An examination of psychomotor disturbance in current and remitted MDD: An RDoC Study

当前和缓解的 MDD 中精神运动障碍的检查：一项 RDoC 研究

• 批准号: 10374003
• 负责人: VIJAY A MITTAL
• 金额: $ 65万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-08 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10374003
• 关键词: Acute; Agitation; Animals; Area; Basal Ganglia; Behavior; Behavior assessment; Brain; Cellular Phone; Characteristics; Cicatrix; Clinical; Cognitive; Data; Depressed mood; Diagnosis; Diagnostic; Diffusion; Disease; Disease remission; Dyskinetic syndrome; Early Diagnosis; Environment; Exhibits; Fatigue; Functional Magnetic Resonance Imaging; Goals; Grain; Heterogeneity; Human; Individual; Laboratories; Lead; Link; Longitudinal Studies; Major Depressive Disorder; Measurement; Measures; Mediating; Mental Depression; Motor; Movement; National Institute of Mental Health; Parkinson Disease; Patients; Phenotype; Prevention; Process; Public Health; Relapse; Reporting; Research; Research Domain Criteria; Rest; Risk; Role; Schizophrenia; Severities; Signal Transduction; Symptoms; System; Testing; Text Messaging; Time; Work; actigraphy; base; behavior measurement; clinical practice; clinically significant; cost effective; depressive symptoms; follow up assessment; follow-up; graph theory; health economics; innovation; longitudinal design; motor behavior; motor symptom; multimodal neuroimaging; neural circuit; neuromechanism; novel; prospective; recruit; relapse prediction; symptom cluster; symptomatology; tool; treatment response; treatment strategy; white matter

Project Summary Major depressive disorder (MDD) is a serious public health problem that has, at best, modest treatment response. One reason for this mixed efficacy is that MDD has a very heterogeneous clinical presentation. One way to parse the heterogeneity is to investigate the role of particular features of MDD, an endeavor that can also help identify novel and focal targets for treatment and prevention efforts. Psychomotor disturbance (e.g., psychomotor agitation [PmA] and retardation [PmR]) has long been viewed as a particularly pernicious feature of MDD, and yet we know surprisingly little about these behaviors. For example, it is unknown if motor disturbance occurs only in active depression, or whether it also continues into remission (potentially signaling vulnerability for relapse). There also has been little work (a) linking PmA & PmR with abnormal neural circuitry mediating these motor behaviors, (b) examining how motor symptoms change over the course of illness, and (c) investigating whether PmR & PmA represent a single underlying process, or reflect distinct mechanisms. The present proposal seeks to test these questions and also identify powerful and easy to administer tools to assess these behaviors in clinical practice. The proposed project will recruit those with current MDD (n = 100), remitted MDD (n = 100) and controls (n = 50) and take a Research Domain Criteria (RDoC) approach by comparing the three groups on multiple indicators of PmR and PmA (Aim 1). Specifically, we will assess PmR and PmA with self and observer- based reports, behavioral assessments in the laboratory (Velocity Scaling [PmR] and Force Variability [PmA]), and behavioral assessments in subjects' natural environment (actigraphy and daily typing behavior on one's smartphone [texting, emailing, etc.]). These behavioral measures are particularly critical as they yield more fine-grained and objective assessments of PmR and PmA that may be missed by traditional diagnostic assessments. Aim 2 seeks to examine the structural (diffusion tensor) and functional (resting state fMRI) connectivity of motor circuitry of the three groups as well as the relation between motor circuitry and the proposed indicators of PmR and PmA. For this aim, we will utilize innovative graph theory metrics of connectivity of the three primary motor circuits identified in animal and human studies (specifically, basal ganglia, cerebellar and cortico-cortical motor circuits) which will provide a comprehensive examination of motor system organization in MDD. Aim 3 seeks to follow-up subjects three times over 18 months to evaluate whether motor symptoms change in tandem with overall depressive symptoms and functioning over time and/or whether baseline PmR/PmA predicts course of depression an functoining. Aim 3 is particularly clinically significant. Finding that motor and overall depression severity co- vary over time, or that motor variables predict subsequent change in overall depression severity, would support the potential clinical utility of the proposed novel, reliable, and easily administered motor assessments.

项目摘要 重度抑郁障碍(MDD)是一个严重的公共卫生问题，充其量只能得到适度的治疗 回应。这种混合疗效的一个原因是MDD具有非常不同的临床表现。一 解析异构性的方法是调查MDD的特定功能的作用，这一努力可以 还有助于确定治疗和预防工作的新的和重点目标。精神运动障碍(例如， 精神运动激越[PMA]和迟缓[PMR])长期以来一直被视为一种特别有害的特征 但令人惊讶的是，我们对这些行为知之甚少。例如，目前尚不清楚电机是否 干扰只发生在活动性抑郁症中，或者是否也持续到缓解期(潜在的信号 复发的脆弱性)。也很少有工作(A)将PMA和PMR与异常神经回路联系起来 调节这些运动行为，(B)检查运动症状在疾病过程中如何变化，以及 (C)调查PMR和PMA是否代表单一的基本进程，或反映不同的机制。 目前的提案试图测试这些问题，并找出强大和易于管理的 在临床实践中评估这些行为的工具。拟议的项目将招聘那些目前患有MDD的人(n =100)，缓解MDD(n=100)和对照(n=50)，并采用研究领域标准(RDoC)方法 通过比较三组PMR和PMA的多项指标(目标1)。具体地说，我们将评估 PMR和PMA，包括基于自我和观察者的报告、实验室中的行为评估(Velocity 标度[PMR]和力变异性[PMA])，以及受试者自然环境中的行为评估 (智能手机上的动作记录和日常打字行为[短信、电子邮件等])。这些行为 衡量标准尤其关键，因为它们对PMR和PMA做出了更细粒度和更客观的评估 这一点可能会被传统的诊断评估遗漏。目标2试图检查结构(扩散) 张量)和功能(静息状态fMRI)的连通性，以及 电机电路与PMR和PMA拟议指标之间的关系。为此，我们将利用 创新图论度量动物和动物中识别的三个主要马达电路的连通性 人体研究(特别是基底节、小脑和皮质-皮质运动回路)将提供 MDD中运动系统组织的全面检查。目标3寻求跟进主题3 评估运动症状是否与总体抑郁同步变化的时间超过18个月 症状和功能随时间的变化和/或基线PMR/PMA是否预测抑郁症和 工作正常。目标3具有特别重要的临床意义。发现运动和整体抑郁的严重程度共同作用 随着时间的推移而变化，或者运动变量预测总体抑郁严重程度随后的变化，将支持 拟议的新的、可靠的和易于管理的运动评估的潜在临床应用。