Behavioral Genetics of Mood-Induced Smoking

情绪诱发吸烟的行为遗传学

• 批准号: 7761384
• 负责人: KENNETH Alan PERKINS
• 金额: $ 23.33万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-15 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7761384
• 关键词: Acoustics; Acute; Affect; Attenuated; Behavioral Genetics; Cigarette; Collaborations; DRD2 gene; DRD4 gene; Data; Data Analyses; Dopamine; Dopamine D2 Receptor; Dose; Drug abuse; Equilibrium; Exons; Future; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Goals; Individual; Individual Differences; Knowledge; Laboratory Study; Link; Measures; Methodology; Minisatellite Repeats; Moods; Nicotine; Nicotine Dependence; Opioid; Opioid Receptor; Pathway interactions; Patient Self-Report; Pharmaceutical Preparations; Phenotype; Procedures; Psychological reinforcement; Receptor Gene; Recording of previous events; Relapse; Reporting; Research; Resistance; Rewards; Risk; Sample Size; Severities; Smoke; Smoker; Smoking; Smoking Behavior; Time; Variant; behavioral pharmacology; depression; distress tolerance; dopamine D4 receptor; dopamine transporter; drug efficacy; drug reinforcement; efficacy testing; endogenous opioids; genetic analysis; genetic association; innovation; mu opioid receptors; negative mood; neurotransmission; novel; positive mood; prototype; public health relevance; response; serotonin transporter; sex; smoking relapse; stressor

DESCRIPTION (provided by applicant): "Behavioral Genetics of Mood-Induced Smoking" Controlled laboratory studies reliably show that negative mood manipulations of various kinds acutely increase smoking reinforcement. However, very few studies have identified individual differences that moderate mood-induced smoking, and only one, a recent report by us, has examined genetic associations. The primary aim of this proposal is to validate our prior, preliminary data on genetic associations with increases in smoking due to negative mood, a potentially important novel phenotype for nicotine dependence. Dependent smokers (N=200) will participate in two virtually identical lab sessions, differing only in induction of negative vs. positive mood via a validated procedure to robustly induce mood (one mood per session, sessions in counter-balanced order). They will ad lib smoke their preferred brand of cigarettes (to maximize generalizability) during mood induction each session. Differences in smoking reinforcement (latency and amount of smoking) between the negative and positive mood conditions, i.e. mood-induced smoking, will be related to the dopamine and mu opioid receptor gene variants identified in our preliminary study. These include: dopamine D4 receptor (DRD4 VNTR), dopamine D2 receptor (DRD2 C957T SNP [rs6277] and DRD2/ANKK1 TaqIA SNP [rs1800497]), the dopamine transporter (SLC6A3 VNTR), and the mu opioid receptor exon 1 SNP (OPRM1 A118G [rs1799971]). In secondary aims, we will examine genetic associations with smoking reward, affect, and related measures, as well as other individual differences in mood-induced smoking, including subject sex, depression history, distress tolerance, and severity of nicotine dependence. Our prior study and past productive collaborations between the PI and co-I demonstrate the strong feasibility of this proposal. Results of this innovative project may identify smokers potentially at greater risk for relapse due to negative mood and may guide research on mechanisms behind mood-induced smoking. Our procedures could be used to test the efficacy of medications to attenuate mood-induced smoking, thereby reducing vulnerability of some smokers to mood-related relapse. This project also could be a prototype for future research that combines rigorous behavioral pharmacology methodology and genetics to identify individual variation in drug reinforcement due to situational influences. PUBLIC HEALTH RELEVANCE: Negative mood increases smoking behavior and leads to relapse after a quit attempt. Controlled laboratory studies show that negative mood manipulations of various kinds (e.g. stressors) acutely increase smoking behavior. However, very few studies have identified individual differences in mood-induced smoking, and only one, a preliminary study by us, examined genetic associations with mood-induced smoking. This project will validate our preliminary observations, which may identify smokers particularly vulnerable (or resistant) to smoking relapse due to negative mood. Results may guide research on genetics of environmental influences on smoking behavior and other drug abuse, and perhaps guide research on the mechanisms behind mood-induced smoking.

描述（由申请人提供）：“情绪诱导的吸烟的行为遗传学”受控实验室研究可靠地表明，各种种类的负面情绪操纵急性增加了吸烟加强。但是，很少有研究发现了个体差异，使情绪引起的吸烟适度，而我们最近的一份报告已经检查了遗传关联。该提案的主要目的是验证我们先前的有关遗传关联的初步数据，这些数据与消极情绪引起的吸烟增加，这是尼古丁依赖性的潜在重要新表型。受抚养的吸烟者（n = 200）将参加两个实际上相同的实验室会议，仅通过经过验证的程序来诱导情绪诱导情绪（每次疗程一个情绪，以平衡顺序）的诱导诱导和积极情绪的差异。他们将在每次会议期间在情绪吸引过程中吸烟他们首选的香烟品牌（以最大程度地提高普遍性）。阴性和积极情绪状况之间的吸烟加强（潜伏和吸烟量）的差异，即情绪引起的吸烟，将与我们的初步研究中确定的多巴胺和MU阿片类受体基因变体有关。其中包括：多巴胺D4受体（DRD4 VNTR），多巴胺D2受体（DRD2 C957T SNP [RS6277]和DRD2/ANKK1 TAQIA SNP [RS1800497]），多巴胺转运蛋白转运蛋白（SLC6A3 VNTR）和MU OPIOOROROROROROROROROROROROROREOR EXP { [RS1799971]）。在次要目标中，我们将检查与吸烟奖励，情感和相关措施以及情绪引起的吸烟的其他个体差异，包括受试者性别，抑郁病史，遇险耐受性和尼古丁依赖的严重程度。我们先前的研究和PI与Co-I之间的富有生产力的合作证明了该提议的强大可行性。这个创新项目的结果可能会发现吸烟者可能由于情绪负面的情绪而有可能面临更大的复发风险，并可能指导人们对情绪引起的吸烟背后的机制进行研究。我们的程序可用于测试药物减轻情绪引起的吸烟的功效，从而减少一些吸烟者对情绪相关复发的脆弱性。该项目也可能是未来研究的原型，它结合了严格的行为药理学方法和遗传学，以确定由于情境影响而导致的药物强化差异。 公共卫生相关性：负面情绪会增加吸烟行为，并导致戒烟尝试后复发。对照实验室研究表明，各种（例如压力源）的负面情绪操纵急性增加了吸烟行为。但是，很少有研究发现了情绪引起的吸烟的个体差异，而我们的初步研究仅研究了与情绪诱导的吸烟的遗传关联。该项目将验证我们的初步观察结果，该观察可能会发现吸烟者特别脆弱（或抗药性）因情绪负面情绪而引起的吸烟复发。结果可以指导有关环境影响吸烟行为和其他药物滥用的遗传学的研究，也许可以指导人们对情绪引起的吸烟背后的机制的研究。