Nicotine Dependence: Phenotype, Endophenotype & Contexts

这种更新建立在我们目前的TTURC主题，以确定家庭，幼儿和终身 生物心理社会途径决定：吸烟、使用和戒烟的终生模式以及相关的依赖模式。为了做到这一点，在过去的4年里，我们：a）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）开发并验证了有前途的新的终生烟草使用和依赖表型评估; c）评估了合并症的措施， 具有较低的筛选阈值以包括亚临床病理学），例如酒精、精神障碍和气质;和d）收集的血液和唾液样本。我们的TTURC的新英格兰家庭研究（NEFS）：创造了跨学科（TD）合作的强大文化。沿着这一“智力资本”的是我们独特的三代人的丰富和不断增长的数据库和标本样本库，以及为未来科学家提供的蓬勃发展的职业发展网站。我们提出了3个新的NEFS研究：1）进行两代家庭 研究遗传/家族对烟草使用表型和共病精神障碍的终生模式的影响; 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，包括尼古丁激发的fMRI; 3）检查邻居因素对青少年烟草使用、酒精和其他药物使用进展的影响的中介和调节作用。拥有五个强大的核心和一组精选的新科学家，他们在三个NEFS研究的新内容领域具有专业知识：神经科学，大脑 影像学、行为遗传学、精神病、酒精和其他疾病的共病、社会背景、空间相关性以及措施和方法的发展，这一更新利用了尚未利用的机会，扩大了已经积累的丰富数据库。正是因为它直接建立在当前TTURC主题的基础上，所以这次更新为TD合作创造了更多的机会。综合10年的研究计划，提供了一个规模经济与巨大的“增值”潜力，以最大限度地提高投资 在已经取得的成就中，显著地开辟了新的领域，并确保TD整体大于其部分之和。

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.