Effects of Early Life Stress and Sleep Disturbance on Frontolimbic Development and Risk for Depression Across Adolescence

早期生活压力和睡眠障碍对前肢发育和青春期抑郁风险的影响

• 批准号: 10820857
• 负责人: Jessica Phuong Uy
• 金额: $ 7.43万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-13 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10820857
• 关键词: 10 year old; 20 year old; Address; Adolescence; Adolescent; Affect; Affective; Age; Amygdaloid structure; Anterior; Area; Attenuated; Biological; Brain; Brain region; Child; Childhood; Chronic; Cognitive; Critical Pathways; Data; Data Collection; Development; Diagnosis; Dorsal; Early identification; Ecological Change; Environment; Exhibits; Experimental Designs; Exposure to; Family; Growth; Health; High School Student; Hippocampus; Hour; Incidence; Individual; Institution; Intervention; Lateral; Link; Literature; Longevity; Longitudinal Studies; Major Depressive Disorder; Mediating; Mediation; Mental Depression; Mental disorders; Methodology; Methods; Modeling; Nature; Neurobiology; Onset of illness; Participant; Pathway interactions; Population; Predictive Factor; Prefrontal Cortex; Prevalence; Prevention; Process; Psychopathology; Puberty; Recommendation; Recurrence; Regulation; Reporting; Research; Resources; Risk; Risk Factors; Severities; Sleep; Sleep Deprivation; Sleep Disorders; Sleep disturbances; Stress; Structure; Techniques; Time; Training; United States; Universities; Youth; affective neuroscience; attenuation; biobehavior; career; data acquisition; depressive symptoms; disability; early experience; early life adversity; early life stress; experience; insight; interest; multimodal data; negative affect; neglect; neurobiological mechanism; neurodevelopment; novel; psychosocial; risk prediction; skills; sleep quality; stress reactivity; white matter; young adult

Project Summary/Abstract Major depressive disorder (MDD) is among the most prevalent, recurrent, and functionally debilitating of all psychiatric disorders. The incidence of MDD rises sharply during adolescence, and individuals who have an onset of MDD in adolescence tend to have a more chronic and severe course of depression than do those with a later onset. Thus, there is an urgent need to develop effective approaches for early identification, prevention, and intervention for MDD. Experiences of early life adversity (ELA), which affect over 40% of children, are a strong predictor of MDD. Research suggests that one pathway by which ELA increases risk for MDD is through alterations in the structural and functional development of frontolimbic regions implicated in stress reactivity and regulation; however, the direction of these effects and how they unfold over time are not known. Moreover, the biobehavioral mechanisms by which ELA influences neurodevelopment and risk for MDD are not well understood. In this context, sleep disturbances is a significant risk factor for MDD across the lifespan and is an underexplored pathway by which ELA might increase risk for MDD during adolescence. Sleep disturbances tend to increase during adolescence due to a combination of normative biological and psychosocial changes; indeed, over 70% of high-school students report getting insufficient sleep. Emerging research suggests that adolescents with greater sleep disturbances have both attenuated white matter development in tracts that connect frontolimbic regions and heightened frontolimbic reactivity to stress. The overlapping neurobiological and health effects of ELA and sleep disturbances suggest that sleep disturbance is a critical pathway that links ELA to frontolimbic alterations and increased risk for MDD. The proposed research addresses critical gaps in the literature by examining the multivariate and longitudinal effects of ELA, sleep disturbances, and frontolimbic connectivity during adolescence and how these factors predict risk for depression in young adulthood. Leveraging data from a multimethod longitudinal study, the proposed project investigates sleep disturbances as a pathway linking ELA with alterations in frontolimbic development and risk for MDD across adolescence and young adulthood (9-20 years of age). The results of this project will not only increase our understanding of the neurobiological mechanisms by which ELA relates to increased risk for MDD, but will also provide insight into sleep disturbances as a potential target of intervention during adolescence to ameliorate the effects of ELA. Moreover, the proposed training plan will enable the applicant to gain theoretical and methodological expertise in studying the relations among ELA, sleep quality, frontolimbic development, and psychopathology during adolescence, and to develop professional skills necessary to transition to an independent research career. Stanford University, the institution at which the applicant will be training, has experts and resources relevant to all domains of the proposal, making it an ideal training environment for the applicant.

项目概要/摘要 重度抑郁症 (MDD) 是所有疾病中最常见、最易复发且功能衰弱的疾病之一 精神疾病。 MDD 的发病率在青春期急剧上升，患有 MDD 的人 与患有MDD的人相比，在青春期发病的MDD往往有更慢性和更严重的抑郁病程。 发病较晚。因此，迫切需要制定有效的方法来早期识别、预防、 以及 MDD 的干预。超过 40% 的儿童受到早期生活逆境 (ELA) 的影响， MDD 的强预测因子。研究表明，ELA 增加 MDD 风险的途径之一是通过 与应激反应有关的额边缘区域结构和功能发育的变化 和监管；然而，这些影响的方向以及它们如何随着时间的推移而显现尚不清楚。而且， ELA 影响神经发育和 MDD 风险的生物行为机制尚不清楚 明白了。在这种情况下，睡眠障碍是整个生命周期中 MDD 的一个重要危险因素，也是一个重要的风险因素。 ELA 可能增加青春期 MDD 风险的途径尚未被探索。睡眠障碍 由于规范的生物和心理社会变化的结合，在青春期往往会增加； 事实上，超过 70% 的高中生表示睡眠不足。新兴研究表明 睡眠障碍较严重的青少年，其大脑皮层的白质发育均减弱 连接额边缘区域并增强额边缘对压力的反应性。重叠的神经生物学 ELA 和睡眠障碍对健康的影响表明，睡眠障碍是将 ELA 对额叶的改变和 MDD 的风险增加。拟议的研究解决了以下方面的关键差距 通过检查 ELA、睡眠障碍和额边缘的多变量和纵向效应来查阅文献 青春期的连通性以及这些因素如何预测成年早期抑郁的风险。 拟议项目利用多方法纵向研究的数据来调查睡眠障碍 作为将 ELA 与额边缘发育变化和整个青春期 MDD 风险联系起来的途径 和青年期（9-20 岁）。这个项目的结果不仅会增加我们对 ELA 与 MDD 风险增加相关的神经生物学机制，但也将提供见解 将睡眠障碍作为青春期干预的潜在目标，以改善睡眠障碍的影响 埃拉。此外，拟议的培训计划将使申请人能够获得理论和方法论 研究 ELA、睡眠质量、额边缘发育和精神病理学之间关系的专业知识 在青春期，并培养过渡到独立研究所需的专业技能 职业。申请人将在斯坦福大学接受培训，拥有专家和资源 与提案的所有领域相关，使其成为申请人的理想培训环境。