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: 10224009
• 负责人: GABRIEL S DICHTER
• 金额: $ 72.57万
• 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 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10224009
• 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; PhenX Toolkit; 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 harmonization; data sharing; design; endophenotype; expectation; functional MRI scan; functional outcomes; improved; indexing; motivated behavior; neuroimaging; novel; optimal treatments; pleasure; psychiatric symptom; psychosocial; relating to nervous system; response; reward anticipation; reward processing; therapy development; treatment comparison; 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 在许多精神病学中实施了动机和愉悦的赤字，共同被称为anhedonia 疾病，包括情绪和焦虑症，药物使用障碍，精神分裂症和注意力 - 赤字/多动症障碍。结果，与Anhedonia相关的结构是NIMH研究的核心 域标准（RDOC）项目。 Anhedonia通常是治疗和治疗的最困难的精神病症状之一 因此，代表了一系列精神疾病的关键内表型和脆弱因素。鉴于 Anhedonia的中心地位对大量的精神疾病，改进了干预措施以治疗动机 愉悦对这些疾病至关重要。这个R61/R33项目的总体目标是开发一部小说 对抗抗衰果的转诊治疗，称为Anhedonia（BATA）的行为激活治疗。这 新的干预旨在通过强调支持个人参与来治疗Anhedonia 相关目标并减少回避行为。与概述的目标和里程碑一致 RFA-MH-16-406（“精神疾病的新干预措施的探索性临床试验”），在R61阶段 我们建议使用实验疗法的方法首先评估中皮质细胞靶标 这种治疗的参与参与以临床上损害抗甲菌的特征的经诊断样本（AIM） 1）特别是，我们将研究这种处理的影响，相对于主动比较处理， 在预期奖励期间和鼻子前扣带回皮层激活期间的尾核激活期间 使用超高场（7T）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fMRI来确定干预的最佳剂量（AIM 2）。如果定量 实现了目标参与的里程碑，在本提案的R33阶段，我们计划评估 这种新处理的最佳作用，而不是主动比较处理对Anhedonic的影响 症状和功能结果（AIM 3），奖励灵敏度的行为指标（AIM 4）和中性 奖励处理的指标（目标5）。如果支持假设，该项目的结果将会改变 鉴于目前尚无经验验证的治疗，社会心理或 否则，该靶向不诊所的靶向。鉴于临床上的Anhedonia的率很高 在一系列精神疾病中，以及Bata传播的相对轻松性， 新颖的干预措施有可能快速而有意义地影响专门研究诊所的患者护理 疾病和病情范围，包括情绪障碍诊所，焦虑症诊所和一般 门诊精神病学服务。此处提出的申请涉及多个NIMH优先级，并且 倡议，包括治疗开发的实验疗法方法（非MH-14-007：政策 为了提交包含临床试验的申请），使用标准化表型措施（非 MH-15-009：NIMH人类受试者通过苯苯式工具包研究的数据协调），严格和 研究的透明度（NOT-OD-16-011：NIH＆AHRQ研究赠款的严格和透明度 应用程序）以及与科学界的数据共享（不是MH-14-015：数据共享期望 NIMH资助的临床试验和非MH-15-012：对临床研究的数据共享期望。 nimh）。

项目成果

Parsing within & between-person dynamics of therapy homework completion and clinical symptoms in two cognitive behavioral treatments for adults with anhedonia.

解析内

• DOI: 10.1016/j.brat.2023.104322
• 发表时间: 2023
• 期刊: Behaviour research and therapy
• 影响因子: 4.1
• 作者: Cernasov,PaulM;Kinard,JessicaL;Walsh,Erin;Kelley,Lisalynn;Phillips,Rachel;Pisoni,Angela;Arnold,Macey;Lowery,SarahC;Ammirato,Marcy;Nagy,GabrielaA;Oliver,JasonA;Haworth,Kevin;Daughters,StaceyB;Dichter,GabrielS;Smoski,Mori
• 通讯作者: Smoski,Mori

Reward Network Modulation as a Mechanism of Change in Behavioral Activation.

• DOI: 10.1177/0145445518805682
• 发表时间: 2020-03
• 期刊: Behavior modification
• 影响因子: 2.3
• 作者: Nagy GA;Cernasov P;Pisoni A;Walsh E;Dichter GS;Smoski MJ
• 通讯作者: Smoski MJ