Individual differences in amygdala reactivity following nicotinic receptor stimulation in abstinent smokers.
Individual differences in amygdala reactivity following nicotinic receptor stimulation in abstinent smokers.
复制标题
戒烟者烟碱受体刺激后杏仁核反应性的个体差异。
DOI：
10.1016/j.neuroimage.2012.10.043
复制
发表时间：
2013
期刊：
影响因子：
5.7
通讯作者：
Stein,ElliotA
中科院分区：
文献类型：
--
作者：
Sutherland,MatthewT;Carroll,AllisonJ;Salmeron,BettyJo;Ross,ThomasJ;Hong,LElliot;Stein,ElliotA
杏仁核功能过度活跃可能是戒烟期间情绪失调的原因，也是药物戒烟辅助的一个神经生物学靶点。现有的药物治疗(例如，尼古丁替代疗法和varenicline)只能帮助一部分戒烟患者，因此，阐明这些药物的神经生物学影响对于加快改进干预措施至关重要。在一项采用受试者内、双盲、安慰剂对照设计的fMRI研究中，我们评估了24名戒烟者和20名非吸烟者在情绪面孔匹配范例中的任务表现和杏仁核功能。所有参与者都接受了大约17天的varenicline和安慰剂服药，并在每种情况下的不同日期进行了扫描，佩戴尼古丁透皮贴片或安慰剂贴片。在杏仁核反应性范式中，尼古丁和varenicline刺激烟碱型乙酰胆碱受体(NAChR)减少了戒烟者的反应时间(RT)，但对不吸烟者没有影响。当将所有吸烟者视为一个单一的同质组时，没有检测到药物对杏仁核反应性的影响。然而，在一项探索性分析中，我们根据nAChR刺激后表现出稳定表现增强的倾向的个体差异将参与者分成不同的亚组(稳定RT-改进剂[SI]与可变RT-改进剂[VI])。使用这种探索性的方法，药物似乎只在一个吸烟者亚组中调节杏仁核的反应性，而在两个非吸烟者亚组中都没有。具体地说，在SI吸烟者队列中，戒烟诱导的杏仁核反应性升高被nAChR刺激下调。相反，在没有给药的情况下表现出中等水平杏仁核反应性的VI吸烟者队列中，varenicline和尼古丁并没有调节杏仁核的功能。这些结果表明，药物治疗最明显地抑制了吸烟者的杏仁核功能，这些吸烟者似乎对戒烟诱导的效果敏感。这些发现为通过离散的神经生物学特征来区分吸烟者的表型提供了一步。
Hyperactive amygdala functioning may underlie emotional dysregulation during smoking abstinence and represents one neurobiological target for pharmacological cessation aids. Available pharmacotherapies (e.g., nicotine replacement and varenicline) aid only a subset of individuals with smoking cessation and therefore elucidating the neurobiological impact of these medications is critical to expedite improved interventions. In a fMRI study employing a within-subject, double-blind, placebo-controlled design, we assessed task performance and amygdala functioning during an emotional face matching paradigm following administration of nicotine and varenicline to 24 abstinent smokers and 20 nonsmokers. All participants underwent ~17days of varenicline and placebo pill administration and were scanned, on different days under each condition, wearing a transdermal nicotine or placebo patch. During the amygdala reactivity paradigm, nicotinic acetylcholine receptor (nAChR) stimulation by nicotine and varenicline decreased reaction time (RT) in abstinent smokers but not in nonsmokers. When considering all smokers as a single homogenous group, no drug-induced effects on amygdala reactivity were detected. However, in an exploratory analysis we parsed participants into subgroups according to individual differences in the propensity to demonstrate stable performance augmentation following nAChR stimulation (stable RT-improvers [SI] vs. variable RT-improvers [VI]). Using this exploratory approach, drugs appeared to modulate amygdala reactivity in only one smoker subgroup but not in either nonsmoker subgroup. Specifically, in the SI-smoker cohort abstinence-induced elevated amygdala reactivity was down-regulated by nAChR stimulation. In contrast, varenicline and nicotine did not modulate amygdala functioning in the VI-smoker cohort who displayed moderate levels of amygdala reactivity in the absence of drug administration. These results suggest that pharmacotherapies most robustly dampened amygdala functioning in smokers appearing susceptible to abstinence-induced effects. Such findings provide a step towards fractionating the smoker phenotype by discrete neurobiological characteristics.