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

基本信息

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
项目类别：
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

项目摘要

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、残疾和抑郁症的特点是奖赏功能受损，通常始于青春期，这是一种自杀行为。支持奖励驱动行为的神经行为系统变化的关键发育时期。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此外，多巴胺功能被认为可以调节愉快经历的影响。神经炎症对抑郁症的影响，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。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。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 名精神健康的青少年将完成磁共振成像。 (MRI) 评估奖励期间额纹状体反应的多巴胺功能的会议；奖励预期和奖励寻求的范式和静止状态的生态瞬时评估（EMA）行为；基于智能手机的运动活动和电话/文本活动的被动感知；奖励动机；抑郁、快感缺乏和奖励功能的自我报告和循环测量；炎症标记物（例如 CRP、IL-6）将通过安全且无创的方式进行测量。主要关注点是通过 R2' 获得多巴胺，这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研究结果将与抑郁症的病理生理学、病程和治疗相关。