Development of A Novel Transdiagnostic Intervention for Anhedonia

开发一种针对快感缺失的新型跨诊断干预措施

• 批准号: 9456980
• 负责人: GABRIEL S DICHTER
• 金额: $ 19.83万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-01 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9456980
• 关键词: Achievement; Aftercare; Amygdaloid structure; Anhedonia; Anterior; Anxiety Disorders; Applications Grants; Attention deficit hyperactivity disorder; Behavior; Behavioral; Brain; Clinic; Clinical; Clinical Research; Clinical Trials; Communities; Corpus striatum structure; Data; Development; Disease; Dose; Exhibits; Functional Magnetic Resonance Imaging; Funding; Future; Goals; Human Subject Research; Impairment; Incentives; Individual; Intervention; Investigational Therapies; Measures; Mediating; Mental disorders; Mood Disorders; Motivation; National Institute of Mental Health; Neurobiology; Outcome; Outcome Measure; Outpatients; Patient Care; Pharmacological Treatment; Phase; Phenotype; Policies; Positive Valence; Prefrontal Cortex; Psychiatry; Public Health; Research; Research Domain Criteria; Research Project Grants; Rewards; Sampling; Scanning; Schizophrenia; Services; Specificity; Standardization; Stimulus; Substance Use Disorder; Symptoms; System; Testing; Translations; United States Agency for Healthcare Research and Quality; United States National Institutes of Health; Ventral Tegmental Area; Work; avoidance behavior; blood oxygen level dependent; caudate nucleus; cingulate cortex; clinical practice; data sharing; design; endophenotype; expectation; functional MRI scan; functional outcomes; improved; indexing; motivated behavior; neuroimaging; novel; pleasure; psychiatric symptom; psychosocial; relating to nervous system; response; reward anticipation; reward processing; therapy development; treatment duration; treatment effect

Project Summary Deficits in motivation and pleasure, together referred to as anhedonia, are implicated in a number of psychiatric illnesses, including mood and anxiety disorders, substance-use disorders, schizophrenia, and attention- deficit/hyperactivity disorder. As a result, constructs related to anhedonia are central to the NIMH Research Domain Criteria (RDoC) project. Anhedonia is often one of the most difficult psychiatric symptoms to treat and thus represents a critical endophenotype and vulnerability factor for a range of psychiatric disorders. Given the centrality of anhedonia to a large number of psychiatric disorders, improved interventions to treat motivation and pleasure are critical for these disorders. The overall goal of this R61/R33 project is to develop a novel transdiagnostic treatment for anhedonia, called Behavioral Activation Treatment for Anhedonia (BATA). This new intervention is designed to treat anhedonia by emphasizing supported engagement with personally relevant goals and reducing avoidance behaviors. Consistent with the objectives and milestones outlined in RFA-MH-16-406 (“Exploratory Clinical Trials of Novel Interventions for Mental Disorders”), in the R61 phase of this trial we propose to use an experimental therapeutics approach to first evaluate mesocorticolimbic target engagement by this treatment in a transdiagnostic sample characterized by clinically impairing anhedonia (Aim 1). Specifically, we will examine the effects of this treatment, relative to an active comparison treatment, on caudate nucleus activation during reward anticipation and rostral anterior cingulate cortex activation during reward outcomes using ultra-high field (7T) functional magnetic resonance imaging. In this phase of the project, we will also use fMRI to determine the optimal dose of the intervention (Aim 2). If quantitative milestones for target engagement are achieved, in the R33 phase of this proposal we plan to evaluate the effects of the optimal does of this new treatment, versus an active comparison treatment, on anhedonic symptoms and functional outcomes (Aim 3), behavioral indicators of reward sensitivity (Aim 4), and neural indicators of reward processing (Aim 5). If hypotheses are supported, the results of this project will change real-world clinical practice given that there are currently no empirically-validated treatments, psychosocial or otherwise, that target anhedonia transdiagnostically. Given the high rates of clinically impairing anhedonia across a range of psychiatric disorders, as well as the relative ease with which BATA can be disseminated, this novel intervention has the potential to rapidly and meaningfully impact patient care in clinics that specialize in a range of disorders and conditions, including mood disorder clinics, anxiety disorder clinic, and general outpatient psychiatry services. The application proposed here cuts across multiple NIMH priorities and initiatives, including an experimental therapeutics approach to treatment development (NOT-MH-14-007: Policy for Submission of Applications Containing Clinical Trials), the use of standardized phenotype measures (NOT- MH-15-009: Data Harmonization for NIMH Human Subjects Research via the PhenX Toolkit), rigor and transparency in research (NOT-OD-16-011: Rigor and Transparency in NIH & AHRQ Research Grant Applications), and data sharing with the scientific community (NOT-MH-14-015: Data Sharing Expectations for NIMH-funded Clinical Trials and NOT-MH-15-012: Data Sharing Expectations for Clinical Research Funded by NIMH).

项目概要 动机和快乐的缺陷，统称为快感缺失，与许多精神疾病有关。 疾病，包括情绪和焦虑障碍、物质使用障碍、精神分裂症和注意力障碍 缺陷/多动症。因此，与快感缺失相关的构建是 NIMH 研究的核心 领域标准 (RDoC) 项目。快感缺乏通常是最难治疗和治疗的精神症状之一 因此代表了一系列精神疾病的关键内表型和脆弱性因素。鉴于 快感缺失是许多精神疾病的核心，改进治疗动机的干预措施 和快乐对于这些疾病至关重要。 R61/R33 项目的总体目标是开发一种新颖的 针对快感缺失的跨诊断治疗，称为快感缺乏行为激活治疗 (BATA)。这 新的干预措施旨在通过强调支持性的个人参与来治疗快感缺失 相关目标并减少回避行为。与中概述的目标和里程碑一致 RFA-MH-16-406（“精神障碍新型干预措施的探索性临床试验”），处于 R61 阶段 在这项试验中，我们建议使用实验性治疗方法来首先评估中皮质边缘靶标 在以临床快感缺失受损为特征的跨诊断样本中采用这种治疗方法（目标 1）。具体来说，我们将检查这种治疗相对于积极的比较治疗的效果， 奖励预期过程中尾状核的激活和奖励预期过程中前扣带皮层的激活 使用超高场 (7T) 功能磁共振成像奖励结果。在这个阶段的 项目中，我们还将使用功能磁共振成像来确定干预的最佳剂量（目标 2）。如果定量的话 目标参与的里程碑已经实现，在本提案的 R33 阶段，我们计划评估 与积极的比较治疗相比，这种新治疗的最佳剂量对快感缺失的影响 症状和功能结果（目标 3）、奖励敏感性的行为指标（目标 4）和神经 奖励处理指标（目标 5）。如果假设得到支持，该项目的结果将会改变 鉴于目前没有经过经验验证的治疗方法、心理社会或 否则，就会跨诊断地针对快感缺失。鉴于临床上快感缺失的发生率很高 涵盖一系列精神疾病，以及传播 BATA 相对容易，这 新颖的干预措施有可能迅速而有意义地影响专门从事特定领域的诊所的患者护理 一系列疾病和病症，包括情绪障碍诊所、焦虑症诊所和一般疾病 门诊精神病学服务。这里提出的应用程序跨越多个 NIMH 优先事项，并且 倡议，包括治疗开发的实验性治疗方法（NOT-MH-14-007：政策 用于提交包含临床试验的申请），使用标准化表型测量（NOT- MH-15-009：通过 PhenX 工具包进行 NIMH 人类受试者研究的数据协调）、严谨性和 研究透明度（NOT-OD-16-011：NIH 和 AHRQ 研究资助的严格性和透明度 应用程序），以及与科学界的数据共享（NOT-MH-14-015：数据共享期望 NIMH 资助的临床试验和 NOT-MH-15-012：对资助的临床研究的数据共享期望 镍氢金属研究所）。