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).

项目总结

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