Developmental Trajectories of Brain Network Strength and Flexibility: Relationship to Risk, Onset and Course of Depression and Self-Harm in Youth

摘要 抑郁症、非自杀性自伤（NSSI）和自杀想法和行为（STB）通常出现在 青少年和每一个都是自杀死亡的重要危险因素。早期发现和干预， 承诺改变轨迹，改善成人结果和预防自杀。大脑网络与 抑郁症（额叶-边缘系统威胁，皮质-纹状体途径/奖励和默认模式）经历了显着的 在童年和青春期的变化;这些变化如何展开的方式可能是至关重要的， 了解抑郁症、NSSI和STB的发病和病程。青少年大脑认知 发展（ABCD）是一项基于人群的研究，每年跟踪超过11，000名儿童， 这些数据已经公开，前三年的临床和神经影像学数据已经公开。自从ABCD 数据收集跨越了一个关键的发展窗口，值得注意的是抑郁症，NSSI和 STB，分析这些数据提供了一个理想的机会来表征神经网络之间的联系， 变化和青少年自杀的风险。静息态功能磁共振成像（rs-fMRI）可用于表征大脑 网络结构和组织。虽然我们的实验室和其他实验室已经广泛应用了标准 功能连接方法，以表征强度内抑郁症网络使用横截面 设计，需要纵向设计来了解现在网络强度的异常发展可能 有助于抑郁症发作，NSSI和STB。最近，出现了新的方法来估计 rsfMRI数据的网络灵活性。这些方法包括从信息论中提取信息， 大脑信号和动态连接分析来测量状态转换，或大脑之间的转换 休息期间的网络配置。我们的初步数据表明，大脑灵活性与 （熵和状态转换频率）和抑郁症，NSSI和STB在青少年，这表明一个潜在的 陷入消极思维和感受的神经机制。我们建议， 儿童时期神经网络强度和灵活性变化轨迹的差异， 青春期可能有助于解释青少年抑郁症和自杀风险的出现。在我们的概念 模型、遗传和环境因素塑造了网络发展轨迹，而网络发展轨迹反过来又构成了 抑郁症、NSSI和STB的出现。这项建议旨在描绘神经发育 额-边缘威胁、皮质-纹状体途径/奖励和默认模式下的力量和灵活性轨迹 与儿童抑郁症、NSSI和STB的风险、发作和早期病程相关的网络， 青少年在ABCD研究中使用新的分析策略。这项研究的新见解将提供 设计个性化干预措施以促进早期发现抑郁症和自杀风险的基础， 并指导能够恢复健康大脑发育和避免严重负面影响的干预措施， 结果包括自杀。

Abstract Depression, non-suicidal self-injury (NSSI) and suicidal thoughts and behaviors (STB) commonly emerge in youth and each represent important risk factors for death by suicide. Early detection and intervention has the promise of altering trajectories, improving adult outcomes and preventing suicide. Brain networks implicated in depression (frontal-limbic threat, cortico-striatal approach/reward and default mode) undergo significant change during childhood and adolescence; the manner of how these changes unfold may be critical to understanding the onset and course of depression, NSSI, and STB. The Adolescent Brain Cognitive Development (ABCD) is a population-based study that is following over 11,000 children annually over 10 years, with clinical and neuroimaging data from the first three years already publicly available. Since ABCD data collection spans a critical developmental window notable for significant rises in depression, NSSI and STB, analyzing this data presents an ideal opportunity to characterize the links between neural network changes and unfolding risk for suicide in youth. Resting-state fMRI (rs-fMRI) can be used to characterize brain network structure and organization. While our laboratory and others have extensively applied standard functional connectivity methods to characterize strength within depression networks using cross-sectional designs, longitudinal designs are needed to understand now aberrant development in network strength may contribute to onset depression, NSSI and STB. Recently, novel approaches have emerged to estimate network flexibility from rsfMRI data. These include drawing from information theory to measure entropy of brain signals and from dynamic connectivity analyses to measure state-switching, or shifts between brain network configurations during rest. Our preliminary data point to inverse relationships between brain flexibility (entropy and state-switching frequency) and depression, NSSI and STB in adolescents, suggesting a potential neural mechanism for getting “stuck” in negative ways of thinking and feeling. We propose that individual differences in the trajectory of neural network strength and flexibility changes across childhood and adolescence may help explain the emergence of depression and suicide risk in adolescents. In our conceptual model, inherited and environmental factors shape network developmental trajectories, which in turn underlie the emergence of depression, NSSI and STB. This proposal seeks to delineate the neurodevelopmental trajectories of strength and flexibility in fronto-limbic threat, cortico-striatal approach/reward and default mode networks associated with the risk, onset and early course of depression, NSSI and STB in children and adolescents in the ABCD study using novel analytic strategies. New insights from this study will provide the foundation for designing personalized interventions to facilitate early detection of depression and suicide risk, and to guide interventions capable of restoring healthy brain development and averting serious negative outcomes including suicide.