The Contribution of Stressful Life Events and Insufficient Sleep to Reward-Related Brain Function and Depression in Adolescent Girls

描述(由申请者提供)：这项指导研究科学家发展奖(K01)将为候选人提供发展情感神经科学和精神病理学方面的高级培训。这项拟议的研究将测试一种新的抑郁症神经发育模型，在该模型中，紧张的生活事件和睡眠不足通过扰乱与奖励相关的神经回路的发展来增加青少年患抑郁症的风险。有两项研究被用来检验这一抑郁模型。第一项研究将评估神经和行为对奖励和抑郁症状的反应是否与前一周的日常压力生活事件和睡眠时间有关。这项研究的参与者将从一项正在进行的关于青春期女孩的神经回报回路和抑郁风险的纵向fMRI研究中招募。第二项研究将评估增加睡眠时间是否可以增加对奖励的神经和行为反应，并减少18至20岁睡眠不足和抑郁症状的女孩的抑郁症状。这项研究的参与者将从大学和学院的卫生诊所和周围社区招募。结合起来，这些研究将有助于将奖励处理作为抑郁症发病的一种假定机制，并提供关于延长睡眠时间作为干预青春期晚期女孩抑郁症状的有效性的数据。这位候选人在与拟议项目相关的几个领域拥有专业知识，包括抑郁症的情感偏见，睡眠在认知过程和精神病理学中的作用，以及认知神经科学的研究方法。她将通过她的K01发展以下方面的专业知识：1)奖励回路神经发育；2)应激生活事件和生理应激反应；3)睡眠和昼夜节律；以及4)纵向数据分析的高级技能。匹兹堡大学是实现这些研究和培训目标的理想环境，原因有两个。首先，申请人挑选的导师埃里卡·福布斯博士和马蒂卡·霍尔博士都是非常成功的独立调查人员，他们都有丰富的指导经验，并在压力和睡眠作为与奖励相关的神经回路和抑郁症状异常发展的风险因素方面拥有共同的专业知识。其次，匹兹堡大学是情感发育神经科学和睡眠研究的主要中心之一。拟议的研究和培训计划将有助于未来的R01应用，该应用将检查神经和行为对奖励的反应，以及神经和生理对压力的纵向反应，作为青少年精神病理学的机制。这一申请符合国家精神卫生研究所为研究神经回路的发展和功能、异常发展轨迹的机制和修饰物的优先事项，重点是对干扰敏感的时期，以及与精神病理学相关的功能基本维度(例如，正价系统)研究的研究领域标准标准。

DESCRIPTION (provided by applicant): This Mentored Research Scientist Development Award (K01) will provide the candidate with advanced training in developmental affective neuroscience and psychopathology. The proposed research will test a novel neurodevelopmental model of depression in which stressful life events and insufficient sleep increase risk for depression in adolescents by disrupting the development of reward-related neural circuitry. Two studies are proposed to test this model of depression. The first study will evaluate whether neural and behavioral response to rewards and depressive symptoms are associated with daily stressful life events and sleep duration from the previous week. Participants for this study will be recruited from an ongoing longitudinal fMRI study of neural reward circuitry and risk for depression in adolescent girls. The second study will evaluate whether increasing sleep duration can increase neural and behavioral response to rewards and decrease depressive symptoms in 18- to 20-year-old girls with insufficient sleep and depressive symptoms. Participants for this study will be recruited from university and college health clinics and the surrounding community. In combination, these studies will help characterize reward processing as a putative mechanism of depression onset and provide data on the efficacy of sleep extension as an intervention for depressive symptoms in late adolescent girls. The candidate has expertise in several domains relevant to the proposed project, including affective bias in depression, the role of sleep in cognitive processing and psychopathology, and cognitive neuroscience research methods. She will build on this experience through her K01 by developing expertise in: 1) reward circuit neurodevelopment in late adolescence; 2) stressful life events and physiological stress-reactivity; 3) sleep and circadian rhythms; and 4) advanced skills for longitudinal data analysis. The University of Pittsburgh is an ideal environment to accomplish these research and training aims for two reasons. First, the applicant's selected mentors, Drs. Erika Forbes and Martica Hall, are both highly successful independent investigators with extensive mentorship experience and collective expertise in stress and sleep as risk factors for aberrant development of reward-related neural circuitry and depressive symptoms. Second, the University of Pittsburgh is one of the premier centers for affective developmental neuroscience and sleep research. The proposed research and training plan will contribute to a future R01 application that will examine neural and behavioral response to rewards and neural and physiological response to stress longitudinally as mechanisms of psychopathology in adolescents. This application is consistent with priorities outlined by the National Institute of Mental Health for research on the development and function of neural circuits, mechanisms and modifiers of aberrant developmental trajectories with a focus on periods of sensitivity to disruption, and Research Domain Criteria standards for research on basic dimensions of functioning (e.g., positive valence systems) that are relevant to psychopathology.