Cho Y. Lam

Neural substrates of smoking cue reactivity: A meta-analysis of fMRI studies

Reactivity to smoking-related cues may be an important factor that precipitates relapse in smokers who are trying to quit. The neurobiology of smoking cue reactivity has been investigated in several fMRI studies. We combined the results of these studies using activation likelihood estimation, a meta-analytic technique for fMRI data. Results of the meta-analysis indicated that smoking cues reliably evoke larger fMRI responses than neutral cues in the extended visual system, precuneus, posterior cingulate gyrus, anterior cingulate gyrus, dorsal and medial prefrontal cortex, insula, and dorsal striatum. Subtraction meta-analyses revealed that parts of the extended visual system and dorsal prefrontal cortex are more reliably responsive to smoking cues in deprived smokers than in non-deprived smokers, and that short-duration cues presented in event-related designs produce larger responses in the extended visual system than long-duration cues presented in blocked designs. The areas that were found to be responsive to smoking cues agree with theories of the neurobiology of cue reactivity, with two exceptions. First, there was a reliable cue reactivity effect in the precuneus, which is not typically considered a brain region important to addiction. Second, we found no significant effect in the nucleus accumbens, an area that plays a critical role in addiction, but this effect may have been due to technical difficulties associated with measuring fMRI data in that region. The results of this meta-analysis suggest that the extended visual system should receive more attention in future studies of smoking cue reactivity.

A Psychometric Evaluation of Cigarette Stimuli Used in a Cue Reactivity Study

Laboratory studies have demonstrated that cigarette smokers react with significant subjective and autonomic responses (e.g., increased craving and increased heart rate) in the presence of stimuli associated with smoking. Although cue reactivity effects are typically robust, a number of methodological considerations make interpretation and design of cue reactivity studies problematic. Previous research has paid scant attention to the psychometric properties of the cigarette cues presented, and standard cues would enhance comparison and synthesis of studies. In the present study, we evaluated 12 cigarette photos (compared with positive, negative, and neutral photos), used in a separate study, for their ability to evoke self-report of craving in both nicotine-deprived and nondeprived smokers. These photos performed as expected, with cigarette pictures evoking significantly higher craving than neutral pictures and deprived smokers showing a trend toward higher craving than nondeprived smokers. The cigarette picture set was evaluated for internal consistency (Cronbachs alpha = .97) as a 12-item scale and further reduced to multiple 2-item scales with reliability estimates ranging from .70 to .93. A cluster analysis of all pictures showed that, when rated for craving, cigarette pictures clustered together, indicating they had distinct properties compared with positive, negative, and neutral pictures. Effect sizes were calculated for each cigarette picture in both deprived and nondeprived smokers. The craving effect sizes ranged from .57 to .98 for nondeprived smokers, and from .61 to .99 for deprived smokers. The analyses suggest these cigarette pictures have excellent psychometric properties for use in future cue reactivity studies.

Effects of Varenicline and Bupropion Sustained-Release Use Plus Intensive Smoking Cessation Counseling on Prolonged Abstinence From Smoking and on Depression, Negative Affect, and Other Symptoms of Nicotine Withdrawal

IMPORTANCE Given the actions of varenicline tartrate and bupropion hydrochloride sustained-release (SR) on neurobiological targets related to affect and reward, it is thought that the modulation of nicotine withdrawal symptoms may contribute to their effectiveness. OBJECTIVE To assess the relative efficacy of varenicline and bupropion SR plus intensive counseling on smoking cessation and emotional functioning. DESIGN AND SETTING Placebo-controlled randomized clinical trial at a university medical center. PARTICIPANTS In total, 294 community volunteers who wanted to quit smoking. INTERVENTIONS Twelve weeks of varenicline, bupropion SR, or placebo plus intensive smoking cessation counseling (10 sessions, for a total of approximately 240 minutes of counseling). MAIN OUTCOME MEASURES Prolonged abstinence from smoking and weekly measures of depression, negative affect, and other symptoms of nicotine withdrawal. RESULTS Significant differences were found in abstinence at the end of treatment and through the 3-month postquit follow-up visit, favoring both active medications compared with placebo. At the 6-month postquit follow-up visit, only the varenicline vs placebo comparison remained significant. Varenicline use was also associated with a generalized suppression of depression and reduced smoking reward compared with the other treatments, while both active medications improved concentration, reduced craving, and decreased negative affect and sadness compared with placebo, while having little effect (increase or decrease) on anxiety and anger. No differences were noted in self-reported rates of neuropsychiatric adverse events. CONCLUSIONS AND RELEVANCE In a community sample, varenicline exerts a robust and favorable effect on smoking cessation relative to placebo and may have a favorable (suppressive) effect on symptoms of depression and other affective measures, with no clear unfavorable effect on neuropsychiatric adverse events. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00507728.

Effects of an intensive depression-focused intervention for smoking cessation in pregnancy.

OBJECTIVE The objective of this study was to evaluate a depression-focused treatment for smoking cessation in pregnant women versus a time and contact health education control. We hypothesized that the depression-focused treatment would lead to improved abstinence and reduced depressive symptoms among women with high levels of depressive symptomatology. No significant main effects of treatment were hypothesized. METHOD Pregnant smokers (N = 257) were randomly assigned to a 10-week, intensive, depression-focused intervention (cognitive behavioral analysis system of psychotherapy; CBASP) or to a time and contact control focused on health and wellness (HW); both included equivalent amounts of behavioral and motivational smoking cessation counseling. Of the sample, 54% were African American, and 37% met criteria for major depression. Mean age was 25 years (SD = 5.9), and women averaged 19.5 weeks (SD = 8.5) gestation at study entry. We measured symptoms of depression using the Center for Epidemiological Studies-Depression Scale (Radloff, 1977). RESULTS At 6 months posttreatment, women with higher levels of baseline depressive symptoms treated with CBASP were abstinent significantly more often, F(1, 253) = 5.61, p = .02, and had less depression, F(1, 2620) = 10.49, p = .001, than those treated with HW; those with low baseline depression fared better in HW. Differences in abstinence were not retained at 6 months postpartum. CONCLUSIONS The results suggest that pregnant women with high levels of depressive symptoms may benefit from a depression-focused treatment in terms of improved abstinence and depressive symptoms, both of which could have a combined positive effect on maternal and child health.

The Effects of Smoking Deprivation and Nicotine Administration on Emotional Reactivity

Although converging lines of evidence suggest that nicotine and mood are related at a fundamental biological level, this link has not been reliably demonstrated in laboratory studies. In this study, startle probe methodology was used to examine the effects of nicotine administration and deprivation on emotional processes associated with motivation. Smokers (N = 115) completed four laboratory sessions crossing deprivation (12-hr deprived vs. nondeprived) with nicotine spray (active vs. placebo). Participants viewed affective pictures (positive, negative, neutral) and pictures involving cigarette cues, while startle probes were administered. Deprivation decreased startle responding to cigarette cues, suggesting an activation of appetitive processes. Nicotine administration suppressed overall startle responding during deprivation. In addition, during deprivation, random exposure to negative stimuli over two blocks of trials resulted in decreased adaptation of the startle response, suggesting that some sensitization to negative emotional cues may take place during nicotine withdrawal. These effects are consistent with formulations of addiction, stressing that withdrawal may both increase the reinforcement salience of smoking stimuli and decrease habituation to negative emotional stimuli.

Complications of radiotherapy in laryngopharyngeal cancer: Effects of a prospective smoking cessation program

Radiotherapy (XRT) is effective as the primary treatment modality for laryngopharyngeal cancer; however, complications of XRT can result in significant morbidity. Few previous studies have examined the effect of continued smoking on complications of XRT. The authors of this report hypothesized that patients with laryngopharyngeal cancer who successfully quit smoking would have fewer complications of primary XRT.

Brain reactivity to emotional, neutral and cigarette-related stimuli in smokers

Addiction has been described as the pathological usurpation of the neural mechanisms normally involved in emotional processing. Event‐related potentials (ERPs) can provide a non‐invasive index of neural responses associated with the processing of emotionally relevant stimuli and serve as a tool for examining temporal and spatial commonalities between the processing of intrinsically motivating stimuli and drug cues. Before beginning a smoking cessation program, 116 smokers participated in a laboratory session in which dense‐array ERPs (129 sensors) were recorded during the presentation of pictures with emotional (pleasant and unpleasant), neutral and cigarette‐related content. ERP differences among categories were analyzed with use of randomization tests on time regions of interest identified by temporal principal component analysis. Both emotional and cigarette‐related pictures prompted significantly more positivity than did neutral pictures over central, parietal, and frontal sites in the 452–508 ms time window. During the 212–316 ms time window, both pleasant and cigarette‐related pictures prompted less positivity than neutral images did. Cigarette‐related pictures enhanced the amplitude of the P1 component (136–144 ms) above the levels measured in the emotional and neutral conditions. These results support the hypothesis that for smokers, cigarette‐related cues are motivationally relevant stimuli that capture attentional resources early during visual processing and engage brain circuits normally involved in the processing of intrinsically emotional stimuli.

Prequit fMRI Responses to Pleasant Cues and Cigarette-Related Cues Predict Smoking Cessation Outcome

INTRODUCTION 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Combined effects of venlafaxine, nicotine replacement, and brief counseling on smoking cessation.

In this study, 147 smokers were randomly assigned to receive either venlafaxine or placebo in conjunction with behavioral counseling (9 weekly sessions) and transdermal nicotine replacement therapy (22 mg/day). Patients began medication 2 weeks before quitting and continued for 18 weeks after quitting, with the daily dose titrated from 150 to 225 mg. in response to symptoms of negative affect and relapse. The results showed no main effect of treatment on abstinence. Post hoc analysis revealed that both at the end of treatment and at the 1-year follow-up smokers consuming less than a pack of cigarettes a day benefited from the addition of venlafaxine to the treatment regimen. Venlafaxine also reduced negative affect for all smokers for up to 6 weeks postcessation. The findings suggest that venlafaxine could have some role to play in the treatment of lighter smokers, in addition to the expected benefits of nicotine replacement therapy and behavioral counseling.

Predicting Quit Attempts Among Homeless Smokers Seeking Cessation Treatment: An Ecological Momentary Assessment Study

INTRODUCTION Homeless adults are more likely to smoke tobacco and are less likely to successfully quit smoking than smokers in the general population, despite comparable numbers of cessation attempts and desire to quit. To date, studies that have examined smoking cessation in homeless samples have used traditional lab/clinic-based assessment methodologies. Real-time assessment of key variables may provide new insights into the process of quitting among homeless smokers. METHODS The purpose of the current study was to identify predictors of a quit attempt using real-time assessment methodology during the 6 days prior to a scheduled quit attempt among homeless adults seeking care at a shelter-based smoking cessation clinic. Parameters for multiple variables (i.e., motivation for quitting, smoking expectancies, quit self-efficacy, smoking urges, negative affect, positive affect, restlessness, hostility, and stress) were calculated and were used as predictors of biochemically verified quit date abstinence (i.e., ≥13hr abstinent) using logistic regression analyses. RESULTS Participants (n = 57) were predominantly male (59.6%), non-White (68.4%), and smoked an average of 18 cigarettes per day. A total of 1,132 ecological momentary assessments (83% completion rate) were collected at random times (i.e., up to 4 assessments/day) during the 6 days prior to a scheduled quit attempt. Results indicated that declining (negative slope) negative affect, restlessness, and stress predicted quit date abstinence. Additionally, increasing positive coping expectancies across the prequit week predicted quit date abstinence. CONCLUSIONS Study findings highlight multiple variables that may be targeted during the precessation period to increase smoking cessation attempts in this difficult to treat population of smokers.