Convergent Evidence that Choline Acetyltransferase Gene Variation is Associated with Prospective Smoking Cessation and Nicotine Dependence

The ability to quit smoking is heritable, yet few genetic studies have investigated prospective smoking cessation. We conducted a systems-based genetic association analysis in a sample of 472 treatment-seeking smokers of European ancestry after 8 weeks of transdermal nicotine therapy for smoking cessation. The genotyping panel included 169 single-nucleotide polymorphisms (SNPs) in 7 nicotinic acetylcholine receptor subunit genes and 4 genes in the endogenous cholinergic system. The primary outcome was smoking cessation (biochemically confirmed) at the end of treatment. SNPs clustered in the choline acetyltransferase (ChAT) gene were individually identified as nominally significant, and a 5-SNP haplotype (block 6) in ChAT was found to be significantly associated with quitting success. Single SNPs in ChAT haplotype block 2 were also associated with pretreatment levels of nicotine dependence in this cohort. To replicate associations of SNPs in haplotype blocks 2 and 6 of ChAT with nicotine dependence in a non-treatment-seeking cohort, we used data from an independent community-based sample of 629 smokers representing 200 families of European ancestry. Significant SNP and haplotype associations were identified for multiple measures of nicotine dependence. Although the effect sizes in both cohorts are modest, converging data across cohorts and phenotypes suggest that ChAT may be involved in nicotine dependence and ability to quit smoking. Additional sequencing and characterization of ChAT may reveal functional variants that contribute to nicotine dependence and smoking cessation.     

Childhood Poverty and Stress Reactivity Are Associated with Aberrant Functional Connectivity in Default Mode Network

Convergent research suggests that childhood poverty is associated with perturbation in the stress response system. This might extend to aberrations in the connectivity of large-scale brain networks, which subserve key cognitive and emotional functions. Resting-state brain activity was measured in adults with a documented history of childhood poverty (n=26) and matched controls from middle-income families (n=26). Participants also underwent a standard laboratory social stress test and provided saliva samples for cortisol assay. Childhood poverty was associated with reduced default mode network (DMN) connectivity. This, in turn, was associated with higher cortisol levels in anticipation of social stress. These results suggest a possible brain basis for exaggerated stress sensitivity in low-income individuals. Alterations in DMN may be associated with less efficient cognitive processing or greater risk for development of stress-related psychopathology among individuals who experienced the adversity of chronic childhood poverty.     

Smoking Cessation with Hospital Employees: An Example of Worksite Smoking Cessation

Fifteen hospital employees and two patients completed a smoking cessation treatment program of 10 1-hour sessions. At 6-month follow-up, 13 of the employees were still working at the hospital and were able to be contacted. Of those employees who completed treatment and were still employed, seven were not smoking, a success rate of 53%. Worksite smoking cessation programs are viewed not ońly as cost-effective ways for hospitals to help their employees stop but as a way of encouraging their employees to model more healthy behavior to patients.     

Efficacy of an Alternative Smoking Cessation Treatment

ABSTRACT

The authors tested the effectiveness of a smoking cessation treatment called auricular therapy that involves the delivery of electrical pulses to specific points on the outer ear. They explored the following question: Do patients undergoing auricular therapy demonstrate greater quit rates in comparison to patients assigned to a control group (i.e., undergoing sham auricular therapy)? Analysis revealed that genuine auricular therapy and placebo group differences on all measures of smoking behavior and nicotine withdrawal symptoms did not approach significance. Abstinence rates among patients in both groups were low and groups did not obtain significantly different scores on the Fagerstrom Test for Nicotine Dependence at all assessment points.     

Common and Unique Biological Pathways Associated with Smoking Initiation/Progression, Nicotine Dependence, and Smoking Cessation

Twin and family studies reveal a significant genetic contribution to the risk of smoking initiation and progression (SI/P), nicotine dependence (ND), and smoking cessation (SC). Further, numerous genes have been implicated in these smoking-related behaviors, especially for ND. However, no study has presented a comprehensive and systematic view of the genetic factors associated with these important smoking-related phenotypes. By reviewing the literature on these behaviors, we identified 16, 99, and 75 genes that have been associated with SI/P, ND, and SC, respectively. We then determined whether these genes were enriched in pathways important in the neuronal and brain functions underlying addiction. We identified 9, 21, and 13 pathways enriched in the genes associated with SI/P, ND, and SC, respectively. Among these pathways, four were common to all of the three phenotypes, that is, calcium signaling, cAMP-mediated signaling, dopamine receptor signaling, and G-protein-coupled receptor signaling. Further, we found that serotonin receptor signaling and tryptophan metabolism pathways were shared by SI/P and ND, tight junction signaling pathway was shared by SI/P and SC, and gap junction, neurotrophin/TRK signaling, synaptic long-term potentiation, and tyrosine metabolism were shared between ND and SC. Together, these findings show significant genetic overlap among these three related phenotypes. Although identification of susceptibility genes for smoking-related behaviors is still in an early stage, the approach used in this study has the potential to overcome the hurdles caused by factors such as genetic heterogeneity and small sample size, and thus should yield greater insights into the genetic mechanisms underlying these complex phenotypes.     

Smoking Cessation for Patients with Cardiovascular Disease

Tobacco use remains the major preventable cause of early mortality and morbidity in the US and is a major risk factor for cardiovascular disease (CVD). Quitting smoking rapidly reduces the risk of cardiovascular events. In this review, we identify and discuss best approaches to assist smoking cessation among patients with CVD. Establishing office systems that reliably identify smokers to healthcare providers is an essential first step. Once the patient is identified as a smoker, providers should inquire about their willingness to quit and advise them to quit or provide motivation to get ready to make a quit attempt. Behavioral (counseling) and pharmacologic (nicotine replacement and non-nicotine medications) treatments double or triple long-term cessation rates and should be offered in combination to all patients with CVD who use tobacco. More intensive behavioral therapy is more effective and should be delivered when possible. The choice of pharmacotherapy will depend upon the clinical history of the patient and patient preference. Nicotine replacement and sustained release bupropion (bupropion SR) are first-line treatments for smoking cessation. Nicotine patches have been studied extensively in patients with stable CVD and have been shown to be safe. Bupropion SR has relatively few cardiovascular adverse effects and may be especially useful for patients with CVD; its safety is currently being studied. Special consideration is needed for hospitalized patients with acute coronary syndromes (e. g. myocardial infarction and unstable angina). The safety of pharmacotherapy in the acute setting is not yet established. Behavioral interventions, however, are very effective and should be delivered to all hospitalized smokers. Finally, it is important to create a clinical environment that is supportive of treating patients with tobacco dependence. Simple changes in office and hospital routines and procedures (routine screening to identify smokers, prompts to encourage intervention and links to more intensive tobacco dependence treatment programs) will substantially improve the identification, treatment, and outcomes of patients with CVD who use tobacco.     

Improved Depressive Symptoms in Adults with Schizophrenia During a Smoking Cessation Attempt with Varenicline and Behavioral Therapy

Objective: Smoking prevalence rates are elevated in individuals with schizophrenia spectrum disorders (SSD) compared with the general population, with attendant disproportionate smoking-related morbidity and mortality. Pharmacotherapies that improve abstinence rates in this population are underutilized, partly due to concerns about neuropsychiatric safety, particularly for those with comorbid depression or prior suicide attempt. Prospective assessment of the psychiatric safety profile of varenicline in those with SSD is needed. Methods: Adult smokers with SSD entered a 12-week trial of varenicline and behavioral therapy for smoking cessation. Depressive symptoms were assessed with the Calgary Depression Scale for Schizophrenia (CDSS) at baseline and weekly thereafter. Participants with baseline and one or more postbaseline CDSS assessments, n = 179, were included in a secondary analysis of change in depressive symptoms with varenicline treatment, adjusting for abstinence status and baseline depressive symptoms. Results: Twenty-seven percent of participants had a CDSS score at baseline consistent with current major depressive disorder, and more than half had a prior suicide attempt. Forty-one percent (74/179) achieved two or more weeks of continuous abstinence at the end of treatment. CDSS scores declined 31% during the 12-week treatment period. Controlling for baseline CDSS scores, depressive symptoms declined over time in those who completed the trial, independent of abstinence status, and either declined or remained unchanged in those with major depressive disorder or prior suicide attempt or who were taking antidepressant medication. Those who did not complete the trial had no change in depressive symptoms. Discussion: Depressive symptoms declined in adults with schizophrenia during 12 weeks of varenicline treatment and cognitive behavioral therapy, independent of tobacco abstinence. Smokers with SSD who have significant depressive symptoms may be successful in smoking cessation attempts with pharmacotherapeutic aids such as varenicline while maintaining stable psychiatric symptoms. This is a secondary analysis of data collected as part of a clinical trial registered as NCT00621777, at www.clinicaltrials.gov.     

Prognosis in a Smoking Cessation Program

In an attempt to develop a heuristic model of outcome in smoking cessation programs, pretreatment measures of smoking behavior, smoking severity, chronicity of smoking, addictive liability, and health functioning were utilized in order to predict outcome on the number of cigarettes smoked and carbon monoxide (CO) levels at 6-month follow-up. The results of multiple regression analyses supported the view that addictive liability, as indicated by high nicotine ingestion, contributed to higher levels of smoking on follow-up. Poor health status also predicted higher smoking levels on follow-up, as did pretreatment measures of the number of cigarettes smoked per day. However, measures of smoking severity (carbon monoxide and thiocyanate levels) at pretreatment were negatively related to smoking behavior on follow-up. The number of years of smoking history was negatively related to smoking behavior on follow-up. These results need to be cross-validated with larger samples, but the results suggest that prognosis in smoking cessation is worsened     

Withdrawal-Associated Increases and Decreases in Functional Neural Connectivity Associated with Altered Emotional Regulation in Alcoholism

Alcoholic patients who have undergone multiple detoxifications/relapses show altered processing of emotional signals. We performed functional magnetic resonance imaging during performance of implicit and explicit versions of a task in which subjects were presented with morphs of fearful facial emotional expressions. Participants were abstaining, multiply detoxified (MDTx; n=12) or singly detoxified patients (SDTx; n=17), and social drinker controls (n=31). Alcoholic patients were less able than controls to recognize fearful expressions, and showed lower activation in prefrontal areas, including orbitofrontal cortex and insula, which mediate emotional processing. The decrease in activation was greater in MDTx patients who also showed decreased connectivity between insula and prefrontal areas, and between amygdala and globus pallidus. In the explicit condition, the strength of connectivity between insula and areas involved in regulation of emotion (inferior frontal cortex and frontal pole) was negatively correlated with both the number of detoxifications and dependency (measured by the severity of alcohol dependency (SADQ) and control over drinking score (Impaired Control questionnaire, ICQ)). In contrast, increased connectivity was found between insula and the colliculus neuronal cluster, and between amygdala and stria terminalis bed nucleus. In the implicit condition, number of detoxifications and ICQ score correlated positively with connectivity between amygdala and prefrontal cortical areas involved in attentional and executive processes. Repeated episodes of detoxification from alcohol are associated with altered function both in fear perception pathways and in cortical modulation of emotions. Such changes may confer increased sensitivity to emotional stress and impaired social competence, contributing to relapse.     

Implementing Smoking Cessation Programmes in Prison Settings

In spite of abundant evidence as to the adverse health problems of tobacco use over the past half century, progress towards tobacco control in prisons have been minimal. Lack of political will, boredom, stress, imprisonment-related deprivation, sub-optimal demographic characteristics of prisoners, and the unavailability of formal funding mechanisms for smoking cessation support - including nicotine replacement therapy - are common reasons for this minimal progress. The author suggests that another important obstacle is a limited adoption of smoking cessation interventions that are specifically tailored for use in prison cohorts. Since 2000, the author developed and implemented smoking cessation programmes, using a Social Marketing framework, in eight Australian prisons as part of a tobacco control project. Based on his experience, the author discusses issues to consider in implementing such programmes in other prisons. Prison-based smoking cessation programmes remain a neglected but important health intervention. Adaptation of Social Marketing techniques may facilitate the feasibility and effectiveness of such programmes.     

Smoking Cessation Outcomes and Predictors Among Individuals With Co-occurring Substance Use and/or Psychiatric Disorders

Objective: Individuals with substance use and psychiatric disorders have a high prevalence of tobacco use disorders and are disproportionately affected by tobacco-related morbidity and mortality. However, it is unclear how having co-occurring disorders affects tobacco cessation. Our aim was to examine smoking cessation outcomes and relevant predictors of smoking cessation among smokers with substance use and/or psychiatric disorders. Methods: Data from medical records of 674 participants in a tobacco treatment program within mental health and addictions services in Vancouver, Canada, were analyzed. The 26-week treatment program included an 8-week structured behavioral counseling group, an 18-week support group, and 26 weeks of no-cost pharmacotherapy. Information on demographics, tobacco use and history, type of pharmacotherapy received, nicotine dependence, importance of and confidence in quitting smoking, expired carbon monoxide level, substance use and psychiatric disorder history, and total program visits were gathered. Results: Approximately 67% (n = 449) of participants had co-occurring substance use and psychiatric disorders, while 20% (n = 136) had substance use disorder only, 10% (n = 67) had psychiatric disorder only, and 3% (n = 22) had tobacco dependence only. Rates of tobacco cessation (i.e., 7-day point prevalence of abstinence verified by expired carbon monoxide of ≤8 ppm) by group in the 522 people who completed treatment were as follows: 38.2% for those with co-occurring disorders, 47.1% for those with tobacco dependence only, 47.1% for those with substance use disorder only, and 41.8% for those with psychiatric disorder only. Length of treatment was a significant predictor of smoking cessation for those with co-occurring disorders and substance use disorder only. In the final stratified multivariate analysis, for individuals with co-occurring disorders, having an opiate use disorder (as compared to an alcohol use disorder) and higher nicotine dependence scores at baseline were predictive of poor cessation outcomes, while greater length of treatment was predictive of successful smoking cessation. Conclusions: Tobacco cessation treatment for individuals with co-occurring substance use and psychiatric disorders is likely to be as effective as for smokers with either disorder alone. Treatment duration predicts success among these smokers so strategies to enhance engagement and retention are needed.     

伐尼克兰在慢性阻塞性肺疾病患者戒烟治疗中的作用

［摘要］目的评估伐尼克兰戒除轻中度慢性阻塞性肺疾病（COPD）吸烟患者尼古丁依赖（烟瘾）的有效性和安全性。方法COPD尼古丁依赖患者50例,分为治疗组和对照组各25例,采用随机、双盲、安慰药对照,治疗组给予伐尼克兰0.5～2.0 mg•d 1;对照组给予等剂量的安慰药。治疗期和治疗后的随访期均为12周。结果治疗组和对照组在治疗期最后4周的持续戒断患者分别为13和8例;第9～24周的持续戒断患者分别为8和5例;第12周的7 d时点戒烟患者分别为14和8例;第24周7 d时点戒烟患者分别为9和6例;发生不良反应均为2例。结论伐尼克兰用于戒除轻中度COPD患者尼古丁依赖安全,有效。     

Characteristics Affecting Successful Outcome in the Cessation of Smoking

In this study predictors of successful smoking cessation among 166 clients of a smoking cessation program were examined via multiple regression analyses. Results showed that seven significant predictors accounted for 25% of the variance in successful smoking cessation. Abstainers tended to have higher incomes, to rate pregnancy as a motivation more highly, to have made fewer previous attempts to quit, to be low on habit smoking, to crave cigarettes more in low-arousal situations, to be stimulus reducers, and to be older.     

Racial and Ethnic Differences in Predictors of Smoking Cessation

Racial/ethnic differences in the determinants of smoking cessation could have important treatment implications. The current study examined racial/ethnic differences in smoking cessation, prospective predictors of cessation, and whether the predictive ability of these factors differed by race/ethnicity. Participants were 709 employed adults recruited through the National Rural Electric Co-op Association or through natural gas pipeline corporations. Data were collected in 1990 and 1994. Although race/ethnicity was not predictive of abstinence, Hispanic, African American, and White smokers displayed differential on tobacco-, alcohol-, and work-related variables. These racial/ethnic differences highlight the specific factors that should be considered when providing smoking cessation treatment to specific populations. Limitations are noted.     

Family Discord is Associated with Increased Substance Use for Pregnant Substance Users

Childhood abuse and partner violence are associated with prenatal substance abuse, but the potential impact of current family discord, which reflects broader family relationships and encompasses problems less severe than violence, has had little evaluation in pregnant substance users. Using data from 196 pregnant substance users participating in a NIDA Clinical Trials Network randomized clinical trial, we examined the relationship of baseline family discord to substance use and treatment session attendance. Family discord was assessed using items from the family composite of the Addiction Severity Index. Substance use was assessed by the Substance Use Calendar and urine drug screens (UDS). Assessments were weekly for four weeks and at two- and four-month post-randomization. Women with family discord were more likely to report living with a problematic substance user, reported a higher percentage of substance use days throughout each study phase, had a greater proportion of positive UDS over the four-month study period, and attended more weeks of treatment during the first month. Specific treatment interventions targeting pregnant women with family discord may be warranted.     

Acute CO Poisoning is Associated with Impaired Fibrinolysis and Increased Thrombin Generation

Carbon monoxide (CO) poisoning is a leading cause of unintentional poisoning deaths in many countries. In ex vivo studies, CO released from carbon monoxide‐releasing molecules has been shown to attenuate fibrinolysis via increased alpha‐2‐antiplasmin activity. Hypofibrinolysis is associated with coronary ischaemia, which is also commonly observed in CO poisoning. We examined fibrin clot properties in acutely poisoned CO patients. Ex vivo plasma fibrin clot permeability, turbidimetry and efficiency of fibrinolysis were investigated in 48 patients and controls matched for age and sex. CO‐poisoned patients had 11.6% longer clot lysis time than the controls (p < 0.0001). No intergroup differences in clot permeability or turbidimetric variables were observed. Plasma tissue‐type plasminogen antigen (tPA), plasminogen activator inhibitor‐1 (PAI‐1) antigen and activity and F1.2 prothrombin fragments were higher in the patients than in the controls (all p < 0.0001). Plasma tPA activity was lower in the CO‐poisoned group. Multiple linear regression showed that a thrombin generation marker, F1.2, is the strongest predictor of clot lysis time, followed by PAI‐1 activity and carboxyhaemoglobin levels. In conclusion, this report is the first to demonstrate that acute CO poisoning in human beings is linked to increased thrombin generation and impaired fibrinolysis, which might contribute to ischaemic complications.     

Predictors of Smoking Cessation in a Sample of Italian Smokers

In this study we identify several pretreatment characteristics which predict abstinence at 6 months. Moreover, the persistence of withdrawal discomfort and of an increased frequency of night awakenings during the first month of abstinence, together with a tendency to “slip” during Weeks II-IV, strongly predicted relapse. Our results suggest that: 1) Predictors of outcome cannot be automatically extended from one cultural context to another; 2) a careful assessment of certain variables, made while the patient is still under treatment, provides significant prognostic hints; 3) ex-smokers' sleeping and dreaming function has been ignored by the literature, whereas they may well be involved into the maintenance of the drug-free state.