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

项目摘要/摘要 早期生活压力(ELS)，包括虐待、忽视和丧失，与终身风险的急剧增加有关 对于精神健康发展有困难的人，如抑郁和自杀念头。此外, 抑郁的青少年表现出大脑网络的异常，这些网络涉及情感，认知， 奖赏和自我参照加工。其中许多网络的改变也与ELS有关 和自杀意念(SI)。因此，ELS可能影响抑郁症相关脑的发育。 网络，并增加抑郁发作和SI的风险。神经发育机制 然而，ELS可能通过哪些途径为这些负面结果带来风险，目前还没有很好的理解。在 拟议的研究，我们将第一次检查不同年龄的青少年的大脑网络发育。 ELS水平，以便描述与重度抑郁的出现相关的轨迹 精神障碍(MDD)和SI。为此，我们将评估ELS对大脑网络发展的影响 通过青春期纵向阐明与风险相关的神经生物学机制。此外，我们还将 检查网络发展、抑郁症状和SI之间的同步和纵向关联 有不同水平ELS的年轻人。最后，我们将确定网络的发展轨迹是否 预测MDD和SI的发病。这项研究的结果不仅将增加我们对 精神障碍和精神障碍的ELS、脑网络发育和心理健康结局之间的关系，但也将 提供对青春期关键时期抑郁和SI的神经标记物的洞察，这是 出现心理健康困难的风险增加。此外，这项研究将促进我们的 已接触ELS但尚未接触ELS的青少年对神经保护机制的了解 出现抑郁和/或自杀症状。家庭和个人水平在早期生活压力之间的中介作用 MDD和SI的出现也将与大脑网络发育相关。因此，我们 预计目前的研究将有助于我们对两种发病模式的理解 ELS后的精神病理学以及ELS导致高危的神经生物学机制 消极的心理健康后果。拟议研究的结果将增加我们对 抑郁症和SI的发育神经生物学，并将提供对抑郁症的发生和发展的洞察 早年的逆境之后的混乱。

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.