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

摘要 对抑郁症的神经成像研究表明，大脑反应性降低与获得显著相关 减少享乐基调(即快感缺乏症)和未来的严重抑郁症(MDD)。这项工作也有 提示大脑对丧失的反应性增加可能是抑郁症患者负性情绪增加的关键生物标志物 MDD和抑郁的风险也是如此。尽管令人信服的发现表明，享乐主义的语气减弱和 在学龄前儿童中，负面情绪的增加是MDD的重要危险因素，但很少有 研究神经反应性改变的发育时序，以获得和失去和增加 这个年龄段患抑郁症的早期情绪风险。拟议的研究的目的是开始填补这方面的知识 差距。为了实现这一目标，免费的功能性磁共振成像(FMRI)和活动相关 将在两个时间点收集200名4-7岁儿童对得失反应的潜在(ERP)测量 相隔1年。奖赏学习措施，被认为是将减少享乐基调与 随后，还将收集和检查MDD与大脑奖励反应的潜在关系。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。这个 拟议项目的可行性因研究小组良好的招聘和 追踪学龄前儿童的大样本，并在这么小的儿童中获得高质量的fMRI和ERP数据 使用对发展敏感的方法来适应和培训他们以适应这些环境的需求。 将在个人水平上进行系统的方法来研究大脑对得失的反应。 以前的研究表明，大脑区域是奖赏处理的关键区域，在抑郁症中也会受到干扰。它是 假设大脑在基线时获得收益的反应性减弱将与享乐性减弱相关 在基线和一年后测量音调和奖励学习。类似地，假设增加了 大脑对基线丧失的反应将与基线和1的负性情绪增加有关 一年后。还假设：1)在基线和随访之间增加大脑的反应性 评估将预测1年后享乐基调和奖励学习的增加，2)减少 在此期间，大脑对丧失的反应性将预示着一年后负面情绪的减少。重要的是， 目前的研究将调查fMRI和erp对大脑反应性得失的测量是否具有相似的作用。 在假想的关系中。通过研究学龄前儿童大脑对得失的反应 与情绪处理的早期变化有关，这种变化会增加这个年龄段患抑郁症的风险，目前 研究可能揭示独特的和早期出现的神经生物学标志物和神经发育轨迹 持续的情绪困难和/或后来的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 同样，在研究预测中，对未来临床使用这些方法至关重要的信息支持更早 还将获得识别和开发新的治疗方法，将抑郁症的公共卫生负担降至最低。

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.