NEURODEVELOPMENTAL TRAJECTORIES OF REWARD PROCESSING IN VERY EARLY EMERGING RISK FOR DEPRESSION

摘要 抑郁症的神经影像学研究表明，大脑对增益的反应性降低与 减少享乐基调（即，快感缺失）和未来的重度抑郁症（MDD）。这项工作还 研究表明，大脑对损失的反应性增加可能是大脑中消极情绪增加的一个关键生物标志物。 MDD和抑郁症的风险。尽管令人信服的研究结果表明，减少享乐基调和 增加的负面情绪是学龄前儿童MDD的重要危险因素，很少有 研究了改变神经反应性的发育时间，以获得和损失，并增加 在这个年龄出现抑郁症的早期情绪风险。拟议研究的目的是开始填补这方面的知识 间隙为了促进这一目标，免费的功能性磁共振成像（fMRI）和事件相关的 将在两个时间点收集200名4-7奥尔兹对获得和损失的反应的潜在（ERP）措施 1-年分开。奖励学习的措施，被认为是一个关键的机制，连接减少享乐基调， 随后，MDD也将被收集并检查与大脑对奖励的反应性的潜在关系。一个 由调查人员和顾问组成的跨学科专家小组将支持拟议的研究计划。的 研究团队良好的招聘历史增强了拟议项目的可行性， 通过对学龄前儿童的大样本跟踪，并在这么小的孩子中获得高质量的fMRI和ERP数据， 使用发育敏感的方法来适应和训练他们适应这些环境的要求。 一个系统的方法调查大脑反应的获得和损失将进行在个人的水平 大脑区域先前被证明对奖励处理至关重要，并在抑郁症中被破坏。是 假设基线时大脑对增益的反应性降低与享乐性降低相关， 在基线和1年后测量音调和奖励学习。同样，据推测， 基线时对损失的大脑反应性将与基线时增加的负面情绪相关， 一年后。还假设1）在基线和随访之间增加大脑对增益的反应性 评估将预测1年后的快乐情绪和奖励学习增加，2） 在这段时间内，大脑对损失的反应将预测1年后消极情绪的下降。重要的是 目前的研究将调查功能磁共振成像和ERP测量大脑对获得和失去的反应是否相似 在假设的关系中。通过研究学龄前儿童的大脑对获得和失去的反应， 与情绪处理的早期改变相关，增加了这个年龄段抑郁症的风险，目前， 研究可能揭示了独特的和早期发生的神经生物学标记和神经发育轨迹， 持续情绪困难和/或后期MDD的风险。通过进一步研究功能磁共振成像和事件相关电位功能 类似地，在研究预测中，对于这些方法的未来临床使用至关重要的信息， 还将获得识别和开发新治疗方法，以最大限度地减少抑郁症的公共卫生负担。

ABSTRACT Neuroimaging studies of depression have suggested that reduced brain reactivity to gain is significantly linked to diminished hedonic tone (i.e., anhedonia) and future Major Depressive Disorder (MDD). This work has also suggested that increased brain reactivity to loss may be a key biomarker of increased negative emotionality in MDD and risk for depression as well. Despite compelling findings suggesting that diminished hedonic tone and increased negative emotionality are significant risk factors for MDD in preschoolers, there have been very few investigations examining the developmental timing of altered neural reactivity to gain and loss and increased early emotional risk for depression at this age. The purpose of proposed study is to begin filling this knowledge gap. To facilitate this goal, complimentary functional magnetic resonance imaging (fMRI) and event related potential (ERP) measures of response to gain and loss will be collected in 200 4-7 year olds at two time points 1-year apart. Measures of reward learning, suggested to be a key mechanism linking reduced hedonic tone to later MDD, will also be collected and examined for potential relationships with brain reactivity to reward. An expert interdisciplinary team of investigators and consultants will support the proposed research plan. The feasibility of the proposed project is enhanced by the study team's well established history of recruiting and following large samples of preschoolers and in obtaining high quality fMRI and ERP data in children this young using developmentally sensitive methods to acclimate and train them for the demands of these environments. A systematic approach investigating brain reactivity to gain and loss will be conducted at the level of individual brain regions previously shown to be critical for reward processing and disrupted in depression. It is hypothesized that diminished brain reactivity to gain at baseline will be associated with diminished hedonic tone and reward learning measured at baseline and 1 year later. Similarly, it is hypothesized that increased brain reactivity to loss at baseline will be associated with increased negative emotionality at baseline and 1 year later. It is also hypothesized that 1) increasing brain reactivity to gain between baseline and follow-up assessments will predict increased hedonic tone and reward learning 1 year later and that 2) decreases in brain reactivity to loss during this time will predict decreased negative emotionality 1 year later. Importantly, the current study will investigate whether fMRI and ERP measures of brain reactivity to gain and loss act similarly in the hypothesized relationships. By studying how brain reactivity to gain and loss in preschoolers is associated with early alterations in emotion processing that increase risk for depression at this age, the current study may reveal unique and early occurring neurobiological markers and neurodevelopmental trajectories of risk for continued mood difficulties and/or later MDD. By further investigating whether fMRI and ERP function similarly in study predictions, information critical for the future clinical use of these methods to support earlier identification and develop novel treatments minimizing depression's public health burden will also be gained.