Genetic Moderation of Attentional Deficits Resulting from Nicotine Withdrawal

尼古丁戒断引起的注意力缺陷的遗传调节

• 批准号: 7706832
• 负责人: DAVID E EVANS
• 金额: $ 25.03万
• 依托单位: H. LEE MOFFITT CANCER CTR & RES INST
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7706832
• 关键词: Accounting; Acetylcholine; Affect; Alzheimer' s Disease; Area; Attention; Attention Deficit Disorder; Attentional deficit; Back; Behavioral; Brain; Cessation of life; Characteristics; Cholinergic Receptors; Cigarette; Cognition; Cognition Disorders; Cognitive; Cognitive deficits; DRD2 gene; Data Collection; Development; Disease; Dopamine; Double-Blind Method; Event; Event-Related Potentials; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Genotype; Impaired cognition; Individual; Individual Differences; Laboratories; Lead; Methodology; Molecular Genetics; Motivation; Nature; Neurocognitive; Nicotine; Nicotine Withdrawal; Nicotinic Receptors; Outcome Measure; Participant; Patient Self-Report; Performance; Personality; Pharmacotherapy; Phenotype; Process; Reaction Time; Receptor Gene; Relapse; Relative (related person); Reporting; Research; Schizophrenia; Short-Term Memory; Smoke; Smoker; Smoking; Smoking Behavior; Societies; Subgroup; Symptoms; Tobacco; Tobacco use; Variant; Withdrawal; Withholding Treatment; behavior measurement; cholinergic; cognitive control; deprivation; disorder later incidence prevention; genetic profiling; improved; indexing; men; practical application; public health relevance; receptor; relating to nervous system; sex; smoking cessation; treatment program

DESCRIPTION (provided by applicant): Smoking tobacco remains the top preventable cause of disease and death in our society. Nicotine withdrawal is a major contributor to the persistent nature of tobacco use, as well as the frequent occurrence of relapse following attempts at smoking cessation. Reduced attentional control is a well-established symptom of nicotine withdrawal. Resumption of smoking/nicotine reduces this attentional disturbance, and may even increase attentional control above baseline levels. Nicotine-induced enhancement of attention may be greater among subgroups that have cognitive-attentional deficits, such as schizophrenia and attention deficit disorder. Importantly, individuals without specific cognitive disorders may possess phenotypes that contribute to the relative degree of attentional disruption during nicotine withdrawal, thereby contributing to the motivation to use tobacco. Individual differences at the molecular genetic level may in part account for these differences. Nicotinic acetylcholine activity is associated with attentional processing, and variants on specific nicotinic acetylcholine receptor genes have been associated with smoking behavior. In addition, nicotine increases dopamine release in many brain areas, including those relevant to attentional control. Indeed, a number of dopamine-related genotypes have been associated with both smoking behavior and attention, albeit in opposing directions. We propose to examine nicotinic-related and dopaminergic genotypes as moderators of nicotine deprivation effects on behavioral and neural indices of attentional control. Two well established tasks (oddball and N-back) will be included to assess attentional control and working memory. These tasks have been studied extensively using event-related brain potential (ERP) methodology. ERP may provide a more sensitive index of cognitive-attentional differences relative to strictly behavioral measures. Eighty-six (43 men) smokers will attend two laboratory sessions following overnight smoking deprivation. In a double-blind and counterbalanced fashion, participants will smoke four nicotine-containing cigarettes throughout one session, and four denicotinized cigarettes during the other. During both sessions, participants will complete the executive attention-related tasks, including concurrent ERP data collection. We hypothesize that the deprived condition will be associated with lower attentional control and working memory, and that genotypes indicative of reduced dopaminergic and nicotinic cholinergic activity will moderate nicotine deprivation induced decrements in attentional control and working memory. We expect to utilize the information gained from this exploratory/developmental research to develop and evaluate smoking cessation and relapse prevention treatment programs. For instance, there are a number of apparently safe and non-addictive nicotine-related compounds believed to improve cognition; these may provide additional support for cessation among smokers with genotypes suggestive of greater vulnerability to withdrawal induced attentional deficits. PUBLIC HEALTH RELEVANCE: The purpose of this research is to better understand disturbances in attentional control resulting from nicotine withdrawal, including genetic moderation of these effects. This research may lead to practical applications, such as matching of individual genetic profiles and cognitive characteristics with appropriate behavioral and pharmacotherapy smoking cessation treatments.

描述（由申请人提供）：吸烟仍然是我们社会中可预防的疾病和死亡的首要原因。尼古丁戒断是烟草使用持续性的主要原因，也是尝试戒烟后经常复发的主要原因。注意力控制力下降是尼古丁戒断的一个公认症状。恢复吸烟/尼古丁可以减少这种注意力障碍，甚至可以将注意力控制提高到基线水平以上。尼古丁引起的注意力增强可能在有认知注意力缺陷的亚组中更大，如精神分裂症和注意力缺陷障碍。重要的是，没有特定认知障碍的个体可能具有有助于尼古丁戒断期间注意力中断的相对程度的表型，从而有助于使用烟草的动机。分子遗传水平上的个体差异可能部分地解释了这些差异。烟碱乙酰胆碱活性与注意力处理相关，特定烟碱乙酰胆碱受体基因的变异与吸烟行为相关。此外，尼古丁增加了许多大脑区域的多巴胺释放，包括那些与注意力控制相关的区域。事实上，许多多巴胺相关的基因型与吸烟行为和注意力都有关，尽管方向相反。我们建议研究尼古丁相关和多巴胺能基因型作为尼古丁剥夺对注意力控制的行为和神经指标影响的调节剂。将包括两个完善的任务（oddball和N-back），以评估注意力控制和工作记忆。这些任务已被广泛研究使用事件相关脑电位（ERP）的方法。相对于严格的行为测量，ERP可以提供更敏感的认知-注意差异指标。86名（43名男性）吸烟者将在整夜戒烟后参加两次实验室会议。在双盲和平衡的方式中，参与者将在一个会话期间吸烟四支含尼古丁的香烟，在另一个会话期间吸烟四支脱尼古丁香烟。在这两次会议期间，参与者将完成与管理注意力相关的任务，包括同时收集ERP数据。我们推测，剥夺条件将与较低的注意力控制和工作记忆，基因型指示减少多巴胺和烟碱胆碱能活性将中度尼古丁剥夺引起的注意力控制和工作记忆的下降。我们希望利用从这项探索性/发展性研究中获得的信息来开发和评估戒烟和预防复发的治疗方案。例如，有一些明显安全和非成瘾性的尼古丁相关化合物被认为可以改善认知;这些可能为戒烟者提供额外的支持，这些吸烟者的基因型表明更容易受到戒断引起的注意力缺陷的影响。公共卫生相关性：本研究的目的是更好地了解尼古丁戒断引起的注意力控制障碍，包括这些影响的遗传调节。这项研究可能会导致实际应用，例如将个体遗传特征和认知特征与适当的行为和药物治疗戒烟治疗相匹配。