Dopamine Availability and Developmental Pathways of Adolescent Depression and Anhedonia

项目摘要/摘要 抑郁症是一种常见的、严重的精神病理形式，与痛苦、残疾和 自杀。抑郁症的特征是奖赏功能紊乱，通常始于青春期， 支持奖励驱动行为的神经行为系统变化的关键发育期。这个 多巴胺神经调节系统一直与抑郁症有关，并被认为是特异性的 表现为快感缺乏，这是抑郁症的一种主要症状，涉及缺乏动力或缺乏动力 享受愉快的体验。此外，多巴胺功能被假定为介导了 抑郁症的神经炎症。在发育方面，了解多巴胺在抑郁症中的作用 需要检查奖励功能随时间和跨域的变化，包括额纹状体奖励 纹状体中的回路、多巴胺的可获得性、奖赏驱动的行为和关注奖赏的体验 现实生活中的场景。 这项拟议的研究采用了发展精神病理学和临床神经科学的方法。它位于 抑郁症、多巴胺及其相关性的变化与典型发育和 跨方法和域捕获关键构造。它的翻译战略强调采取措施 多巴胺的功能受到基础神经科学的启发。 这项研究将研究青少年抑郁症中多巴胺的发育途径，使用加速的 纵向设计，分别在0、12和24个月对150名青少年(16-22岁)、75名 抑郁症患者和75名精神健康患者。青少年将完成核磁共振成像 用于评估多巴胺功能的(MRI)会议；奖励期间额纹状体反应的功能MRI 范式与静态；奖赏预期与奖赏寻求的生态瞬时评估 行为；基于智能手机的运动活动和电话/文本活动的被动感知；行为任务 奖励动机；抑郁、快感缺乏和奖励功能的自我报告；循环的测量 炎症标志物(如CRP、IL-6)。多巴胺功能将通过安全和非侵入性的 核磁共振检查。主要的焦点将是通过R2‘获得多巴胺，R2’是组织铁的一种衡量标准，它集中在 基底节与突触前的多巴胺小泡共定位，是多巴胺合成所必需的。 这项研究将阐明抑郁症和多巴胺可获得性的关系，以及它们可能的共同波动 在青春期，以及炎症标志物通过多巴胺与抑郁症的潜在关联 可用性。研究结果将与抑郁症的病理生理学、病程和治疗相关。

Project Summary/Abstract Depression is a common, serious form of psychopathology that is associated with suffering, disability, and suicide. Depression is characterized by disrupted reward function and typically begins during adolescence, a key developmental period for change in neurobehavioral systems supporting reward-driven behavior. The dopamine neuromodulatory system is consistently associated with depression and thought to be specifically reflected in anhedonia, a cardinal symptom of depression that involves difficulty with motivation for or enjoyment of pleasant experiences. Furthermore, dopamine function is postulated to mediate the influence of neuroinflammation on depression. Developmentally, understanding the role of dopamine in depression requires examining changes in reward function over time and across domains, including frontostriatal reward circuitry, dopamine availability in the striatum, reward-driven behavior, and reward-focused experiences in real-life settings. The proposed study uses a developmental psychopathology and clinical neuroscience approach. It situates changes in depression, dopamine, and their association against a backdrop of typical development and captures key constructs across methods and domains. Its translational strategy emphasizes measures of dopamine function inspired by basic neuroscience. The study will examine developmental pathways of dopamine in adolescent depression, using an accelerated longitudinal design with assessments at 0, 12, and 24 months in 150 adolescents (age 16-22), 75 with depression and 75 who are psychiatrically healthy. Adolescents will complete a magnetic resonance imaging (MRI) session to assess dopamine function; functional MRI of frontostriatal response during a reward paradigm and at rest; ecological momentary assessment (EMA) of reward anticipation and reward-seeking behavior; smartphone-based passive sensing of motor activity and phone/text activity; behavioral tasks of reward motivation; self-report of depression, anhedonia, and reward function; and measurement of circulating inflammatory markers (e.g., CRP, IL-6). Dopamine function will be measured safely and noninvasively through MRI. The primary focus will be dopamine availability via R2’, a measure of tissue iron, which is concentrated in the basal ganglia, co-localizes with pre-synaptic dopamine vesicles, and is necessary for dopamine synthesis. The study will elucidate the relation of depression and dopamine availability, their possible co-fluctuation across adolescence, and the potential association of inflammatory markers with depression through dopamine availability. Findings will have relevance to the pathophysiology, course, and treatment of depression.