Dopamine Availability and Developmental Pathways of Adolescent Depression and Anhedonia

多巴胺的可用性以及青少年抑郁症和快感缺失的发展途径

• 批准号: 10674750
• 负责人: Erika E Forbes
• 金额: $ 75.9万
• 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/10674750
• 关键词: Acceleration; 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; Involutional Depression; 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; System; TNF gene; Telephone; Testing; Text; Text Messaging; Time; Tissues; Ventral Striatum; Vesicle; child depression; depressive symptoms; disability; dopamine system; experience; hedonic; improved; inflammatory marker; interest; longitudinal design; motivated behavior; neural circuit; neurobehavioral; neuroinflammation; neuromelanin; neuroregulation; phenomenological models; presynaptic; 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.

项目总结/摘要 抑郁症是一种常见的，严重的精神病理学形式，与痛苦，残疾和 自杀抑郁症的特征是奖励功能被破坏，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期。的 多巴胺神经调节系统一直与抑郁症有关， 这反映在快感缺乏，这是抑郁症的一个主要症状， 享受愉快的体验。此外，多巴胺的功能被假定为介导的影响， 神经炎症对抑郁症的影响从发展的角度来看，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 回路，纹状体多巴胺的可用性，奖励驱动的行为，以及奖励集中的经验， 现实生活中的场景 这项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，多巴胺的变化，以及它们在典型发展背景下的关联， 捕获跨方法和域的关键构造。其翻译战略强调以下措施： 多巴胺的功能受到基础神经科学的启发。 这项研究将使用一种加速的方法， 纵向设计，在0、12和24个月时评估150名青少年（16-22岁），75名 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 范式和静止状态;奖赏预期和奖赏寻求的生态瞬时评价 行为;基于智能手机的运动活动和电话/文本活动的被动感测; 奖励动机;抑郁、快感缺乏和奖励功能的自我报告;循环测量 炎性标志物（例如，CRP、IL-6）。多巴胺功能将通过以下方法安全无创地测量： 核磁共振主要焦点将是通过R2 '的多巴胺可用性，R2'是组织铁的量度，其集中在 基底神经节与突触前多巴胺囊泡共定位，并且是多巴胺合成所必需的。 本研究将阐明抑郁症与多巴胺的关系及其可能的共同波动 以及炎症标记物通过多巴胺与抑郁症的潜在关联 空房的研究结果将与抑郁症的病理生理学、病程和治疗相关。