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、非自杀性自我伤害(NSSI)和自杀想法和行为(STB)通常出现在 青少年和青少年都是自杀死亡的重要危险因素。及早发现和干预具有 承诺改变轨迹，改善成人结局，防止自杀。牵涉到的大脑网络 抑郁(额叶-边缘威胁、皮质-纹状体途径/奖励和默认模式)经历显著 儿童和青春期的变化；这些变化如何展开的方式可能对 了解抑郁症、NSSI和STB的发病和病程。青春期大脑认知 发展(ABCD)是一项以人口为基础的研究，每年跟踪调查11,000名10岁以上的儿童 几年来，前三年的临床和神经成像数据已经公开。自ABCD以来 数据收集跨越了一个关键的发展窗口，显著增加了抑郁症、NSSI和 STB，分析这些数据提供了一个描述神经网络之间联系的理想机会 青年时期自杀的变化和风险。静息状态fmri(rs-fmri)可以用来描述大脑的特征。 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 利用横截面表征凹陷网络内强度的功能连通性方法 设计，需要纵向设计来理解现在网络力量的异常发展可能 导致发作性抑郁症、NSSI和STB。最近，出现了新的方法来估计 来自rsfMRI数据的网络灵活性。其中包括从信息论中提取信息来测量 大脑信号和动态连通性分析，以测量状态切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，大脑的灵活性与 (熵和状态转换频率)和青少年的抑郁、NSSI和STB，表明潜在的 陷入消极思维和感觉中的神经机制。我们建议个人 儿童和青少年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出现抑郁和自杀风险的原因。在我们的概念中 模式、遗传和环境因素塑造了网络发展轨迹，而网络发展轨迹又是网络发展轨迹的基础 抑郁、NSSI和STB的出现。这项提议试图描绘出神经发育 额缘威胁、皮质-纹状体接近/奖励和默认模式下的力量和灵活性轨迹 与儿童抑郁症的风险、发病和早期病程、NSSI和STB相关的网络 ABCD研究中的青少年使用新的分析策略。这项研究的新见解将为 设计个性化干预措施以促进抑郁症和自杀风险的早期发现的基础， 并指导能够恢复大脑健康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.