Nicotine Insensitivity and Cue-Controlled Smoking Behavior in People with Schizophrenia

项目摘要 吸烟是美国主要的可预防的死亡原因。虽然大多数吸烟者都想戒烟， 只有3-5%的独立戒烟尝试和~25%的药物支持戒烟尝试成功一年。患者的 精神分裂症，烟草依赖的比率和严重程度大大高于一般人群， 这导致了这一人群的发病率更高，预期寿命更短。有证据表明 与尼古丁摄入相关的刺激和行为常规所施加的行为控制 尼古丁的高滥用潜力。精神分裂症的神经病理学表现为 对齐以促进线索锁定的习惯性吸烟模式。对主观的迟钝敏感 尼古丁（但不是尼古丁相关刺激）和额评价控制缺陷的影响是潜在的 调解员本提案的目的是确定吸烟是否会影响吸烟者的健康， 精神错乱是由不成比例的强烈线索控制和自动性，并测试是否无意义， 对尼古丁的主观影响的敏感性和/或认知控制缺陷可能是原因。线索控制 过度吸烟是操作作为维持吸烟行为的实际上尼古丁免费 香烟，它唤起了一套近乎完整的内、外感受线索和行为惯例， 与吸烟有关，但不会导致血液中尼古丁的急剧上升。具体来说，线索控制将是 通过在标准化条件下随意接触这些香烟8小时后的呼吸CO水平进行定量 在尼古丁替代品的存在下，以及在他们的消费下降（或缺乏）的条件 在整个会议过程中。对尼古丁主观效应的敏感性被量化为以下能力： 在标准化双盲条件下区分不同尼古丁产量的研究香烟，以及 这些香烟引起的主观状态效应的差异。认知控制被量化 从RDoC矩阵中选择的任务。这些和几个次要措施将获得超过 在45名患有精神分裂症的吸烟者（SmoSz）和45名健康对照吸烟者（Smo， Con），匹配人口统计学和吸烟变量。我们将测试线索控制和 尼古丁敏感性，以及尼古丁敏感性和认知控制对线索控制的影响。我们将 还可以量化尼古丁敏感性和认知控制在多大程度上可以在统计上解释这一组 cue control的区别这些结果将具有重要的治疗意义。例如，更大的线索 控制将表明，解决吸烟的习惯性，线索锁定的组成部分，如通过 最近在SmoCon试点的不同灭绝学习干预措施，可能对吸烟特别有益， 在SmoSz停止。通过塑造我们对精神分裂症患者烟草依赖的理解， sent项目可能会将治疗发展转向针对特定脆弱性的战略， 这一人群是受其对健康和生命的有害影响最严重的人群之一。

Project Summary Smoking is the leading preventable cause of death in the US. While the majority of smokers wants to quit, only 3-5% of unaided and ~25% of medication-supported quit attempts succeed for one year. In people with schizophrenia, rates and severity of tobacco dependence are substantially higher than in the general popu- lation, contributing to greater morbidity and lower life expectancy in this population. There is evidence that the behavioral control exerted by stimuli and behavioral routines associated with nicotine intake contributes substantially to nicotine’s high abuse potential. The neuropathology associated with schizophrenia appears aligned to facilitate a cue-locked, habitual mode of tobacco smoking. Blunted sensitivity to the subjective effects of nicotine (but not of nicotine-associated stimuli) and frontoevaluative control deficits are potential mediators. The aim of the present proposal is to determine whether tobacco smoking in people with schizo- phrenia is governed by disproportionately strong cue control and automaticity, and to test whether insensi- tivity to the subjective effects of nicotine and/or cognitive control deficits may account for this. Cue control over tobacco smoking is operationalized as the maintenance of smoking behavior by virtually nicotine-free cigarettes, which evoke a near-complete set of intero- and exteroceptive cues and behavioral routines as- sociated with smoking, but without the ensuant sharp rise in blood nicotine. Specifically, cue control will be quantified by breath CO levels after eight hours of ad libitum access to these cigarettes under standardized conditions in the presence of nicotine replacement, and by the decline (or lack thereof) in their consumption over the course of the session. Sensitivity to the subjective effects of nicotine is quantified as the ability to discriminate research cigarettes of differing nicotine yields under standardized double-blind conditions, and by the difference in subjective state effects evoked by these cigarette types. Cognitive control is quantified by tasks selected from the RDoC matrix. These and several secondary measures will be obtained over three laboratory visits in 45 smokers with schizophrenia (SmoSz) and 45 healthy control smokers (Smo- Con), matched for demographic and smoking variables. We will test for group differences in cue control and nicotine sensitivity, and for the impact of nicotine sensitivity and cognitive control on cue control. We will also quantify to what degree nicotine sensitivity and cognitive control can statistically account for the group difference in cue control. The results will have important treatment implications. For example, greater cue control would suggest that addressing habitual, cue-locked components of tobacco smoking, such as by different extinction learning interventions recently piloted in SmoCon, may be of particular benefit to smok- ing cessation in SmoSz. By shaping our understanding of tobacco dependence in schizophrenia, the pre- sent project may redirect treatment development toward strategies tailored to the specific vulnerabilities of this population, which is among the most severely affected by its detrimental impact on health and life.