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

项目摘要/摘要 重度抑郁障碍(MDD)是所有疾病中最普遍、反复发作和功能衰弱的疾病之一。 精神障碍。MDD的发病率在青春期急剧上升，患有 在青春期起病的MDD往往比那些患有MDD的人有更慢性和更严重的抑郁病程 起病较晚。因此，迫切需要制定有效的办法，以便及早查明、预防、 以及对MDD的干预。早期生活逆境(ELA)的经历影响着超过40%的儿童，是一种 MDD的强预测因子。研究表明，ELA增加MDD风险的一个途径是通过 与应激反应有关的额叶边缘区域结构和功能发育的改变 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展开尚不清楚。此外， ELA影响神经发育和MDD风险的生物行为机制还不是很好 明白了。在这种情况下，睡眠障碍是终生MDD的一个重要风险因素，是一种 在青春期，ELA可能增加MDD风险的途径未被充分探索。睡眠障碍 在青春期，由于规范的生物和心理社会变化的综合作用，这一比例往往会增加； 事实上，超过70%的高中生报告睡眠不足。新出现的研究表明 睡眠障碍较大的青少年，其脑白质发育受阻的部位 连接额缘区域，增强额缘对压力的反应性。重叠的神经生物学 ELA和睡眠障碍对健康的影响表明，睡眠障碍是连接 ELA到额叶边缘改变和MDD风险增加。拟议的研究解决了以下方面的关键差距 通过研究ELA、睡眠障碍和额叶边缘的多变量和纵向影响的文献 青春期的连接性以及这些因素如何预测青春期患抑郁症的风险。 利用来自多方法纵向研究的数据，建议的项目调查睡眠障碍 作为连接ELA与额叶边缘发育改变和青春期MDD风险的途径 青壮年(9-20岁)。这个项目的成果不仅将增加我们对 ELA与MDD风险增加有关的神经生物学机制，但也将提供洞察力 将睡眠障碍作为青春期干预的潜在目标，以改善 埃拉。此外，拟议的培训计划将使申请者能够获得理论和方法 擅长研究ELA、睡眠质量、额叶边缘发育和精神病理学之间的关系 在青春期，并培养过渡到独立研究所需的专业技能 职业生涯。申请者将接受培训的斯坦福大学拥有专家和资源 与提案的所有领域相关，使其成为申请者理想的培训环境。

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.