Neuroimaging of Nicotine Dependence, Depression and Emotion Regulation

描述(申请人提供)：吸烟和情感功能是紧密交织在一起的，大量研究表明，失调的情感是维持吸烟和重新吸烟的主要因素。吸烟者经常将戒烟引起的负面影响(NA)作为重新开始吸烟(即戒烟)的主要因素。这一点意义重大 鉴于这一点，失误是全面复发的最佳预测指标之一。患有严重抑郁障碍(MDD)的吸烟者吸烟率明显更高，在戒烟期间报告的NA更大，与非抑郁症(ND)个人相比，复发的风险更大。尽管人们已经做了大量的工作来描述MDD和ND个体中情绪失调与吸烟之间的联系，但很少有人关注这种联系的神经基础，而且据我们所知，还没有报道关注吸烟和抑郁对调节情感过程的能力(即情绪调节[ER])的影响。最近，我们已经证明，戒烟通过影响额叶执行功能来扰乱情绪功能。此外，这种调节在抑郁症状加重的吸烟者中似乎更明显。虽然这些数据为戒烟对情绪反应的作用提供了新的见解，但它们未能揭示吸烟和抑郁共病的神经基础，以及它们对情绪主动调节的交互作用。确定吸烟-抑郁对内质网的影响对于理解成瘾和精神疾病背景下的自我调节失败至关重要。此外，尽管NA增加会导致吸烟复发，但ER和吸烟复发之间的关联仍不清楚。因此，这一应用程序的目标是使用情感神经科学来研究吸烟的影响 内质网抑郁及其与吸烟行为的相互作用。我们的主要假设是，戒烟会通过影响额叶执行功能来扰乱ER，而抑郁症会使这种影响变得更糟。此外，我们假设ER失败将与实验室中模拟的吸烟疏忽行为有关。患有和不患有MDD的依赖型吸烟者(n=60)将在急诊室任务期间进行两次扫描：照常吸烟和24小时戒烟。患有和不患有MDD的非吸烟者对照组也将接受两次扫描。在另一次访问中，NS和ABS吸烟者将获得金钱补贴，以执行急诊室任务，而对于吸烟者，将抵制随意吸烟的机会。这项拟议的研究意义重大，因为它将为控制抑郁症和吸烟之间联系的神经机制提供新的线索。尽管这些因素之间的关联已知且代价高昂，但人们对它们的共同出现知之甚少，这些信息将为开发新的和更有效的干预措施提供基础。例如，对我们假设的支持将指导使用神经刺激(RTMS)、行为(CBT)和/或药理学技术对吸烟者进行干扰情绪信息处理的有针对性干预的基本原理。

DESCRIPTION (provided by applicant): Smoking and affective function are closely intertwined and considerable research suggests that dysregulated affect is a primary factor in the maintenance of, and relapse to smoking. Smokers frequently cite withdrawal-induced negative affect (NA) as a primary factor for re-initiating smoking (i.e. smoking lapse). This is significant given that lapses are one of the best predictors of full-blown relapse. Smokers with major depressive disorder (MDD) smoke at significantly higher rates, report greater NA during abstinence and are at greater risk for relapse than non-depressed (ND) individuals. Although considerable work has been conducted to characterize the association between dysregulated affect and smoking among MDD and ND individuals, little work has focused on the neural bases of this association, and to our knowledge, no reported work has focused on the effects of smoking and depression on the ability to regulate affective processes (i.e. emotion regulation [ER]). Recently, we have demonstrated that smoking abstinence disrupts emotional function via its impact on frontal executive function. Moreover, this modulation appears to be greater among smokers with elevated depressive symptoms. Whereas those data provide novel insights into the role of withdrawal on emotional reactivity, they fail to inform the neural basis of smoking-depression comorbidity and their interactive effects on the proactive regulation of emotion. Identifying smoking-depression effects on ER is critical for understanding self-regulation failure in the context of addiction and mental illness. In addition, though increased NA precipitates smoking relapse, associations between ER and smoking relapse remain unknown. Therefore, the goal of this application is to use affective neuroscience to investigate the effects of smoking and depression on ER, and their interaction with smoking behavior. Our overarching hypothesis is that smoking abstinence will disrupt ER via its impact on frontal executive function and that depression will worsen the effects. Furthermore, we hypothesize that ER failure will be associated with smoking lapse behavior as modeled in the laboratory. Dependent smokers (n=60) with and without MDD will be scanned during an ER task on two occasions: smoking as usual, and 24hrs abstinent. A nonsmoker control group with and without MDD will also be scanned on two occasions. On a separate visit, NS and ABS smokers will receive a monetary reinforcement to perform the ER task, and for smokers, resist the opportunity to smoke ad lib. The proposed research is significant as it will shed new light on the neural mechanisms that govern associations between depression and smoking. Despite known and costly associations between these factors, little is known regarding their co-occurrence and such information will provide a foundation for the development of novel and more effective interventions. For instance, support for our hypotheses will guide the rationale development of targeted interventions for disrupted emotional information processing in smokers using neural stimulation (rTMS), behavioral (CBT) and/or pharmacologic techniques.