Dopamine Availability and Developmental Pathways of Adolescent Depression and Anhedonia

多巴胺的可用性以及青少年抑郁和快感缺乏的发展途径

• 批准号: 10441702
• 负责人: Erika E Forbes
• 金额: $ 77.75万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10441702
• 关键词: Address; Adolescence; Adolescent; Age; Anhedonia; Basal Ganglia; Behavior; Behavioral; Brain; Cellular Phone; Clinical; Corpus striatum structure; Development; Disease; Dopamine; Ecological momentary assessment; Exhibits; Functional Magnetic Resonance Imaging; Functional disorder; Future; Impairment; Inflammation; Interleukin-6; Iron; Life; Life Experience; Link; Magnetic Resonance Imaging; Measurement; Measures; Medial; Mediating; Mental Depression; Methods; Midbrain structure; Motivation; Motor; Motor Activity; Neurosciences; Nucleus Accumbens; Pathway interactions; Pattern; Peripheral; Prefrontal Cortex; Psychopathology; Rest; Rewards; Role; Severities; Structure; Substantia nigra structure; Suicide; Support System; Synapses; System; TNF gene; Telephone; Testing; Text; Text Messaging; Time; Tissues; Ventral Striatum; Vesicle; base; child depression; depressive symptoms; disability; dopamine system; experience; hedonic; improved; inflammatory marker; interest; longitudinal design; motivated behavior; neural circuit; neurobehavioral; neuroinflammation; neuromelanin; neuroregulation; prevent; rate of change; response; reward anticipation; reward circuitry; self-reported depression; sensor; translational approach; young adult

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.

项目概要/摘要 抑郁症是一种常见、严重的精神病理学形式，与痛苦、残疾和 自杀。抑郁症的特点是奖赏功能被破坏，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时期。这 多巴胺神经调节系统始终与抑郁症相关，并被认为是特定的 反映在快感缺乏上，这是抑郁症的一个主要症状，涉及难以获得或获得动机 享受愉快的经历。此外，多巴胺功能被认为可以介导以下因素的影响： 抑郁症的神经炎症。从发展的角度，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领域的变化，包括额纹状体奖励 电路、纹状体中多巴胺的可用性、奖励驱动的行为以及以奖励为中心的体验 现实生活中的设置。 拟议的研究采用发展精神病理学和临床神经科学方法。它位于 抑郁症、多巴胺的变化及其与典型发展背景下的关联 捕获跨方法和领域的关键结构。其转化战略强调以下措施： 多巴胺功能受到基础神经科学的启发。 该研究将使用加速研究来检查多巴胺在青少年抑郁症中的发展途径 纵向设计，在 0、12 和 24 个月时对 150 名青少年（16-22 岁）进行评估，其中 75 名青少年 抑郁症和 75 名精神健康的人。青少年将完成磁共振成像 （MRI）评估多巴胺功能的会议；奖励期间额纹状体反应的功能性 MRI 范例和休息；奖励预期和奖励寻求的生态瞬时评估（EMA） 行为;基于智能手机的运动活动和电话/文本活动的被动传感；的行为任务 奖励动机；抑郁、快感缺乏和奖赏功能的自我报告；和循环测量 炎症标志物（例如 CRP、IL-6）。多巴胺功能将通过以下方式安全、无创地测量 核磁共振成像。主要关注点是通过 R2' 获得多巴胺，R2' 是组织铁的一种测量方法，主要集中在 基底神经节与突触前多巴胺囊泡共定位，是多巴胺合成所必需的。 该研究将阐明抑郁症和多巴胺可用性的关系以及它们可能的共同波动 整个青春期，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。