Dopamine Genotypes, Experimentally-induced Craving, & Cessation in Female Smokers

项目概述：这个探索性/发展性R21申请的目的是表征和更好地理解多巴胺系统遗传多态性对吸烟女性中压力和吸烟线索诱导的香烟渴望和戒烟的影响。在多种文献的基础上，对有兴趣进行未经治疗的“突然停止”戒烟尝试的女性进行多学科前瞻性研究，将提供一个自然的视角，研究多巴胺相关基因型和实验室条件下压力和线索诱导的渴望对戒烟的潜在影响。为此，将对250名妇女进行多巴胺相关多态性基因分型，在目标戒烟日期的前一天参加实验室压力和线索暴露任务，并在6个月的随访间隔中，在8个时间点评估戒烟情况。通过仔细研究实验诱导的渴望反应和戒烟之间的关系，该研究将试图更好地描述多巴胺基因型影响的机制。这第一项研究将为更大规模的调查奠定基础，旨在确定在男性和女性样本的遗传（例如，多巴胺多态性）和心理生物学（例如，线索和压力诱导的渴望反应）特征背景下定制治疗（例如，提示暴露，压力管理，尼古丁替代）的有益效果，以期更好地理解女性试图戒烟所经历的独特挑战。相关性：吸烟是美国发病率和死亡率的唯一最可预防的原因。事实上，美国至少有30%的癌症死亡与吸烟有关，全球每年约有300万人死于吸烟。尽管吸烟有明显的负面后果，但仍有相当一部分人继续吸烟。此外，尽管大多数吸烟者对戒烟表现出强烈的兴趣，但很少有人能成功地保持戒烟，这一问题在女性中更为明显。因此，持续吸烟行为（即未能或难以保持戒烟）仍然是一个主要的公共卫生问题。了解戒烟成功的遗传和心理生物学决定因素是开发促进戒烟的新方法的关键的第一步，因此有必要降低癌症和其他与吸烟有关的慢性疾病的惊人比率。

DESCRIPTION (provided by applicant): Project Summary: The objective of this exploratory/developmental R21 application is to characterize and better understand the effects of genetic polymorphisms in the dopamine system on stress- & smoking cue- induced cigarette cravings and smoking cessation among women who smoke. Grounded in a diverse literature, the proposed multidisciplinary prospective study of women interested in making an untreated, 'cold turkey' smoking cessation attempt will provide a naturalistic look at potential effects of dopamine-related genotypes and stress- & cue-induced cravings elicited under laboratory conditions, on abstinence. To that end, 250 women will be genotyped for dopamine-related polymorphisms, participate in laboratory stress and cue-exposure tasks the day before their target quit date, and will be assessed for abstinence at 8 time points during a 6-month follow-up interval. By closely examining relations between experimentally-induced craving reactions and cessation, the study will attempt to better characterize mechanisms underlying the effects of dopamine genotypes. This first study will lay the groundwork for larger-scale investigations aimed at determining the beneficial effects of tailored treatments (e.g., cue-exposure, stress management, nicotine replacement) in the context of genetic (e.g., dopamine polymorphisms) and psychobiological (e.g., cue- and stress-induced craving reactions) characteristics in samples of both men and women, with an eye toward yielding a better undestanding of the unique challenges experienced by women trying to quit smoking. Relevance: Smoking is the single most preventable cause of morbidity and mortality in the United States. Indeed, smoking has been implicated in at least 30 percent of all cancer deaths in the U.S. and an estimated three million deaths per year worldwide. In spite of the clear negative consequences of smoking, a significant subset of the population continues to smoke. Moreover, although most smokers express a strong interest in quitting, few are successful at maintaining abstinence, a problem that is even more pronounced among women. Persistent smoking behavior (i.e., failure or difficulty in remaining abstinent) thus continues to be a major public health problem. Understanding the genetic and psychobiological determinants of smoking cessation success is a critical first step in developing novel approaches to promote cessation, so necessary to reduce the alarming rates of cancer and other smoking-related chronic diseases.