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

描述（由申请人提供）：该提案是在纵向设计中使用一些新的预测因子，包括脑电图的个体差异（id）和基线时的奖励敏感性，以及对标准化和自选急性尼古丁剂量（ANIC）的反应，确定128名年轻轻度吸烟者（YLS）的吸烟率和尼古丁依赖变化进展的大脑、行为和自我报告预测因子。α - 5烟碱受体亚基中令人信服的遗传功能变异多态性rs16969968的关联也将与吸烟进展和ANIC反应有关。预测因素将是注意力、情感和奖励相关的过程，通过大脑（电皮层）、行为和自我报告指数进行评估，这些指标已被证实对尼古丁依赖（ND）吸烟者的ANIC有反应。有证据表明，首次吸烟的初始反应、从轻度吸烟发展到经常吸烟以及发展为ND受到遗传和环境因素的影响。我们有充分的理由假设，更好地表征ic对YLS中注意力、情绪和大脑反应性的影响，将为YLS中吸烟和吸烟轨迹的强化机制提供重要的见解。这些信息可能导致针对高危YLS的靶向药物治疗和行为干预。以下假设将在YLS人群中进行测试：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（强化）效应将预测3、6、12和18个月后吸烟率的变化；2)较低的注意力和情绪基线水平将预测随访时吸烟的增加。3)皮层电（EEG、ERP和源定位分析）低脑电图活动（高θ和α功率）、P3b振幅降低以及负价分心物对目标P3b的更大减少指标可以预测尼古丁剥夺状态下吸烟的增加，4)假设1-3即使在控制了可能促进吸烟改变的社会因素后也将得到支持。二次探索性分析将包括α 5- α 3- β 4烟碱受体基因簇的功能变异多态性rs16969968与吸烟变化和其他变化预测因子的关系，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.