Circadian Rhythms and Sleep, Structural Neuroimaging and Depression in People with Multiple Sclerosis

多发性硬化症患者的昼夜节律和睡眠、结构神经影像学和抑郁症

• 批准号: 10231164
• 负责人: Kathryn C. Fitzgerald
• 金额: $ 17.93万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-10 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10231164
• 关键词: Adverse effects; Arousal and Regulatory Systems; Atrophic; Automobile Driving; Award; Biological; Biology; Brain; Brain Pathology; CNS autoimmune disease; Central Nervous System Diseases; Chronic; Circadian Rhythms; Clinical; Data; Data Analyses; Data Collection; Demyelinations; Depressed mood; Development; Disease; Early Diagnosis; Enrollment; Etiology; Evaluation; Future; Goals; Hour; Inflammatory; Inflammatory Response; Instruction; Interview; K-Series Research Career Programs; Lesion; Light; Link; Longitudinal Studies; Magnetic Resonance Imaging; Major Depressive Disorder; Mediating; Mental Depression; Mentors; Methods; Modeling; Moods; Morbidity - disease rate; Multiple Sclerosis; National Institute of Mental Health; Neurodegenerative Disorders; Nucleic Acid Regulatory Sequences; Observational Study; Participant; Pathway interactions; Pattern; Pilot Projects; Population; Population Research; Prevalence; Prevention; Prevention strategy; Regulation; Research; Research Domain Criteria; Research Personnel; Risk; Risk Factors; Scientist; Site; Sleep; Sleep Deprivation; Sleep disturbances; Standardization; Structure; System; Testing; Training; Training Programs; Wrist; actigraphy; circadian; comorbidity; contrast enhanced; cost; data infrastructure; depressive symptoms; disability; disorder risk; experience; gray matter; high risk; high risk population; imaging study; improved; insight; longitudinal analysis; longitudinal design; meetings; mortality; multiple sclerosis patient; neurobiological mechanism; neuroimaging; novel; poor sleep; programs; recruit; research study; skills; sleep quality; symptom management; systemic inflammatory response; tool; treatment strategy

PROJECT SUMMARY This application is for a Mentored Research Scientist Career Development Award (K01). The award will provide the candidate with enhanced skills and necessary training to build a research program that investigates the increased burden of depression in autoimmune diseases of the central nervous system (CNS) with a particular focus on multiple sclerosis (MS). People with MS are a markedly higher risk for psychiatric comorbidities, including depression. Estimates of lifetime prevalence of major depression in people with MS reach 50% and are nearly twice that of those with other chronic conditions. Depression is also linked with excess MS-associated morbidity and mortality. However, the specific mechanisms and risk factors driving the increased burden of depression in MS are not well-understood. The goal of the proposed project is to provide the candidate with advanced skills needed to establish an independent program focused on understanding neurobiological mechanisms of depression people with MS that will better inform treatment and prevention strategies in this high- risk population. The composite, comprehensive training plan proposed combines formal coursework, didactic instruction from her mentors, applied hands-on data collection and analysis sessions and attendance at scientific seminars and meetings. Primary training goals include 1) gaining a deeper understanding of depression biology to better inform studies of risk and prevention, 2) experience in the assessment of depression in large population- based research studies, 3) skills in applied structural neuroimaging analysis as tools to better understand neuroanatomical changes as they relate to depressive symptoms. Other training goals involve gaining critical experience in the evaluation of potential risk upstream risk factors for depression in MS. Specifically, the candidate will receive training in sleep and circadian rhythm biology and evaluation, which are two related and biologically plausible contributors to depression in MS. This comprehensive, composite training program will allow the candidate to leverage existing data and infrastructure from a large on-going observational study that has enrolled over 6,554 MS patients across 10-sites. Standardized quantitative 3-Tesla brain MRIs, depressive symptoms and clinical information are acquired at least annually as a part of this study. She will test whether longitudinal changes in specific brain substructure volumes are associated with depressive symptom worsening in people with MS (Aim 1). Further, to advance our understanding of plausible, upstream depression risk factors, she will also test if circadian rhythm disruption and sleep disturbance are potential contributors to depression (possibly mediated through alterations to brain structure) in a subset of local MS PATHS participants (n=100; Aim 2). Taken together, findings from these studies will be derived using a powerful longitudinal design and may provide important insight into understanding how depressive symptoms evolve in people with MS. The data and, importantly, the training garnered from the proposed award will allow the candidate to become an independent investigator with the skills needed to conduct high-quality depression research as it relates to people with MS.

项目摘要 此应用程序是一个指导研究科学家职业发展奖（K 01）。该奖项将提供 候选人具有增强的技能和必要的培训，以建立一个研究计划来调查 中枢神经系统（CNS）自身免疫性疾病中抑郁负担增加， 多发性硬化症（MS）患有MS的人患精神病合并症的风险明显更高， 包括抑郁症MS患者中重度抑郁症的终生患病率估计达到50%， 几乎是其他慢性病患者的两倍抑郁症也与MS相关的过度 发病率和死亡率。然而，造成儿童负担增加的具体机制和风险因素， MS中的抑郁症尚未得到很好的理解。建议项目的目标是为候选人提供 建立一个专注于理解神经生物学的独立项目所需的高级技能 MS抑郁症患者的机制，这将更好地为治疗和预防策略提供信息， 风险人群。所提出的综合全面的培训计划结合了正式的课程、教学 她的导师的指导，应用动手数据收集和分析会议，并出席科学 研讨会和会议。主要培训目标包括：1）更深入地了解抑郁症生物学 为了更好地为风险和预防研究提供信息，2）在大规模人群中评估抑郁症的经验- 基于研究的学习，3）应用结构神经影像分析的技能，作为更好地理解 神经解剖学上的变化与抑郁症状有关。其他培训目标包括获得关键的 在MS抑郁症的潜在风险上游风险因素的评估经验。具体来说， 候选人将接受睡眠和昼夜节律生物学的培训和评估，这是两个相关的， 生物学上合理的贡献者抑郁症在MS。这一全面的，复合培训计划将 允许候选人利用现有的数据和基础设施，从一个大型的正在进行的观察性研究， 在10个研究中心招募了超过6，554名MS患者。标准化定量3特斯拉脑MRI，抑郁症 作为本研究的一部分，至少每年采集一次症状和临床信息。她将测试是否 特定脑亚结构体积的纵向变化与抑郁症状恶化相关 MS患者（目标1）。此外，为了促进我们对合理的上游抑郁症风险因素的理解， 她还将测试昼夜节律紊乱和睡眠障碍是否是抑郁症的潜在因素 （可能通过改变大脑结构介导）在当地MS PATHS参与者的子集（n=100; 目标2）。总之，这些研究的结果将使用强有力的纵向设计得出， 提供了重要的见解，了解抑郁症状如何演变的人与MS的数据和， 重要的是，从拟议的奖项获得的培训将使候选人成为一个独立的， 研究人员需要进行高质量的抑郁症研究，因为它涉及到MS的人的技能。