The Effects of Early Life Stress on the Development of Brain Networks: Predicting Risk for Depression and Suicidal Ideation in Adolescence

项目总结/摘要 早期生活压力（ELS），包括虐待，忽视和损失，与终身风险的急剧增加有关 心理健康问题的发展，如抑郁症和自杀念头。此外，本发明还提供了一种方法， 抑郁的青少年表现出异常的大脑网络，涉及情感，认知， 奖励和自我参照处理。许多这些网络的改变也与ELS有关 自杀意念（SI）因此，ELS可能影响抑郁相关脑的发育 网络，并有助于抑郁发作和SI的风险。神经发育机制 然而，ELS可能通过哪些途径带来这些负面结果的风险还没有得到很好的理解。在 在这项研究中，我们将首次研究青少年大脑网络的发育， ELS水平，以表征与重度抑郁症出现相关的轨迹 疾病（MDD）和SI。为此，我们将评估ELS对大脑网络发展的影响 纵向通过青春期阐明风险相关的神经生物学机制。此外，我们将 检查网络发展，抑郁症状和SI的并行和纵向关联， 不同程度的ELS。最后，我们将确定网络的发展轨迹是否 预测MDD和SI的发作。这项研究的结果不仅将增加我们对 ELS，脑网络发育和MDD和SI的心理健康结果之间的关系，但也将 提供洞察抑郁症和SI在青春期的关键时期，一个阶段， 增加了精神健康问题发生的风险。此外，这项研究将推动我们的 了解暴露于ELS但未暴露于ELS的青少年的神经保护机制 出现抑郁和/或自杀症状。家庭和个人水平的调解人之间的早期生活压力 MDD和SI的出现也将与大脑网络的发展有关。因此我们 预计目前的研究将有助于我们理解两种发病模型， ELS后的精神病理学和ELS赋予高风险的神经生物学机制， 负面的心理健康结果。拟议研究的结果将增加我们对 抑郁症和SI的发展神经生物学，并将提供洞察的发病和进展， 早期逆境后的混乱

Project Summary/Abstract Early life stress (ELS), including abuse, neglect, and loss, is associated with dramatic increases in lifelong risk for the development of mental health difficulties, such as depression and suicidal thoughts. In addition, depressed adolescents exhibit anomalies in networks of the brain that are involved in affective, cognitive, reward, and self-referential processing. Alterations in many of these networks are also associated with ELS and suicidal ideation (SI). Thus, it is possible that ELS affects the development of depression-related brain networks and contributes to risk for depressive episodes and SI. The neurodevelopmental mechanisms through which ELS might confer risk for these negative outcomes, however, are not well understood. In the proposed study, we will examine, for the first time, brain network development in adolescents with varying levels of ELS, in order to characterize trajectories that are associated with emergence of major depressive disorder (MDD) and SI. To this end, we will assess the effects of ELS on the development of brain networks longitudinally through adolescence to elucidate risk-related neurobiological mechanisms. In addition, we will examine concurrent and longitudinal associations of network development, depressive symptoms, and SI in youth with varying levels of ELS. Finally, we will determine whether developmental trajectories of networks predict the onset of MDD and SI. The results of this study will not only increase our understanding of the relations among ELS, brain network development, and mental health outcomes of MDD and SI, but will also provide insight into neuromarkers of depression and SI during the critical period of adolescence, a stage of increased risk for the onset of mental health difficulties. In addition, this research will advance our understanding of neuroprotective mechanisms in adolescents who have been exposed to ELS and yet do not develop depression and/or suicidal symptoms. Familial- and individual-level mediators between early life stress and the emergence of MDD and SI will also be examined in relation to brain network development. Thus, we anticipate that the current study will contribute to our understanding both of models of the onset of psychopathology following ELS and of neurobiological mechanisms by which ELS confers heightened risk for negative mental health outcomes. Findings from the proposed study will increase our knowledge of the developmental neurobiology of depression and SI, and will provide insight into the onset and progression of disorder following early adversity.