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和遗传影响可能有助于降低重度依赖和复发吸烟者的发病率和死亡率。候选人正在申请指导临床科学家发展奖（K 08），以开发一个独立的研究路线，以解决这一严重问题。PI在戒烟研究方面拥有丰富的经验，并寻求加强她在统计遗传学和相关定量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神经生物学的熟悉程度。本研究的目标是在动物和先前人类研究结果的指导下，使用访谈和实验室测量的负面影响，积极影响和戒断的身体症状，为遗传研究开发尼古丁戒断的改进评估;并将其应用于遗传关联的病例对照研究。第一阶段将分析现有数据，以确定DSM-IV尼古丁戒断症状的遗传结构，以及在控制其他精神和社会人口学风险因素后，尼古丁戒断与常规吸烟的遗传影响重叠程度。同时，一项小型实验室研究（N=60）将探讨从更广泛的戒断症状组合中得出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例报告戒断的目标样本和400例对照（根据第一阶段分析进行选择）进行尼古丁戒断的广泛随访评估，并已从这些对照中获得DMA和基线DSM-IV访谈数据。尼古丁戒断的基线评估将通过增加关于积极和消极影响以及身体症状减少的可靠和有效问题来增强。三个候选基因（CHRNB 2，OPRM 1，CHRNA 3）将被分型和测试的假设差异关联与消极影响与积极影响与身体症状。本研究和培训计划的长期目标是使申请人做好准备，在戒烟失败和尼古丁戒断的药物遗传学研究中，建立一个独立的研究生涯，结合回顾性和同期评估，包括基于实验室的评估和访谈。

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.