Refining Phenotypic Measures of Nicotine Withdrawal

描述(由申请人提供)： 更好地了解尼古丁戒断的表型特征及其遗传影响可能有助于降低严重依赖和复吸吸烟者的发病率和死亡率。候选人正在申请导师临床科学家发展奖(K08)，以便开发一条独立的研究路线来解决这个严重的问题。私人助理在戒烟研究方面拥有丰富的经验，并努力加强她在统计遗传学和相关量化方法以及烟草使用行为评估方面的培训，并增加她对分子遗传学程序和尼古丁的神经生物学的熟悉。这项研究的目标是在动物和以前的人类研究结果的指导下，利用访谈和实验室测量戒断的负面情绪、积极情绪和身体症状，为遗传学研究开发一种改进的尼古丁戒断评估；并将其应用于遗传关联的病例对照研究。第一阶段将是对现有数据的分析，以确定DSM-IV尼古丁戒断症状的遗传结构，以及在控制了其他精神和社会人口风险因素后，尼古丁戒断与定期吸烟的遗传影响的重叠程度。同时，一项小型实验室研究(N=60)将解决来自更广泛的戒断症状的因素的有效性和短期可靠性。在这些结果的指导下，将在澳大利亚对400例报告戒烟的目标样本和400名对照(根据第一阶段分析进行选择)进行广泛的尼古丁戒断后续评估，已经从这些样本中获得了DMA和DSM-IV基线访谈数据。尼古丁戒断的基线评估将增加关于积极和消极情绪和身体症状减少的可靠和有效的问题。将对三个候选基因(CHRNB2、OPRM1、CHRNA3)进行分型和测试，以确定与消极情绪、积极情绪和身体症状之间的假设差异关联。这项研究和培训计划的长期目标是使申请者在戒烟失败和尼古丁戒断的药物遗传学研究中结合回顾和同期评估(基于实验室和访谈)，为建立独立的研究生涯做好准备。

DESCRIPTION (provided by applicant): A greater understanding of phenotypic characteristics of, and of genetic influences on, nicotine withdrawal may help decrease morbidity and mortality in heavily dependent and relapsing smokers. The Candidate is applying for a Mentored Clinical Scientist Development Award (K08) in order to develop an independent line of research to address this serious problem. The PI has extensive experience in smoking cessation research and seeks to augment her training in statistical genetics and related quantitative methods, and assessment of tobacco use behaviors, and to increase her familiarity with molecular genetics procedures, and the neurobiology of nicotine. The goal of this research is to develop an improved assessment of nicotine withdrawal for genetic research, guided by findings from animal and previous human research, using interview and laboratory measures of negative affect, positive affect, and physical symptoms of withdrawal; and to apply this in a case-control study of genetic association. The first stage will be analysis of existing data, to determine the genetic structure of DSM-IV nicotine withdrawal symptoms, and the degree of overlap of genetic influences on nicotine withdrawal versus regular smoking, after control for other psychiatric and sociodemographic risk factors. Concurrently a small laboratory study (N=60) will address the validity and short-term reliability of factors derived from a more extensive battery of withdrawal symptoms. Guided by these results, an extensive follow-up assessment of nicotine withdrawal will be conducted in Australia of a target sample of 400 cases reporting withdrawal, and 400 controls (selection guided by first stage analyses), from whom DMAs and baseline DSM-IV interview data have already been obtained. The baseline assessment of nicotine withdrawal will be augmented by adding reliable and valid questions about decreases in positive as well as negative affect and physical symptoms. Three candidate genes (CHRNB2, OPRM1, CHRNA3) will be typed and tested for hypothesized differential associations with negative affect versus positive affect versus physical symptoms. The long-term goal of this research and training program is to prepare the applicant to establish an independent research career combining retrospective and contemporaneous assessments, both laboratory-based and interview, in pharmacogenetic research on smoking cessation failure and nicotine withdrawal.