Targeting reward dysfunction as a mechanism to improve smoking cessation

将奖励功能障碍作为改善戒烟的机制

基本信息

批准号：
9265051
负责人：
Maggie M Sweitzer
金额：
$ 15.69万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-05-01 至 2021-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9265051
关键词：
Abstinence Academic Medical Centers Aftercare Behavioral Brain Brain region Cause of Death Cessation of life Chronic Cigarette Clinical Clinical Research Clinical Trials Comorbidity Conduct Clinical Trials Corpus striatum structure Cues Data Dependence Development Disease Equilibrium Ethics Evaluation Exhibits Exposure to Functional Magnetic Resonance Imaging Functional disorder Future Goals Hypersensitivity Individual Intervention Knowledge Literature Medial Mediating Mediator of activation protein Mental Depression Mentors Methods Moods Neurosciences Nicotine Nicotine Dependence Outcome Pathway interactions Positioning Attribute Prefrontal Cortex Protocols documentation Psychological reinforcement Randomized Relapse Research Research Methodology Research Personnel Research Training Rewards Severities Smoke Smoker Smoking Smoking Behavior Techniques Theoretical model Time Tobacco Dependence Tobacco smoking Training Translating Withdrawal Withholding Treatment addiction behavioral pharmacology career career development cigarette smoking depressive symptoms design disability effective therapy efficacy study experience improved neuroadaptation neurobehavioral neuroimaging nicotine patch non-drug non-smoking novel psychosocial public health relevance research study response responsible research conduct reward processing skills smoking cessation successful intervention theories therapy design therapy development

项目摘要

DESCRIPTION (provided by applicant): Tobacco smoking remains a leading cause of death and disability in the developed world. Many who wish to quit smoking are unable to do so. Although substantial advances have been made to identify neurobehavioral mechanisms underlying nicotine dependence, there is a great need to translate these findings into targeted, efficacious interventions, and to understand the mechanisms by which successful interventions exert their effects. Theoretical models and a growing empirical literature suggest that addictive disorders, including tobacco dependence, are characterized by mesolimbic hypersensitivity to smoking reward and related cues and hyposensitivity to nonsmoking rewards, particularly during the withdrawal that occurs during the early stages of a quit attempt. This dysregulated reward processing may represent a particular vulnerability for individuals with depressive symptoms that is likely to contribute to relapse and presents a promising target for intervention. The overarching goal of the research proposed in this application is to develop and evaluate a novel intervention that directly targets this reward processing imbalance by both a) decreasing smoking reinforcement through pretreatment with very low nicotine cigarettes (VLNC's) and b) increasing reinforcement from other non-drug rewards through behavioral activation (BA). The proposed research study has the following aims: 1) To examine the effects of BA + VLNC compared with VLNC only on mesolimbic reactivity and subjective sensitivity to smoking and monetary rewards among smokers with mild depressive symptoms; 2) To gather preliminary data on the effects of combined BA + VLNC on smoking cessation outcomes; and 3) To explore mediating and moderating effects of pre-and post-treatment brain function on smoking outcomes. The proposed research builds upon the Principle Investigator, Dr. Maggie Sweitzer's, previous experience and is closely aligned with her overarching career development goal of becoming an independent investigator with expertise in the development and evaluation of mechanistically-informed treatments for smoking cessation. Dr. Sweitzer is a clinical associate at Duke University Medical Center with expertise in behavioral pharmacology of smoking and functional neuroimaging. The primary training goals of this application are to gain skills in a) advanced neuroscience and neuroimaging methods; b) treatment development and evaluation; c) conducting clinical trials; and d) ethical and responsible conduct of research. The results of the proposed research and training plans will facilitate Dr. Sweitzer's development as an independent investigator and provide preliminary data for a future larger scale efficacy study.

描述（由申请人提供）：吸烟仍然是发达国家死亡和残疾的主要原因，尽管在确定尼古丁依赖的神经行为机制方面已经取得了实质性进展，但许多希望戒烟的人却无法戒烟。非常需要将这些发现转化为有针对性的、有效的干预措施，并了解成功干预措施发挥作用的机制。理论模型和越来越多的实证文献表明，包括烟草依赖在内的成瘾性疾病的特点是。中脑边缘对吸烟奖励和相关线索过敏，对非吸烟奖励不敏感，特别是在戒烟尝试的早期阶段发生的戒断过程中，这种失调的奖励处理可能代表了患有抑郁症状的个体的特殊脆弱性，可能导致复发。并提出了一个有希望的干预目标。本申请中提出的研究的总体目标是开发和评估一种新颖的干预措施，通过以下方式直接针对这种奖励处理失衡：a）通过极低的预处理来减少吸烟强化。尼古丁香烟 (VLNC) 和 b) 通过行为激活 (BA) 增加其他非药物奖励的强化拟议的研究有以下目的： 1) 与仅 VLNC 相比，检查 BA + VLNC 对中脑边缘反应性和的影响。患有轻度抑郁症状的吸烟者对吸烟和金钱奖励的敏感性；2) 收集 BA + VLNC 组合对戒烟结果影响的初步数据；3) 探索中介作用；拟议的研究建立在首席研究员 Maggie Sweitzer 博士之前的经验基础上，并且与她成为具有专业知识的独立研究者的总体职业发展目标密切相关。 Sweitzer 博士是杜克大学医学中心的临床助理，具有吸烟行为药理学和功能神经影像方面的专业知识。 a) 先进的神经科学和神经影像学方法；b) 治疗开发和评估；c) 进行临床试验；以及 d) 所提出的研究和培训计划的结果将促进 Sweitzer 博士的发展。独立研究者并为未来更大规模的功效研究提供初步数据。