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

• 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
• 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

 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(申请人提供)：在发达国家，吸烟仍然是导致死亡和残疾的主要原因。许多想戒烟的人都做不到。尽管在识别尼古丁依赖的神经行为机制方面取得了实质性进展，但仍有必要将这些发现转化为有针对性的、有效的干预措施，并了解成功的干预措施发挥作用的机制。理论模型和越来越多的经验文献表明，包括烟草依赖在内的成瘾障碍的特征是中脑边缘对吸烟奖励和相关线索的高敏感性，以及对非吸烟奖励的低敏感性，特别是在戒烟尝试的早期阶段。对于有抑郁症状的个体来说，这种失调的奖励处理可能代表着一种特殊的脆弱性，可能会导致复发，并提供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的干预措施，通过a)通过使用非常低的尼古丁香烟(VLNC‘s)来减少吸烟强化，以及b)通过行为激活(BA)来增加来自其他非药物奖励的强化，从而直接针对这种奖励处理失衡。建议的研究目的如下：1)比较BA+VLNC与VLNC对轻度抑郁症状吸烟者的中脑边缘反应性、对吸烟的主观敏感性和金钱奖励的影响；2)收集关于BA+VLNC联合治疗对戒烟结果影响的初步数据；以及3)探讨治疗前后脑功能对吸烟结果的中介和调节作用。这项拟议的研究建立在首席调查员玛吉·斯威策博士之前的经验基础上，并与她的总体职业发展目标密切相关，即成为一名独立调查员，拥有开发和评估机械知情戒烟疗法的专业知识。斯威策博士是杜克大学医学中心的临床助理，擅长吸烟的行为药理学和神经功能成像。该应用程序的主要培训目标是获得以下方面的技能：a)先进的神经科学和神经成像方法；b)治疗开发和评估；c)进行临床试验；d)进行合乎道德和负责任的研究。拟议的研究和培训计划的结果将促进Sweitzer博士作为独立研究员的发展，并为未来更大规模的疗效研究提供初步数据。