EEG & Behavioral Predictors of Changes in Smoking Trajectories in Young Light Smo

描述(由申请人提供)：该建议是在纵向设计中识别128名年轻轻度吸烟者(YL)吸烟率和尼古丁依赖变化的大脑、行为和自我报告预测因素，使用一些新的预测因素，包括脑电的个体差异(ID)和基线以及对标准化和自我选择的急性尼古丁剂量(ANIC)的反应。α5尼古丁受体亚单位中一个引人注目的遗传功能变异多态rs16969968的关联也将与吸烟进展和ANIC反应有关。预测因素将是通过大脑(大脑皮层)、行为和自我报告指数评估的注意力、情感和与奖励相关的过程，这些指数在尼古丁依赖(ND)吸烟者中被很好地验证为对ANIC的反应。证据表明，对第一次吸烟的初始反应，从轻度吸烟到规律吸烟，以及进展到ND，都受到遗传和环境因素的影响。有充分的理由假设，在ANIC对YLS的注意力、情绪和大脑反应性的影响中更好地表征IDs将为YLS中有助于强化吸烟和吸烟轨迹的机制提供重要的见解。这些信息可能导致针对高危YLS的有针对性的药物治疗和行为干预。以下假设将在YLS人群中进行检验：1)ANIC将通过情绪负面的图片和文字提高注意力表现、情绪和抵抗分心，这些有益的(强化)效应将预测3、6、12和18个月后吸烟率的变化；2)较低的基线注意力和情绪水平将预测后续吸烟的更大增加。3)皮层(脑电、事件相关电位和来源定位分析)指数低的脑电活动(高θ和α功率)，P3b波幅降低，负价干扰物对靶P3b的更大降低将预测尼古丁剥夺状态下吸烟增加；4)即使在控制了可能促进吸烟变化的社会因素后，假设1-3仍将得到支持。二次探索性分析将包括Alpha5-Alpha3-Beta4尼古丁受体基因簇的功能变异多态rs16969968与吸烟变化和其他变化预测因素的关系，包括对ANIC的反应。

DESCRIPTION (provided by applicant): The proposal is to identify brain, behavioral, and self-report predictors of progression to changes in smoking rate and nicotine dependence in 128 young light smokers (YLS) in a longitudinal design using a number of novel predictors, including individual differences (IDs) in EEG and reward sensitivity at baseline and in response to standardized and to self-selected acute nicotine doses (ANIC). The associations of a compelling genetic functional variant polymorphism, rs16969968, in the alpha5 nicotinic receptor subunit will also be related to smoking progression and ANIC responses. The predictors will be attentional, affective, and reward-related processes assessed with brain (electrocortical), behavioral, and self-report indices that are well validated as responsive to ANIC in nicotine-dependent (ND) smokers. Evidence indicates that initial responses to first smoking experience, progression from light to regular smoking, and progression to ND are influenced by both genetic and environmental factors. There is good reason to hypothesize that better characterization of IDs in the effects of ANIC on attention, mood, and brain reactivity in YLS will provide important insights into mechanisms that contribute to the reinforcement of smoking and smoking trajectories in YLS. Such information could lead to targeted pharmacotherapy and behavioral interventions for at-risk YLS. The following hypotheses would be tested in a population of YLS: 1) ANIC will increase attention performance, mood, and resistance distraction by emotionally negatively valent pictures and words and that these beneficial (reinforcing) effects will predict changes in smoking rate 3, 6, 12, and 18 months later, 2) Lower baseline attentional and emotional levels will predict greater increases in smoking at the follow-ups. 3) Electrocortical (EEG, ERP, and source localization analyses) indices of low EEG activity (high theta & alpha power), reduced P3b amplitude, and greater reductions in P3b to targets following negatively valent distractor will predict increased smoking during nicotine deprived states and 4) hypotheses 1-3 will be supported even after controlling for social factors that may promote change in smoking. Secondary exploratory analyses will include the relationships of the functional variant polymorphism rs16969968 of the alpha5-alpha3-beta4 nicotinic receptor gene cluster to changes in smoking and to other predictors of change, including responses to ANIC.