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).

项目摘要 动机和快乐的缺陷，一起被称为快感缺失，与许多精神疾病有关。 疾病，包括情绪和焦虑症、物质使用障碍、精神分裂症和注意力- 缺陷/多动症。因此，与快感缺失相关的结构是NIMH研究的核心 域标准（RDoC）项目。快感缺失通常是最难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在表型和脆弱性因素。鉴于 快感缺乏是大量精神疾病的中心，改善了治疗动机的干预措施 和快乐是这些疾病的关键这个R61/R33项目的总体目标是开发一种新的 这是一种用于快感缺失的跨诊断治疗，称为快感缺失行为激活治疗（BATA）。这 一种新的干预措施旨在通过强调支持个人参与来治疗快感缺乏症。 相关目标和减少回避行为。与 RFA-MH-16-406（“精神障碍新型干预措施的探索性临床试验”），在R61阶段， 本试验我们建议使用实验治疗方法，首先评估中皮质边缘靶点， 通过这种治疗在以临床损害性快感缺失为特征的转诊断样本中的参与（Aim 1）。具体而言，我们将检查这种治疗相对于活性对照治疗对以下方面的影响： 奖赏预期时尾状核的激活和 使用超高场（7 T）功能磁共振成像的奖励结果。在这个阶段， 项目，我们还将使用功能性磁共振成像来确定干预的最佳剂量（目标2）。如果定量 在本提案的R33阶段，我们计划评估 与活性对照治疗相比，这种新治疗的最佳剂量对快感缺乏的影响 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，本项目的结果将发生变化 考虑到目前还没有经过临床验证的治疗方法， 否则，就以快感缺失为目标进行反诊断。鉴于临床上损害性快感缺失的高发生率 在一系列精神疾病中，以及BATA传播的相对容易性， 新的干预措施有可能迅速和有意义地影响诊所的病人护理， 一系列的疾病和条件，包括情绪障碍诊所，焦虑症诊所，和一般 精神病门诊服务。这里提出的应用程序跨越多个NIMH优先级， 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（非- MH-15-009：通过PhenX工具包的NIMH人类受试者研究的数据协调），严谨性和 研究的透明度（NOT-OD-16-011：NIH和AHRQ研究资助的严格性和透明度 应用），以及与科学界的数据共享（NOT-MH-14-015： NIMH资助的临床试验和NOT-MH-15-012：资助的临床研究的数据共享期望 NIMH）。