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Dopamine Enhancement of fear extinction learning in PTSD

多巴胺增强 PTSD 患者的恐惧消退学习

基本信息

批准号：
9447442
负责人：
Joshua M Cisler
金额：
$ 32.83万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-03-07 至 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9447442
关键词：
Acute Adult Animals Basic Science Behavior Benserazide Biological Neural Networks Brain Chronic Clinical Clinical Trials Code Cognition Combined Modality Therapy Comorbidity Corpus striatum structure Cues DRD1 gene Development Diagnosis Dopamine Dose Emotional Enzymes Exhibits Exposure to Extinction (Psychology)Fright Functional Magnetic Resonance Imaging Generic Drugs Genes Genetic Genetic Polymorphism Genetic Variation Genotype Goals Human Impairment Individual Individual Differences Ingestion Knowledge Laboratories Lead Learning Levodopa Measures Mediating Memory Mental disorders Modeling Oral Outcome Study Patient Self-Report Pharmacology Phase Placebos Post-Traumatic Stress Disorders Protocols documentation Psychophysiology Public Health Quality of life Regulation Research Research Support Rest Role Sampling Signal Transduction Source Testing Therapeutic Translating Trauma Treatment Efficacy Treatment outcome Violence Vulnerable Populations Woman assault base clinical efficacy conditioned fear dopamine system genetic predictors improved indexing learning extinction neuroimaging neurotransmission novel physical assault psychologic public health relevance receptor relating to nervous system response sex sexual assault success therapy outcome transmission process

项目摘要

DESCRIPTION (provided by applicant): This R21/R33 application in response to RFA-MH-15-300 seeks to demonstrate target engagement and clinical viability for a novel combination therapy for Posttraumatic Stress Disorder. PTSD is associated with poor quality of life and comorbidity with both physical and mental illness. While exposure-based psychological treatments have proven efficacious, up to 40% retain PTSD diagnoses following treatment. Thus, new protocols to boost treatment efficacy can have a significant public health impact. Recent basic research suggests that consolidation of fear extinction learning memories is at least partly dopamine-mediated and that boosting dopamine signaling in the consolidation window can decrease fear responding during subsequent exposure to fear cues. The overall goal of the proposed project is to demonstrate the viability of boosting dopamine signaling in the post-learning consolidation window as a novel means of boosting therapy outcomes among adult women with PTSD related to assaultive violence (physical or sexual assault). In the R21 target engagement phase, we will test the impact of endogenous and exogenous manipulations of dopamine neurotransmission on 1) acute functional organization of dopaminergic resting-state networks, and 2) the consolidation of generic (i.e., laboratory-induced) fear extinction learning using concurrent neuroimaging, psychophysiological, and self-report assessments among women with PTSD (Aim 1). In the R33 clinical phase, we seek to replicate and extend target engagement to the clinical context of fear extinction learning for ideographic trauma memories and emotional responding to trauma cues among women with PTSD using concurrent neuroimaging, psychophysiological, and self-report assessments (Aim 2). Successful demonstration of target engagement (Aim 1) and efficacy for the clinical target of trauma memories and emotional responding to trauma cues (Aim 2) would provide critical scientific support of the viability of combining exposure-based therapy with pharmacological agents that boost dopamine signaling as a means to improve treatment outcomes for PTSD.