Nicotine Dependence: Phenotype, Endophenotype & Contexts

这次更新建立在我们当前TTURC主题的基础上，以确定家庭、幼儿和一生 决定吸烟的生物、心理和社会途径：吸烟的终生模式、使用和戒烟以及相关的依赖模式。为此，在过去的4年里，我们实施了一项前瞻性的三代家庭研究，以检查尼古丁依赖的终生途径；b)开发并验证了有前景的新的终生烟草使用和依赖表型评估；c)评估了共病的测量方法。 筛查门槛较低，以包括亚临床病理)，如酒精、精神障碍和气质；以及d)采集血液和唾液样本。我们的TTURC的新英格兰家庭研究(NEFS)：创造了一种强大的跨学科(TD)合作文化。伴随着这一“智力资本”的是来自我们独特的第三代队列的丰富且不断增长的数据库和样本样本库，以及未来科学家蓬勃发展的职业发展站点。我们提出了三项新的Nef研究：1)进行两代人家庭 这些研究包括：1)研究遗传/家庭因素对终生吸烟表型和共病精神疾病的影响；2)对与这些烟草使用表型不一致的同胞对进行内表型研究，包括功能磁共振成像与尼古丁挑战；以及3)研究邻里因素对青少年吸烟、酒精和其他药物使用进展的影响的调节和调节。拥有五个强大的核心和一批精选的新科学家，他们在三个Nefs研究的新内容领域拥有专业知识：神经科学、大脑 影像、行为遗传学、精神疾病、酒精和其他疾病的共同发病率、社会背景、空间相关性，以及措施和方法的发展，这次更新利用了尚未开发的机会来扩大已经积累的丰富数据库。这次续签，正是因为它直接建立在当前的TTURC主题上，为TD合作创造了相当大的机会。这项为期10年的综合研究计划，提供了规模经济和巨大的“增值”潜力，使投资最大化。 已经取得的进展，极大地开拓了新的领域，并确保TD整体大于其各部分之和。

This renewal builds on our current TTURC theme, to identify familial, early childhood and lifetime biopsychosocial pathways that determine: lifetime patterns of smoking uptake, use and cessation and the associated patterns of dependence. To do this, over the past 4 years, we have: a) implemented a prospective, three generation family study to examine the lifetime pathways to nicotine dependence; b) developed and validated promising new lifetime tobacco use and dependence phenotypic assessments; c) assessed measures of comorbidity with lower screening thresholds to include sub-clinical pathology) such as alcohol, psychiatric disorder, and temperament; and d) collected blood and saliva specimens. Our TTURC's New England Family Study (NEFS) has :reated a strong culture of transdisciplinary (TD) collaboration. Along with this "intellectual capital" is a rich and growing data-base and specimen sample repository from our unique 3 generation cohort, and a thriving career development site for future scientists. We propose 3 new NEFS studies to: 1) conduct a two-generation family study of genetic/familial influences on lifetime patterns of tobacco use phenotypes and comorbid psychiatric disorders; 2) conduct an endophenotypic study of sib pairs discordant for these tobacco use phenotypes, involving fMRI with nicotine challenge; and 3) examine mediation and moderation of the influence of neighborhood factors ion the progression of tobacco use, alcohol and other drug use in adolescents. With five strong Cores and a select Igroup of new scientists with expertise in the new content areas of the three NEFS studies: neuroscience, brain imaging, behavioral genetics, the co-morbidity of psychiatric, alcohol and other conditions, social context, spatial correlation, as well as measures and methods development, this renewal capitalizes on untapped opportunities to expand the rich database already accumulating. This renewal, precisely because it builds directly on the current TTURC theme, creates considerably greater opportunities for TD collaboration. The consolidated 10-year research program, provides an economy of scale with enormous "value added" potential to maximize the investments already made, significantly break new ground, and ensure that the TD whole is greater than the sum of its parts.