Anterior insula activation during inhibition to smoking cues is associated with ability to maintain tobacco abstinence.
ABSTRACT: Relapse to smoking after initial abstinence is a major clinical challenge with significant public health consequences. At the brain and behavioral level, those who relapse to tobacco smoking have both greater cue-reactivity and lower inhibitory control than those who remain abstinent. Little is known about neural activation during inhibitory control tasks in the presence of drug-related cues. In the current study, tobacco smokers (SMK; n?=?22) and non-smoking controls (CON; n?=?19) completed a Go/NoGo task involving smoking cues during a functional magnetic resonance imaging (fMRI) scan. Following the scan session, smokers were required to quit smoking, and maintenance of abstinence was evaluated as part of a 12-week smoking cessation trial. We evaluated pre-cessation brain activity during NoGo trials in smokers who were versus were not able to quit smoking. We then compared fMRI and inhibitory control measures between smokers and non-smokers. We did not find differences between SMK and CON in performance or activation to smoking or neutral cues. However, compared to SMK who relapsed, SMK who attained biochemically-validated abstinence at the end of the smoking cessation trial had greater neural activation in the anterior insula during NoGo trials specifically with smoking-related cues. Results indicate that within SMK, decreased inhibitory control activation during direct exposure to drug-related stimuli may be a marker of difficulty quitting and relapse vulnerability.
Project description:The reasons that some smokers find it harder to quit than others are unclear. Understanding how individual differences predict smoking cessation outcomes may allow the development of more successful personalized treatments for nicotine dependence. Theoretical models suggest that drug users might be characterized by increased sensitivity to drug cues and by reduced sensitivity to nondrug-related natural rewards. We hypothesized that baseline differences in brain sensitivity to natural rewards and cigarette-related cues would predict the outcome of a smoking cessation attempt.Using functional magnetic resonance imaging, we recorded prequit brain responses to neutral, emotional (pleasant and unpleasant), and cigarette-related cues from 55 smokers interested in quitting. We then assessed smoking abstinence, mood, and nicotine withdrawal symptoms during the course of a smoking cessation attempt.Using cluster analysis, we identified 2 groups of smokers who differed in their baseline responses to pleasant cues and cigarette-related cues in the posterior visual association areas, the dorsal striatum, and the medial and dorsolateral prefrontal cortex. Smokers who showed lower prequit levels of brain reactivity to pleasant stimuli than to cigarette-related cues were less likely to be abstinent 6 months after their quit attempt, and they had higher levels of negative affect during the course of the quit attempt.Smokers with blunted brain responses to pleasant stimuli, relative to cigarette-related stimuli, had more difficulty quitting smoking. For these individuals, the lack of alternative forms of reinforcement when nicotine deprived might be an important factor underlying relapse. Normalizing these pathological neuroadaptations may help them achieve abstinence.
Project description:Lung screening is an opportunity for smoking cessation and relapse prevention, but smoking behaviors may differ across screening results. Changes in smoking were evaluated among 18 840 current and former smokers aged 55-74 scheduled to receive three annual lung screenings.Participants were randomized to low-dose computed tomography or single-view chest radiography in the American College of Radiology/National Lung Screening Trial. Outcome measures included point and sustained (6-month) abstinence and motivation to quit among smokers; and relapse among smokers who quit during follow-up, recent quitters (quit < 6 months), and long-term former smokers (quit ? 6 months).During five years of follow-up, annual point prevalence quit rates ranged from 11.6%-13.4%; 48% of current smokers reported a quit attempt and 7% of long-term former smokers relapsed. Any false positive screening result was associated with subsequent increased point (multivariable hazard ratio HR = 1.23, 95% CI = 1.13, 1.35) and sustained (HR = 1.28, 95% CI = 1.15, 1.43) abstinence among smokers. Recent quitters with ?1 false positive screen were less likely to relapse (HR = 0.72, 95% CI = 0.54, 0.96). Screening result was not associated with relapse among long-term former smokers or among baseline smokers who quit during follow-up.A false positive screen was associated with increased smoking cessation and less relapse among recent quitters. Consistently negative screens were not associated with greater relapse among long-term former smokers. Given the Affordable Care Act requires most health plans to cover smoking cessation and lung screening, the impact and cost-effectiveness of lung screening could be further enhanced with the addition of smoking cessation interventions.
Project description:Smokers with posttraumatic stress disorder (PTSD) have increased difficulty achieving and maintaining abstinence. Contingency management approaches to smoking cessation interventions have demonstrated short-term efficacy but are limited by high rates of relapse. The goal of this pilot study was to evaluate the usability and feasibility of a smartphone-based smoking cessation application (Stay Quit Coach) designed to prevent relapse among individuals with PTSD.Smokers (N = 11) were randomized to (1) QUIT4EVER, an intervention combining mobile contingency management smoking cessation counseling and medications, and Stay Quit Coach or (2) a contact control condition that was identical to QUIT4EVER except Stay Quit Coach was not included. The primary outcome was prolonged smoking abstinence.Among those queried during the follow-up periods, average Stay Quit Coach helpfulness ratings were high and ranged from 7.25 to 10 on a 10-point Likert scale (with higher scores corresponding to greater helpfulness). The Stay Quit Coach was rated by participants as being most effective at helping to quit smoking, helping to remain quit, and providing support and relevant information about quitting. Among the three quitters in the QUIT4EVER group, all reported abstinence at 3 and 6 months; however, abstinence was only bioverified for one quitter at 6 months. Among the four quitters in the contact control condition group, three reported abstinence at 3 and 6 months, but abstinence was not confirmed by bioverification.Smokers with PTSD express interest in and helpfulness of Stay Quit Coach for remaining abstinent after a quit attempt. Combined use of mobile contingency management and Stay Quit Coach is a feasible and acceptable adjunctive smoking cessation treatment for reducing smoking among smokers with PTSD. Adequately powered clinical trials are needed to demonstrate the long-term efficacy of this combined approach to smoking cessation. This study [Use of Technological Advances to Prevent Smoking Relapse among Smokers with PTSD (QUIT4EVER)] was registered on www.clinicaltrials.gov . clinicaltrials.gov identifier: NCT01990079.
Project description:<h4>Rationale</h4>Given that most attempts to quit smoking fail, it is critical to increase knowledge about the mechanisms involved in smoking relapse and resumption (i.e., the increase in smoking over time after a quit attempt). Neurocognitive measures, such as event-related potentials (ERPs), may provide novel insights into smoking relapse and resumption.<h4>Objectives</h4>The objective of the present study is to investigate the association between smoking relapse and resumption and ERPs reflecting smoking cue reactivity (i.e., P300, LPP), inhibitory control (i.e., N2, P3), and error processing (i.e., error-related negativity (ERN), Pe).<h4>Methods</h4>Seventy-two smokers viewed smoking and neutral pictures and performed a Go-NoGo and an Eriksen Flanker task, while ERPs were measured using electroencephalography. All smokers started a quit attempt in the week following the laboratory visit. Smoking behavior after the quit attempt was measured at 4, 8, and 12 weeks. Both relapse (i.e., 7-day point prevalence at 12 weeks) and smoking resumption (i.e., the number of cigarettes a day at 4, 8, and 12 weeks) were used as outcome measures.<h4>Results</h4>Logistic regression analyses showed that smaller P3 amplitudes, reflecting brain activation associated with inhibitory control, are related to an increased relapse risk. Latent growth curve analyses showed that reduced post-error slowing, the main behavioral measure reflecting error processing, is associated with stronger smoking resumption. ERPs reflecting smoking cue reactivity were unrelated to smoking relapse or resumption.<h4>Conclusions</h4>The finding that smaller inhibitory control-related P3 amplitudes are associated with increased relapse risks suggests that strategies to increase inhibitory control in smokers are worth further investigation in the search for more effective smoking cessation interventions.
Project description:A potential new treatment in smoking cessation and relapse prevention is nicotine vaccination which is based on active immunization against the nicotine molecule. This immunization will elicit the immune system to produce nicotine-specific antibodies that sequester nicotine in the blood stream, after inhaling tobacco products. The resulting antibody-antigen is too large to cross the blood-brain barrier and is therefore postulated to attenuate the rewarding effect of nicotine by preventing the latter from reaching its receptors in the brain and causing the release of dopamine. The aim of this paper is to describe the design of a phase IIb, multi-center, double blind, randomized, placebo controlled trial to assess the efficacy of the nicotine vaccine NicVAX® co-administered with varenicline (Champix®) and intensive counseling as an aid in smoking cessation and relapse prevention.Two centers will include a total of 600 smokers who are motivated to quit smoking. At week -2 these smokers will be randomized, in a 1:1 ratio, to either 6 injections of NicVAX® or placebo, both co-administered with 12-weeks of varenicline treatment, starting at week 0. The target quit day will be set after 7 days of varenicline treatment at week 1. Smokers will be followed up for 54 weeks. The primary outcome is defined as biochemically validated prolonged smoking abstinence from week 9 to 52. Secondary outcomes include safety, immunogenicity, smoking abstinence from week 37 to 52, abstinence from week 9 to 24, abstinence in the subset of subjects with the highest antibody response, and lapse/relapse rate.This is the first study to assess the efficacy of a nicotine conjugate vaccine in combination with an evidence-based smoking cessation pharmacotherapy (varenicline) to quit smoking. Although NicVAX® is primarily designed as an aid to smoking cessation, our study is designed to explore its potential to maintain abstinence and prevent relapse. The results of this trial will give a unique insight in the potential of nicotine vaccination for relapse prevention.ClinicalTrials.gov: (NCT00995033).
Project description:OBJECTIVE:Most smokers want to quit but most cessation attempts end in failure. Alcohol consumption is associated with smoking behavior and relapse. We examined the associations between severity of drinking and psychological processes during a cessation attempt in the laboratory and during a quit attempt. METHODS:Smokers (N=209) enrolled in a smoking cessation study were followed from 2 weeks pre-quit through 4 weeks post-quit. Participants scoring 0-7 and 8-15 on the Alcohol Use Disorders Identification Test (AUDIT) were classified as low-risk and high-risk drinkers, respectively. Participants attended one pre-quit laboratory session before which they were required to abstain from smoking and another pre-quit session before which they smoked normally. Craving was assessed in the laboratory with the Questionnaire for Smoking Urges (QSU). A subsample of the participants also completed a 1-week ecological momentary assessment (EMA) study starting on the quit day. During EMA, craving for cigarettes was assessed, and attentional bias was assessed using a smoking Stroop task (n=119). RESULTS:High (vs. low) risk participants reported greater abstinence-induced increases in craving in the laboratory, and also exhibited greater attentional bias on the smoking Stroop task during EMA. CONCLUSIONS:High-risk drinkers exhibited a stronger increase in desire to smoke in abstinence and greater attentional bias to smoking cues early in a quit attempt, both of which may motivate continued smoking behaviors. High-risk drinkers may require more intensive or different smoking cessation interventions.
Project description:INTRODUCTION:Thirdhand smoke (THS) residue lingers for months in homes of former smokers and may play a role in relapse after smoking cessation. This study examined the association between THS pollution as measured by the level of nicotine in house dust and continued abstinence from smoking. METHODS:Participants were 65 cigarette smokers who reported they were enrolled in any type of smoking cessation program, had set a specific date to quit, and had biochemical verification of continuous abstinence at 1-week (W1), 1-month (M1), 3-months (M3), or 6-months (M6) after their quit date. House dust samples collected at baseline before quitting were analyzed for nicotine concentration (?g/g) and nicotine loading (?g/m2) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS:Controlling for age, gender, overall and indoor smoking rates, and years lived in their home, dust nicotine concentration and loading predicted abstinence at W1, M1, M3, and M6. A 10-fold increase in dust nicotine loading and concentration were associated with approximately 50% lower odds of remaining abstinent. CONCLUSIONS:Findings suggest nicotine in house dust may play a role in facilitating relapse after smoking cessation. Additional research is warranted to investigate the causal role of THS residue in homes of former smokers on cravings and continued abstinence.
Project description:INTRODUCTION:The ability to direct smoking cessation treatment based on neuroscientific findings holds incredible promise. However, there is a strong need for consistency across studies to confirm neurobiological targets. While our prior work implicated enhanced insula reactivity to smoking cues in tobacco smoking relapse vulnerability, this finding has not been confirmed. METHOD:Using functional magnetic resonance imaging (fMRI), we evaluated the pre-cessation brain reactivity to smoking vs. neutral cues in nicotine dependent smokers who were and were not able to maintain subsequent abstinence. RESULTS:Of the 23 (7 women) individuals assessed, 13 relapsed and there were no demographic differences between those who did and did not relapse. However, smokers who relapsed showed enhanced reactivity to smoking cues in the right insula and dorsal striatum, showing significant overlap between our current and prior work despite methodological differences, including the fact that our previous work only included women. CONCLUSION:The current work supports our prior results and builds on the concept that the insula and dorsal striatum work in concert to maintain nicotine dependence. Specifically, dorsal striatal-mediated habitual responding may be triggered both by the external drug-associated cues, and the insula-mediated internal states that provide additional context motivating drug use. This replicated finding also mirrors preclinical work that finds the same individualized distinction, as only some rodents attribute incentive salience to drug cues and are more likely to reinstate drug seeking after extinction. To effectively treat addiction, these individual characteristics and their underlying neurobiological foundations must be considered.
Project description:<h4>Introduction</h4>Black cigarette smokers have lower rates of smoking cessation compared with Whites. However, the mechanisms underlying these differences are not clear. Many Blacks live in communities saturated by tobacco advertisements. These cue-rich environments may undermine cessation attempts by provoking smoking. Moreover, attentional bias to smoking cues (attention capture by smoking cues) has been linked to lower cessation outcomes. Cessation attempts among Blacks may be compromised by attentional bias to smoking cues and a cue-rich environment.<h4>Method</h4>Attention to smoking cues in Black and White smokers was examined in 2 studies. In both studies, assessments were completed during 2 laboratory visits: a nonabstinent session and an abstinent session. In study 1, nontreatment-seeking smokers (99 Whites, 104 Blacks) completed the Subjective Attentional Bias Questionnaire (SABQ; a self-report measure of attention to cues) and the Smoking Stroop task (a reaction time measure of attentional bias to smoking cues). In study 2, 110 White and 74 Black treatment-seeking smokers completed these assessments and attempted to quit.<h4>Results</h4>In study 1, Blacks reported higher ratings than Whites on the SABQ (p = .005). In study 2, Blacks also reported higher ratings than Whites on the SABQ (p = .003). In study 2, Blacks had lower biochemical-verified point prevalence abstinence than Whites, and the between-race difference in outcome was partially mediated by SABQ ratings.<h4>Conclusion</h4>Blacks reported greater attention to smoking cues than Whites, possibly due to between-race differences in environments. Greater attention to smoking cues may undermine cessation attempts.
Project description:RATIONALE:We examined the hypothesis that stress-related blunting of cortisol in smokers is particularly pronounced in those with a history of severe life adversity. OBJECTIVES:The two aims of this study were first to examine hormonal, craving, and withdrawal symptoms during ad libitum smoking and after the first 24 h of abstinence in smokers who experienced high or low levels of adversity. Second, we sought to examine the relationship between adversity and hypothalamic-pituitary-adrenal (HPA) hormones to predict relapse during the first month of a smoking cessation attempt. METHODS:Hormonal and self-report measures were collected from 103 smokers (49 women) during ad libitum smoking and after the first 24 h of abstinence. HPA hormones were measured during baseline rest and in response to acute stress in both conditions. All smokers were interested in smoking cessation, and we prospectively used stress response measures to predict relapse during the first 4 weeks of the smoking cessation attempt. RESULTS:The results showed that high adversity was associated with higher distress and smoking withdrawal symptoms. High level of early life adversity was associated with elevated HPA activity, which was found in both salivary and plasma cortisol. Enhanced adrenocorticotropic hormone (ACTH) stress response was evident in high-adversity but not in low-adversity relapsers. CONCLUSIONS:This study demonstrated that early life adversity is associated with stress-related HPA responses. The study also demonstrated that, among smokers who experienced a high level of life adversity, heightened ACTH and cortisol responses were linked with increased risk for smoking relapse.