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: 9754473
• 负责人: VIJAY A MITTAL
• 金额: $ 76.76万
• 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/9754473
• 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; Structure; Symptoms; System; Testing; Text; 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 symptom; multimodality; neural circuit; neuroimaging; 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 重度抑郁症（MDD）是一个严重的公共卫生问题，最多只能得到适度的治疗 反应这种混合疗效的一个原因是MDD具有非常异质的临床表现。一 解析异构性的一种方法是研究MDD的特定特性的作用，这种奋进可以 还有助于确定治疗和预防工作的新的重点目标。精神障碍（例如， 精神激动[PmA]和迟滞[PmR]）长期以来一直被视为一种特别有害的特征 但我们对这些行为知之甚少。例如，不知道发动机是否 干扰只发生在活动性抑郁症，或者它是否也持续到缓解（潜在的信号 易复发）。也有很少的工作（a）连接PmA和PmR与异常的神经回路 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，和 (c)研究PmR和PmA是否代表一个单一的潜在过程，或反映不同的机制。 目前的建议旨在测试这些问题，并确定强大的和易于管理的 在临床实践中评估这些行为的工具。拟议项目将招募当前MDD（n = 100）、缓解MDD（n = 100）和对照组（n = 50），并采用研究领域标准（RDoC）方法 比较三组PmR和PmA的多项指标（目的1）。具体而言，我们将评估 PmR和PmA与自我和基于观察者的报告，实验室行为评估（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 （活动记录和智能手机上的日常打字行为[发短信，发电子邮件等]）。这些行为 这些指标尤其重要，因为它们可以对PmR和PmA进行更细粒度和更客观的评估 这可能被传统的诊断方法所忽略。目标2旨在检查结构（扩散 张量）和功能（静息状态fMRI）连接的运动电路的三个组，以及 运动电路与PmR和PmA的建议指标之间的关系。为此，我们将利用 在动物和哺乳动物中识别的三个主要运动回路连通性的创新图论指标 人类研究（特别是基底神经节、小脑和皮质-皮质运动回路）， MDD患者运动系统组织的全面检查。目标3寻求对主题三采取后续行动， 时间超过18个月，以评估运动症状的变化是否与整体抑郁症 随着时间的推移，症状和功能和/或基线PmR/PmA是否预测抑郁症的病程， functoining。目标3在临床上尤其重要。发现运动和整体抑郁症的严重程度- 随着时间的推移而变化，或者运动变量预测整体抑郁严重程度的后续变化，将支持 所提出的新颖、可靠且易于管理的运动评估的潜在临床效用。