DRD4 VNTR polymorphism is associated with transient fMRI-BOLD responses to smoking cues

Rationale A dopamine receptor 4 variable number tandem repeat (DRD4 VNTR) polymorphism has been related to reactivity to smoking cues among smokers, but the effect of this genetic variation on brain responses to smoking cues has not been evaluated. Objectives The present study evaluated the relationship between carrying the DRD4 VNTR 7-repeat allele and transient functional magnetic resonance imaging (fMRI) blood-oxygen-level-dependent responses to smoking cues among adult dependent cigarette smokers. Materials and methods Smokers (n = 15) underwent fMRI scanning after 2-h abstinence. During scanning, they viewed visual smoking and control cues. A blood sample was assayed for the DRD4 VNTR polymorphism, and participants were categorized based on whether they carried one or two copies of the 7-repeat allele (DRD4 L, n = 7) or not (DRD4 S, n = 8). Results Contrasts in brain cue-reactivity (smoking minus control cues) between DRD4 groups were conducted using SPM2. Smoking cues as compared to control cues elicited transient brain responses in right superior frontal gyrus (BA 8/9/10/32), left anterior cingulate gyrus (BA 32), and right cuneus (BA 19). Exposure to smoking cues resulted in greater activation of right superior frontal gyrus (BA 10) and right insula in DRD4 L compared to DRD4 S individuals. By contrast, exposure to smoking cues among DRD4 S individuals resulted in no significant increases in activation compared to DRD4 L individuals. Conclusions These brain imaging results suggest that DRD4 VNTR polymorphism is related to transient brain responses to smoking cues in regions subserving executive and somatosensory processes.     

Urges to smoke during the first month of abstinence: relationship to relapse and predictors

The urges to smoke reported by 215 former smokers were measured 1 day, 7 days, 14 days and 30 days after they quit to examine: (a) the time course of smoking urges, (b) the relationship of urges to relapse, and (c) predictors of urges to smoke. Urges to smoke were strongest 1 day after quitting, and decreased at each subsequent measurement point. Urges were a powerful predictor of relapse. At each of the four assessment points, abstinent subjects who reported stronger urges to smoke were more likely to relapse by the next measurement point. Urges to smoke at a given day (e.g., day 1) were consistently the best predictors of the persistence of urges at the next assessment (e.g., day 7). Greater negative emotion (e.g., anxiety, sadness, anger, and confusion) and psychosocial stress also predicted stronger urges to smoke. Nicotine gum significantly reduced urges during week 1 post-cessation. Clinical implications of the findings are discussed.     

Effects of cigarette smoking and abstinence on stroop task performance

Rationale Smokers report enhanced concentration after cigarette smoking and difficulty concentrating when abstinent from smoking. These perceived effects may contribute to smoking cessation failures, and if so, clarification of their cognitive bases could inform treatment strategies. Selective attention may be important in this regard, but earlier literature presents inconsistent findings on how smoking abstinence and resumption of smoking influence this cognitive function. Objectives We aimed to compare smokers and nonsmokers on selective attention, and in smokers, to test the effects of overnight abstinence from smoking and of acute smoking on selective attention. Materials and methods Smokers and nonsmokers (n = 43) performed a Stroop test (two test days, two test blocks per day). Smokers participated after overnight abstinence and also within 1-h of ad libitum smoking. Smokers each smoked a cigarette between test blocks on each day; nonsmokers did not. Results Smokers demonstrated longer response latencies for both congruent and incongruent stimuli after overnight than brief abstinence, but no deficit specifically related to selective attention. Whereas nonsmokers showed no changes in performance in the second test block, smoking between blocks reduced the Stroop effect when smokers were abstinent overnight. Conclusions These data are consistent with the hypothesis that abstinence from smoking among nicotine-dependent individuals has deleterious effects on cognitive performance, but do not indicate that selective attention is adversely effected. Improvement in selective attention after terminating abstinence with one cigarette may also contribute to smokers’ perceived enhanced ability to concentrate after smoking.     

Selective attention to smoking cues in former smokers

Repeated drug use modifies the emotional and cognitive processing of drug-associated cues. These changes are supposed to persist even after prolonged abstinence. Several studies demonstrated that smoking cues selectively attract the attention of smokers, but empirical evidence for such an attentional bias among successful quitters is inconclusive. Here, we investigated whether attentional biases persist after smoking cessation. Thirty-eight former smokers, 34 current smokers, and 29 non-smokers participated in a single experimental session. We used three measures of attentional bias for smoking stimuli: A visual probe task with short (500 ms) and long (2000 ms) picture stimulus durations, and a modified Stroop task with smoking-related and neutral words. Former smokers and current smokers, as compared to non-smokers, showed an attentional bias in visual orienting to smoking pictures in the 500 ms condition of the visual probe task. The Stroop interference index of smoking words was negatively related to nicotine dependence in current smokers. Former smokers and mildly dependent smokers, as compared to non-smokers, showed increased interference by smoking words in the Stroop task. Neither current nor former smokers showed an attentional bias in maintained attention (2000 ms visual probe task). In conclusion, even after prolonged abstinence smoking cues retain incentive salience in former smokers, who differed from non-smokers on two attentional bias indices. Attentional biases in former smokers operate mainly in early involuntary rather than in controlled processing, and may represent a vulnerability factor for relapse. Therefore, smoking cessation programs should strengthen self-control abilities to prevent relapses.     

Relapse to smoking after 1 year of abstinence: a meta-analysis

Most clinical trials use 6 months or 1 year follow-ups as proxies for life-time smoking cessation. Retrospective studies have estimated 2–15% of smokers relapse each year after the first year of abstinence, but these have methodological problems such as memory bias. We searched for prospective studies of adult quitters that reported the number of participants abstinent at 1 yr follow-up and who remained abstinent at ≥ 2 year follow-ups. We included studies that reported the percent which remained lapse-free, did not continue treatment after 1 year, and had ≤ 10% lost-to-follow-up. We did not locate any population-based studies but did locate eight randomized, controlled trials, all testing nicotine medications. After deleting one trial with outlier results, a meta-analysis estimated the annual incidence of relapse after 1 year to be 10%; however, the small sample sizes resulted in a wide 95% confidence interval (5–17%) suggesting this estimate is not very accurate. We conclude a non-significant amount of relapse occurs after 1 year. Better quantification of this relapse rate is important to improve estimates of life-long abstinence and reductions in morbidity and mortality from smoking cessation.     

Acute psychomotor,subjective and physiological responses to smoking in depressed outpatient smokers and matched controls

Rationale Cigarette smoking is highly prevalent in people diagnosed with depression, and depressed smokers are less likely to quit. Examining depressed smokers’ responses to smoking will help determine the role of depression in maintaining cigarette smoking. Objectives To determine the psychomotor, subjective and physiological effects of cigarette smoking in currently depressed smokers versus matched controls. Materials and methods Fourteen currently depressed smokers and 14 never-depressed smokers, matched in age, gender, nicotine dependence and daily cigarette consumption, smoked three cigarettes at half-hourly intervals. All smokers were non-deprived. Self-reported mood and craving for cigarettes, performance on a simple reaction time task, expired-air carbon monoxide, heart rate and blood pressure were assessed before and after smoking each cigarette. Smoking topography was also assessed. Results Depressives and controls did not differ in terms of dependence on cigarettes or expired-air carbon monoxide. Topographic and cardiovascular measures were similar in depressed and control participants, suggesting that they smoke cigarettes in a similar manner. However, depressives displayed enhanced reaction time performance after the first cigarette. Positively reinforced craving was reduced after smoking each cigarette but returned to baseline levels within 30 min in depressed but not in control smokers. Depressed smokers also displayed higher levels of negatively reinforced craving. Both depressives and controls reported improved positive mood after smoking. Conclusions Cigarette smoking in non-deprived depressed smokers enhances psychomotor performance and the reduction of positively reinforced craving in depressed smokers after smoking is transient, suggesting that enhanced craving may play a role in the maintenance of smoking in depression.     

Exposure to smoking cues: cardiovascular and autonomic effects

Laboratory exposures to smoking cues have been shown to reliably induce self-reported cigarette cravings among smokers, a model of environmentally triggered urges to smoke that can contribute to poorer cessation success. Several studies have also demonstrated that cue exposures give rise to changes in heart rate and blood pressure. Few studies, however, have investigated possible cue effects on heart rate and blood pressure variability (HRV and BPV). Particularly intriguing in this regard are cardiac oscillations in the low (i.e., 0.04-0.15 Hz), and high (i.e., 0.15-0.50 Hz) frequency range, which are thought to reflect components of autonomic control and response to environmental challenges. A closer examination of cardiovascular reactivity may thus help characterize the autonomic response to smoking cue exposure. To that end, an experimental study was conducted in which nicotine dependent daily smokers (n=98) were exposed to guided imagery of neutral and smoking situations, while continuous, noninvasive, beat-to-beat cardiovascular data were collected. Consistent with previous research, the findings revealed significant increases in both systolic and diastolic blood pressure during smoking imagery, relative to neutral imagery. In addition, power spectral density analyses of heart rate and blood pressure variability revealed elevated HRV and BPV in both the low- and high-frequency ranges during the smoking imagery. The results suggest the presence of an autonomic component to smoking cue reactivity, and also raise the possibility of long-term negative cardiac consequences for smokers who ubiquitously encounter cues in their daily environments.     

Impulsivity-like traits and smoking behavior in college students

Recent research has deconstructed the concept of impulsivity by identifying five different traits that influence engagement in impulsive behaviors: positive urgency (tendency to act rashly in response to a positive mood), negative urgency (tendency to act rashly in response to a negative mood), sensation seeking, lack of planning, and lack of perseverance. The traits are only moderately related to each other. The aim of this study was to apply this advance to the study of smoking. We tested a two-stage hypothesis: Higher sensation seeking was hypothesized to differentiate current smokers from non-smokers, and negative and positive urgencies were expected to predict concurrent level of nicotine dependence among smokers. As anticipated, greater sensation seeking was associated with a higher odds of being a current smoker (odds ratio = 1.51). Greater positive urgency, but not other impulsivity-related traits, was associated with significantly higher levels of nicotine dependence, explaining 29% of the variance in level of nicotine dependence.     

Craving effect of smoking cues in smoking and antismoking stimuli in light smokers

Cue-reactivity models may be able to inform light and intermittent smoking patterns not yet explained by withdrawal models. For instance, smoking cues in smoking and antismoking advertisements may elicit cravings in smokers at equal rates, which may promote smoking maintenance. Moreover, smoking has been associated with impulsivity, but has not been explored in light and intermittent smokers (LITS). Aims of this study included the assessment of the impact of smoking and antismoking advertisements on post-exposure cravings in LITS and assessment of impulsivity as a moderator between cue exposure and cravings. Data from 155 LITS were analyzed. Participants were exposed to one of three stimuli conditions (i.e., smoking, antismoking, and neutral) and completed measures of demographics, tobacco use and history, impulsivity, and cravings. Univariate analysis demonstrated that smoking stimuli produced higher cravings relative to antismoking and neutral stimuli, whereas no differences between antismoking and neutral stimuli were observed. Impulsivity did not moderate the relationship between stimuli condition and cravings. Implications stemming from these findings include the further regulation of smoking advertisements and future exploration of smoking and smoking cessation in the context of cue-reactivity.     

Effects of smoking abstinence on adult smokers with and without attention deficit hyperactivity disorder: results of a preliminary study

Rationale Individuals with attention deficit hyperactivity disorder (ADHD) smoke at higher rates than the general population; however, little is known about the mechanisms underlying this comorbidity. Objective This study evaluated the effects of overnight abstinence on withdrawal symptoms and cognitive performance in adult smokers with and without ADHD. Materials and methods Individuals smoking ≥15 cigarettes per day were recruited from the community and underwent an evaluation to establish a diagnosis of ADHD (n = 12) or not (n = 14). Withdrawal symptoms, mood, craving, cognitive performance, and smoking cue reactivity were measured during two laboratory sessions—in a ‘Satiated’ condition participants smoked up to and during the session while in an ‘Abstinent’ condition, participants were required to be smoking abstinent overnight and remain abstinent during the session. Results The effects of abstinence on ADHD and non-ADHD smokers did not differ for withdrawal symptom severity, mood, craving or cue reactivity. Significant Group × Condition interactions were observed for measures of attention and response inhibition on the Conners’ CPT. For reaction time (RT) variability and errors of commission, the ADHD group exhibited greater decrements in performance after overnight abstinence compared to the non-ADHD group. The effects of abstinence on other cognitive measures (e.g., rapid visual information processing task, cued Go/No-Go task) did not differ between the two groups. Conclusion This preliminary study is the first to systematically evaluate the effects of acute smoking abstinence in adult smokers diagnosed with ADHD. Individuals with the disorder may smoke at higher rates due to greater worsening of attention and response inhibition after abstinence.     

Using mobile eye-tracking to assess attention to smoking cues in a naturalized environment

Introduction

Attentional bias to drug cues is thought to contribute to maintenance of drug-use behavior among chronic drug users. Studies assessing this bias traditionally have assessed drug cues that are explicitly presented in a laboratory setting. This study tested the use of a mobile eye-tracking procedure to assess visual attention to smoking cues by smokers and non-smokers in a more naturalized environment.

Methods

A mobile eye-tracker was used to assess the number and duration of fixations made to smoking cues located in an office space environment by smokers and non-smokers while completing a sham experimental task. Smokers completed two sessions, once after 12 h of abstinence and once after smoking.

Results

Results indicated that smokers made significantly more fixations to the smoking cues than non-smokers, regardless of smoking condition though the mean amount of time spent fixating on the cues did not differ significantly. Smokers did not differ in the number of fixations or mean fixation duration across the two smoking conditions, suggesting in this sample that a 12-h period of abstinence did not make the smoking cues more salient in this context.

Conclusion

This study demonstrates the successful use of mobile eye-tracking to assess attentional biases to environmental drug cues. Results suggest that smoking cues in the environment are potentially more attention grabbing for smokers compared to non-smokers but these cues do not necessarily hold visual attention of smokers longer than that of non-smokers.     

Attentional and approach biases for smoking cues in smokers: an investigation of competing theoretical views of addiction

Rationale Different theories of addiction make conflicting predictions about whether attentional and approach biases for smoking-related cues are enhanced, or reduced, as a function of the level of nicotine dependence.Objective These theoretical views were evaluated by examining cognitive biases in smokers.Methods We monitored the eye movements of 41 smokers (predominantly young adults, who smoked from one to 40 cigarettes per day) as they completed a visual probe task in which smoking-related and matched control pictures were presented. Participants also completed a stimulus-response compatibility task, which measured the tendency to approach smoking-related cues, and a rating task.Results Smokers with lower levels of nicotine dependence showed greater maintained attention and faster approach responses to smoking-related cues. Longer gaze times for smoking cues were associated not only with lower levels of nicotine dependence, but also with higher levels of craving.Conclusions Overall, the results seem consistent with an integrated incentive-habit model of addiction.     

Increases in impulsivity following smoking abstinence are related to baseline nicotine intake and boredom susceptibility

Trait impulsivity and response inhibition have been shown to be related to smoking behavior. One measure of response inhibition - antisaccade performance, or the ability to inhibit looking at a novel stimulus - has been shown to be worsened by smoking abstinence, improved by nicotine administration and predictive of smoking cessation outcomes. However, relations between antisaccade performance and measures of trait impulsivity have not been extensively evaluated in smokers. In the present study, twelve dependent smokers (n=12) completed an eye tracking task following smoking as usual and overnight abstinence; and they completed baseline measures of trait impulsivity, smoking history and provided biological samples. As expected, overnight abstinence significantly increased antisaccade errors (p<0.002) while having no effect on prosaccade performance. Abstinence-induced increases in antisaccade errors were positively correlated with baseline plasma cotinine and Sensation Seeking Scale Boredom Susceptibility, and negatively correlated with IQ. These results suggest that smoking abstinence significantly increases errors of response inhibition and that the magnitude of this increase is related to trait impulsivity and nicotine intake variables.     

Alcohol increases cognitive biases for smoking cues in smokers

Rationale Alcohol increases the motivation to smoke, possibly because it increases the incentive motivational properties of smoking cues.Objectives We examined whether alcohol would increase attentional, approach, and evaluative biases for smoking-related cues in a sample of daily cigarette smokers.Methods The study used a visual probe task with eye movement recording to investigate biases in visual orienting to smoking-related cues. A stimulus–response compatibility task was used to assess approach tendencies for smoking-related cues, and an explicit rating task was used to assess the perceived valence of smoking-related cues. Participants completed the tasks in two sessions, once after consumption of 0.4 g/kg alcohol and once after consumption of a non-alcoholic drink.Results Alcohol increased the maintenance of attention on smoking cues (evident from gaze duration and a reaction time index of attentional bias), the perceived pleasantness of smoking cues, and cigarette craving, relative to the non-alcoholic drink. However, alcohol had no effect on the initial shifting of gaze to smoking cues or on the tendency to approach smoking cues.Conclusions These results suggest that, in smokers, ingestion of a moderate dose of alcohol increases the propensity for smoking-related cues to hold attention and makes those cues seem more attractive, which is consistent with alcohol increasing the incentive salience of smoking cues.     

Attentional avoidance of smoking cues in former smokers

It has been speculated that attentional bias (AB) to smoking cues is a permanent feature of addiction. The objective of the present study was to investigate if abstinence duration has an influence on AB. Performance on a visual probe task of three groups (recent, intermediate and prolonged) of ex-smokers (n = 62, mean age 50 ± 11 years) with different abstinence durations was compared. Target/Control images were presented at three stimulus onset asynchronies (SOAs: 200, 500, and 2000 ms) on a 17-inch monitor. Former smokers avoided target images (TIs). Mean reaction time to control images was shorter than to TIs, confirming the attentional avoidance of TIs. Attentional avoidance of TIs and the lower emotional valence of these stimuli may have been a strategy to avoid relapse. Sustained avoidance to smoking-related cues may be a predictor of long-term abstinence. Direct training of AB away from drug cues may improve the results of smoking cessation therapy.     

Symptoms of alcohol dependence and smoking initiation and persistence: A longitudinal study among US adults

Background

A large number of adults report symptoms of, but do not meet diagnostic criteria for, an alcohol use disorder. Yet, little is known about the relationship between symptoms of alcohol use disorders and the initiation and persistence of smoking. This study prospectively examines the relationship between having 1–2 symptoms of alcohol dependence (without abuse) and smoking initiation and persistence as well as nicotine dependence over a 3-year period among adults in the United States.

Methods

Data were drawn from Wave 1 (2001–2002) and Wave 2 (2004–2005) of the National Epidemiologic Survey on Alcohol and Related Conditions. Relationships between Wave 1 symptoms of alcohol dependence, alcohol abuse, and alcohol dependence and initiation and persistence of cigarette smoking and nicotine dependence at Wave 2 were examined using logistic regression analyses. Analyses were adjusted for demographics, mood and anxiety disorders.

Results

Symptoms of alcohol dependence were associated with smoking initiation at Wave 2. There was no association between symptoms of alcohol dependence and smoking persistence. Symptoms of alcohol dependence predicted incident and persistent nicotine dependence. Findings persisted after adjusting for demographic characteristics and mood/anxiety disorders.

Conclusions

Even 1–2 symptoms of alcohol dependence are associated with increased vulnerability to smoking initiation and onset and persistence of nicotine dependence at a similar strength as alcohol use disorders. Efforts at smoking cessation must address problematic alcohol use, even at the subclinical level, in order to improve efficacy.     

Effects of smoking deprivation on smoking behavior and heart rate response in high and low CO absorbing smokers

Short-term deprivation effects on smoking-induced heart rate response and smoking behavior were compared in consistently high and low CO absorbing smokers, suggested to depend differentially on smoking and/or nicotine. The subjects came to the laboratory for two afternoon sessions and smoked at 1 p.m. and at 5 p.m. both after previous free smoking and following afternoon or overnight-morning deprivation. Overnight-morning deprivation decreased presmoking heart rate in both groups similarly, but it increased heart rate response to smoking more in the high than low CO absorbers. Single cigarette tidal CO boosts concomitantly decreased in the high CO absorbers and remained at the habitually low level among the low CO absorbers. Afternoon deprivation had no effects on presmoking heart rate, presmoking tidal CO concentration and tidal CO boost, but increased the heart rate response to smoking in the high CO absorbers. Smoking need and satisfaction as well as puff volume and duration tended to increase after both deprivations slightly more among the high than low CO absorbers. These results are discussed in terms of a differential development of acute tolerance to nicotine in the two groups of smokers which dissipates during smoking abstinence periods.     

Adolescents' rationalizations to continue smoking: The role of disengagement beliefs and nicotine dependence in smoking cessation

Adult smokers were found to reduce cognitive dissonance regarding their smoking behaviour by adhering to rationalizations or justifications to continue smoking, also known as disengagement beliefs. These beliefs were found to be an important barrier with regard to smoking cessation practices. Neither the occurrence of disengagement beliefs, nor its effect on motivation to quit and actual smoking cessation have been studied among adolescent smokers. Therefore, this prospective study among a sample of 363 adolescents examined the extent to which adolescents adhere to disengagement beliefs, and the relations between disengagement beliefs and adolescents' motivation to quit smoking, motivation change and smoking cessation. The association and interplay between disengagement beliefs and level of nicotine dependence was also assessed. Results showed that the degree to which adolescent smokers adhere to disengagement beliefs was similar to that of adults, if not stronger. Higher levels of dependence coincided with stronger adherence to disengagement beliefs. Further, when controlling for nicotine dependence, disengagement beliefs were strongly negatively associated with motivation to quit, but only marginally inversely associated with smoking cessation one year later. Nicotine dependence was the strongest barrier for smoking cessation at follow-up.     

The influence of message framing, intention to quit smoking, and nicotine dependence on the persuasiveness of smoking cessation messages

This study explores the combined effect of message framing, intention to quit smoking, and nicotine dependence on the persuasiveness of smoking cessation messages. Pre- and post-message measures of quit intention, attitude toward smoking cessation, and perceived behavioral control were taken in two separate waves from current cigarette smokers with varying levels of nicotine dependence (N=151). In the second wave, participants were randomly assigned to one of two groups. In the first group, participants read a smoking cessation message which emphasized the benefits of quitting (positive frame). In the second group participants read a message which emphasized the costs of not quitting (negative frame). Results show that smokers' intentions to quit smoking and their level of nicotine dependence jointly influence the persuasiveness of positive and negative message frames. When nicotine dependence and quitting intention are both high, a negative frame works best. Conversely, a positive frame is preferable when nicotine dependence or quitting intention is low. Smokers' level of processing is proposed as the underlying mechanism explaining the different effects of message frames.     

Time-varying effects of smoking quantity and nicotine dependence on adolescent smoking regularity

Background

Little is known about time-varying effects of smoking quantity and nicotine dependence on the regularity of adolescent smoking behavior.

Methods

The sample was drawn from the Social and Emotional Contexts of Adolescent Smoking Patterns Study which followed adolescent smokers over 5 assessment waves spanning 48 months. Participants included former experimenters (smoked <100 cigarettes/lifetime but did not smoke in past 90 days), recent experimenters (smoked <100 cigarettes/lifetime and smoked in past 90 days), and current smokers (smoked >100 cigarettes/lifetime and smoked in past 30 days). Mixed-effects regression models were run to examine the time-varying effects of smoking quantity and nicotine dependence on regularity of smoking behavior, as measured by number of days smoked.

Results

Smoking quantity and nicotine dependence were each found to be significantly associated with regularity of adolescent smoking and the size of each effect exhibited significant variation over time. The effect of smoking quantity decreased across time for each smoking group, while the effect of nicotine dependence increased across time for former and recent experimenters. By the 48-month follow-up, the effects of smoking quantity and nicotine dependence had each stabilized across groups.

Conclusions

This study reveals that smoking quantity and nicotine dependence are not static risk factors for the development of more regular smoking patterns. At low levels of smoking when nicotine dependence symptoms are less common, smoking quantity is a stronger predictor of increased regularity of smoking, while for more experienced smokers, nicotine dependence predicts further increases in regularity.