NICOTINE DEPENDENCE: RISK & RECOVERY OVER GENERATIONS

产品说明：（申请人的描述）本TTURC的总体目标是确定决定以下因素的家族性、幼儿期和终生精神因素：从吸烟开始到依赖的发展轨迹;终生吸烟模式;戒烟的自然过程;以及对治疗的反应。我们提出的研究计划结合了治疗/预防的必要性，遗传流行病学方法和寿命发展的角度，共享共同的科学资源，以推进人类尼古丁依赖的研究，从基本机制到应用干预。我们将使用基于社区的样本，前瞻性设计和多代家庭研究的协同组合来研究尼古丁依赖的主要途径，并开发和验证烟草使用和尼古丁依赖表型的寿命分类。主要目标是确定可改变的风险因素，这些因素可以作为预防目标，并可以用来提高吸烟预防和戒烟治疗的成功率。我们认识到，许多这样的可改变的风险因素可能会采取行动，在音乐会或对基板的遗传风险，和理由，一个相结合的环境和遗传/家族的策略，需要明确识别突出的环境因素，并准备研究易感基因。为此，我们建议：l）整合多学科视角和研究方法，从基础科学到应用，包括（a）纵向自然历史研究（发育流行病学）;（B）家族聚集方法（遗传流行病学）;（c）人类实验室研究;和（d）干预试验;（2）采用这种寿命和跨代遗传流行病学方法，以帮助了解以下情况的风险因素和因果途径：（B）成人吸烟模式;（c）戒烟的自然过程;及（d）对治疗的反应;（3）记录针对吸烟者风险状况的持续“护理管理”方法治疗吸烟者的潜在效用和成本效益（从相对不复杂到多种合并症），有一系列治疗方案，这些方案沿着干预强度和方式方面各不相同;（4）收集和保存DNA，期望在改进表型定义后，表征候选基因，（在其他样本中），并确定最可遗传的吸烟行为形式，我们可以提供信息并实施有效和富有成效的策略来识别尼古丁依赖的易感基因。

DESCRIPTION: (Applicant's Description) The overall aim of this TTURC is to identify familial, early childhood and lifetime psychiatric factors that determine: trajectories of progression from smoking initiation to dependence; lifetime smoking patterns; the natural course of cessation; and response to treatment. Our proposed program of research combines a treatment/prevention imperative, a genetic epidemiologic approach, and a lifespan developmental perspective, sharing common scientific resources, to advance research on human nicotine dependence from basic mechanisms to applied interventions. We will use a synergistic combination of a community-based sample, prospective design, and a multigenerational family study to examine the major pathways to nicotine dependence, and to develop and validate a lifespan taxonomy of tobacco use and nicotine dependence phenotypes. The major goal is to identify modifiable risk factors that can serve as targets for prevention and that may be harnessed to enhance smoking prevention and cessation treatment success. We recognize that many such modifiable risk factors may act in concert with or against a substrate of genetic risks, and reason that a combined environmental and genetic/familial strategy is required both to clearly identify salient environmental agents and to prepare for studies of susceptibility genes. To this end, we propose to: l) To integrate multiple disciplinary perspectives and research methods front basic science to applications including (a) longitudinal natural history research (developmental epidemiology); (b) familial aggregation methods (genetic epidemiology); (c) human laboratory studies; and (d) intervention trials; (2) To adopt this lifespan and transgenerational genetic epidemiological approach to help understand risk factors for and causal pathways of: (a) progression of nicotine dependence among youth; (b) patterns of adult smoking; (c) the natural course of smoking cessation; and (d) response to treatment; (3) To document the potential utility and cost-effectiveness of a sustained "care management" approach to treating smokers that addresses smokers' risk profiles (from relatively uncomplicated to multiple comorbidities) with a range of treatment options that vary along dimensions of intensity and modality of intervention; (4) To collect and preserve DNA with the anticipation that, after refining phenotypic definitions, characterizing candidate genes (in other samples), and identifying the most heritable forms of smoking behavior, we may inform and conduct an efficient and productive strategy to identify susceptibility genes for nicotine dependence.