across cohorts, canonical variates did not relate to specific resting-state networks but comprised edges interconnecting established networks within and across both hemispheres. CONCLUSIONS Findings revealed two replicable types of clinical variates, one related to multiple symptom dimensions and a second relatively specific to anxiety. Both types involved a multitude of broadly distributed, weak brain connections as opposed to strong connections encompassing known resting-state networks.

中文翻译：

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共享和焦虑特定的儿科精神病理学维度表现出分布式神经相关性


背景影像学研究尚未提供可靠的精神生物标志物。一项挑战，特别是在年轻人中，是高合并症。这一挑战可以通过典型相关分析来解决，该分析旨在模拟症状维度和神经测量之间的相互依赖性。我们将内在功能连接与焦虑、易怒和注意力缺陷/多动障碍 (ADHD) 等儿科症状表现出的多变量关联绘制为常见、有影响、同时发生的问题。我们在独立样本中评估了此类潜在维度的可复制性。方法 我们从两个独立队列中获得了焦虑、易怒和 ADHD 的评分，以及 10 分钟的静息态功能磁共振成像数据。两个队列（发现：n = 182；重复：n = 326）都包括患有焦虑症、破坏性情绪失调症、注意力缺陷多动症或无精神病理学的寻求治疗的青少年。功能连接被建模为 216 个大脑区域之间的部分相关性。联合使用典型相关分析和独立成分分析，我们寻求大脑连接和临床症状的最大相关性、最大可解释的潜在维度。结果我们在发现中确定了七个典型变量，在复制队列中确定了五个典型变量。在这些典型变量中，三个变量在数据集中表现出相似性：两个变量始终捕捉到烦躁、多动症和焦虑的共同方面，而第三个变量则针对焦虑。在队列中，典型变量与特定的静息状态网络无关，而是由连接两个半球内部和跨半球的已建立网络的边缘组成。 结论 研究结果揭示了两种可复制的临床变量，一种与多种症状维度相关，另一种与焦虑相关。这两种类型都涉及大量广泛分布的弱大脑连接，而不是包含已知静息态网络的强连接。