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

早期出现抑郁风险时奖励处理的神经发育轨迹

• 批准号: 9720313
• 负责人: Michael S Gaffrey
• 金额: $ 65.8万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2021-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9720313
• 关键词: 7 year old; Address; Age; Amygdaloid structure; Anhedonia; Behavioral; Biological Markers; Brain; Brain region; Child; Clinical; Data; Development; Developmental Course; Disease; Early identification; Emotional; Emotions; Environment; Event-Related Potentials; Feedback; Functional Magnetic Resonance Imaging; Future; Goals; Human; Image Analysis; Impairment; Individual; Individual Differences; Investigation; Knowledge; Lead; Learning; Life; Link; Major Depressive Disorder; Measures; Medial; Mental Depression; Mentored Patient-Oriented Research Career Development Award; Methods; Moods; Morbidity - disease rate; National Institute of Mental Health; Negative Valence; Neurobiology; Nursery Schools; Outcome; Positive Valence; Prefrontal Cortex; Prevalence; Preventive treatment; Procedures; Public Health; Recording of previous events; Research; Research Domain Criteria; Research Personnel; Research Priority; Rewards; Risk; Risk Factors; Sampling; Source; Strategic Planning; System; Techniques; Testing; Time; Training; Work; age group; behavior measurement; clinical application; connectome; depressive symptoms; disability; disorder risk; early onset; endophenotype; follow up assessment; hedonic; imaging modality; learned behavior; neuroimaging; novel; positive emotional state; programs; recruit; relating to nervous system; response; reward processing; therapy development

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.

抽象的 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抑郁症有显着相关性。 享乐基调减弱（即快感缺乏）和未来的重度抑郁症（MDD）。这部作品还 表明大脑对失去的反应增加可能是消极情绪增加的关键生物标志物 MDD 和抑郁症的风险也是如此。尽管令人信服的发现表明享乐基调和 消极情绪增加是学龄前儿童患 MDD 的重要危险因素，但很少有 研究检查改变神经反应性的获得和损失以及增加的发育时间 这个年龄段的早期情绪抑郁风险。拟议研究的目的是开始填补这些知识 差距。为了实现这一目标，免费的功能磁共振成像（fMRI）和事件相关 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 相差1年。奖励学习的措施被认为是连接减少享乐基调与 随后，MDD 也将被收集并检查与大脑奖励反应的潜在关系。一个 由研究人员和顾问组成的跨学科专家团队将支持拟议的研究计划。这 研究团队良好的招募和培训历史增强了拟议项目的可行性 跟踪大量学龄前儿童样本并获得如此年幼儿童的高质量功能磁共振成像和 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需求。 将在个体层面上进行系统性方法研究大脑对获得和损失的反应 此前研究表明，大脑区域对于奖励处理至关重要，但在抑郁症中会受到干扰。这是 假设大脑对基线增益的反应性减弱与享乐感减弱有关 在基线和一年后测量语气和奖励学习。同样，假设增加 大脑对基线损失的反应与基线时负面情绪的增加有关，1 一年后。还假设 1）增加大脑反应性以获得基线和后续结果之间的增益 评估将预测一年后享乐基调和奖励学习的增加，并且 2) 减少 大脑在这段时间内对损失的反应将预测一年后负面情绪的减少。重要的是， 当前的研究将调查大脑对获得和损失的反应的 fMRI 和 ERP 测量是否具有相似的作用 在假设的关系中。通过研究学龄前儿童的大脑对获得和损失的反应如何 与情绪处理的早期改变有关，增加了这个年龄段患抑郁症的风险，目前 研究可能揭示独特且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/或后来的抑郁症的风险。通过进一步研究fMRI和ERP功能是否 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可以支持早期 识别和开发新的治疗方法，最大限度地减少抑郁症的公共健康负担也将获得好处。