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

大脑网络强度和灵活性的发展轨迹：与青少年抑郁和自残风险、发作和过程的关系

• 批准号: 10601072
• 负责人: Kathryn Regan Cullen
• 金额: $ 38.3万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10601072
• 关键词: Adolescence; Adolescent; Adolescent and Young Adult; Adult; Age; Biology; Brain; Cause of Death; Child; Childhood; Clinical; Cognitive; Corpus striatum structure; Data; Data Collection; Data Set; Development; Early Diagnosis; Early Intervention; Entropy; Environment; Environmental Risk Factor; Family; Feeling; Feeling suicidal; Foundations; Frequencies; Functional Magnetic Resonance Imaging; Future; Impulsivity; Individual Differences; Information Theory; Intervention; Knowledge; Laboratories; Link; Measures; Mediating; Mental Depression; Methods; Modeling; Neurosciences; Outcome; Persons; Population Study; Puberty; Recording of previous events; Reporting; Reproducibility; Research; Rest; Rewards; Risk; Risk Factors; Sampling; Self-Injurious Behavior; Shapes; Signal Transduction; Structure; Suicide; Suicide attempt; Suicide prevention; Symptoms; System; Thinking; Validation; Youth; adolescent-onset depression; brain shape; child depression; cognitive development; design; flexibility; follow-up; functional MRI scan; genetic risk factor; improved; insight; longitudinal design; neural; neural network; neuroimaging; neuromechanism; non-suicidal self injury; novel; novel strategies; personalized intervention; prevent; sex; stressor; suicidal behavior; suicidal morbidity; suicidal risk

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.

抽象的 抑郁症，非杀伤性自伤（NSSI）和自杀思想和行为（STB）通常出现 青年和每个人都代表着自杀的重要危险因素。早期检测和干预具有 有望改变轨迹，改善成人结果并预防自杀。实施的大脑网络 抑郁症（额叶威胁，皮层纹状体方法/奖励和默认模式）经历了重大 儿童和青少年时期的变化；这些变化如何展开的方式可能对 了解抑郁症，NSSI和STB的发作和过程。青春期的大脑认知 开发（ABCD）是一项基于人群的研究，每年都有11,000多名儿童超过10名儿童 多年来，最初三年的临床和神经影像学数据已经公开可用。自ABCD以来 数据收集涵盖了一个关键的发育窗口，这是抑郁症，NSSI和 STB，分析此数据为表征神经网络之间的联系提供了理想的机会 年轻人的自杀风险的变化和发展风险。静止状态fMRI（RS-FMRI）可用于表征大脑 网络结构和组织。而我们的实验室和其他实验室已广泛应用标准 功能连接方法使用横截面表征抑郁网络内强度的强度 设计，需要纵向设计才能理解网络强度的异常发展可能 有助于发作抑郁，NSSI和STB。最近，出现了新颖的方法来估计 RSFMRI数据的网络灵活性。这些包括从信息理论绘制到测量的熵 大脑信号以及从动态连通性分析到测量状态转换或大脑之间的移位 休息期间的网络配置。我们的初步数据指向大脑灵活性之间的反比关系 （熵和状态转换频率）和抑郁症，青少年的NSSI和STB，表明潜力 以消极的思维和感觉方式“卡住”的神经机制。我们提出了这个人 神经元网络强度和柔韧性变化的轨迹的差异， 青少年可能有助于解释青少年抑郁症和自杀风险的出现。在我们的概念上 模型，继承和环境因素塑造网络发展轨迹，而这又是基础 抑郁症，NSSI和STB的出现。该建议旨在描述神经发育 额 - 纹状体威胁，皮质 - 纹状体方法/奖励和默认模式的力量和灵活性的轨迹 与抑郁症的风险，发作和早期过程相关的网络，儿童的NSSI和STB以及 ABCD研究的青少年使用新颖的分析策略。这项研究的新见解将提供 设计个性化干预措施以促进抑郁症和自杀风险的促进基金会， 并指导能够恢复健康大脑发育并避免严重负面的干预措施 包括自杀在内的结果。