Nicotine dependence in the United States: prevalence, trends, and smoking persistence.

BACKGROUND: The prevalence of smoking in the United States has been closely monitored. However, little is known about the epidemiology of nicotine dependence. We studied DSM-III-R nicotine dependence in the United States, trends across cohorts, and the role of nicotine dependence in smoking persistence. METHODS: The Tobacco Supplement to the National Comorbidity Survey was administered to a representative subset of 4414 persons aged 15 to 54 years. The World Health Organization's Composite International Diagnostic Interview was used to assess nicotine dependence. RESULTS: Lifetime prevalence of nicotine dependence was 24%, nearly half of those who had ever smoked daily for a month or more. The highest risk for nicotine dependence occurred in the first 16 years after daily smoking began, at which point the rate declined and continued at a slower pace for several years. Nicotine dependence increased the risk of smoking persistence, with an odds ratio (OR) of 2.2 (95% confidence interval [CI], 1.6-3.0). Members of the most recent cohort, who were 15 to 24 years of age at the time of the survey, were the least likely to smoke daily, but those who smoked had the highest risk of dependence: OR for daily smoking in the most recent vs earliest cohort was 0.7 (95% CI, 0.5-0.9), and for dependence among smokers, 7.2 (95% CI, 5.0-10.4). CONCLUSIONS: Despite evidence that nicotine dependence is the leading preventable cause of death and morbidity, it remains a common psychiatric disorder. Smoking cessation and the decline in uptake in recent years varied across subgroups of the population.     

Nicotine dependence and psychiatric disorders in the United States: results from the national epidemiologic survey on alcohol and related conditions

BACKGROUND: No information is available on the co-occurrence of DSM-IV nicotine dependence and Axis I and II psychiatric disorders in the US population. OBJECTIVES: To present national data on the co-occurrence of current DSM-IV nicotine dependence and other psychiatric disorders by sex and to estimate the burden of all US tobacco consumption carried by nicotine-dependent and psychiatrically ill individuals. DESIGN: Face-to-face interviews. SETTING: The United States. PARTICIPANTS: Household and group-quarters adults (N = 43 093). MAIN OUTCOME MEASURES: Prevalence and comorbidity of current nicotine dependence and Axis I and II disorders and the percentage of cigarettes consumed in the United States among psychiatrically vulnerable subgroups. RESULTS: Among US adults, 12.8% (95% confidence interval, 12.0-13.6) were nicotine dependent. Associations between nicotine dependence and specific Axis I and II disorders were all strong and statistically significant (P<.05) in the total population and among men and women. Nicotine-dependent individuals made up only 12.8% (95% confidence interval, 12.0-13.6) of the population yet consumed 57.5% of all cigarettes smoked in the United States. Nicotine-dependent individuals with a comorbid psychiatric disorder made up 7.1% (95% confidence interval, 6.6-7.6) of the population yet consumed 34.2% of all cigarettes smoked in the United States. CONCLUSIONS: Nicotine-dependent and psychiatrically ill individuals consume about 70% of all cigarettes smoked in the United States. The results of this study highlight the importance of focusing smoking cessation efforts on individuals who are nicotine dependent, individuals who have psychiatric disorders, and individuals who have comorbid nicotine dependence and other psychiatric disorders. Further, awareness of industry segmentation strategies can improve smoking cessation efforts of clinicians and other health professionals among all smokers and especially among the most vulnerable.     

Smoking cessation services in U.S. methadone maintenance facilities

OBJECTIVES: Most patients in drug treatment smoke cigarettes. This study established the prevalence and types of nicotine dependence services offered in methadone and other opioid treatment clinics in the United States. METHODS: A cross-sectional survey was conducted of all outpatient methadone maintenance clinics in the United States. One person in a leadership position from each clinic was surveyed. The 20-minute survey was collected by phone, fax, or mail, according to responder preference. RESULTS: Fifty-nine percent of the clinics (408 of 697 clinics) responded. The sample was very similar to all outpatient methadone maintenance clinics in the United States in size, region, and ownership. In the 30 days before the survey, respondents reported that their clinics provided the following services to at least one patient: 73 percent provided brief advice to quit, 18 percent offered individual or group smoking cessation counseling, and 12 percent prescribed nicotine replacement therapy. However, the services were provided to very few patients. Clinics with written guidelines that required them to address smoking were much more likely to provide services than those without guidelines. Private for-profit clinics were significantly less likely than public or private nonprofit clinics to treat nicotine dependence. Most respondents (77 percent) reported that their staff were interested in receiving training in nicotine dependence treatment, and more than half (56 percent) had at least one staff member ("champion") with a strong interest in treating nicotine dependence. CONCLUSIONS: A vast majority of methadone patients smoke; yet in the 30 days before the survey only one out of three facilities provided counseling to any patients and only one out of ten prescribed nicotine replacement therapy to any patients. A dual strategy of requiring clinics to provide comprehensive nicotine dependence services and training staff to provide these services may provide the incentive and support necessary for the widespread adoption of treatment for nicotine dependence in methadone facilities.     

Genetic variability in nicotinic acetylcholine receptors and nicotine addiction: converging evidence from human and animal research

Tobacco smoking is a leading preventable cause of death in the United States and produces a major health and economic burden. Although the majority of smokers want to quit, few are successful. These data highlight the need for additional research into the neurobiology of tobacco dependence. Addiction to nicotine, the main psychoactive component of tobacco, is influenced by multiple factors that include individual differences in genetic makeup. Twin studies have demonstrated that genetic factors can influence vulnerability to nicotine addiction, and subsequent research has identified genes that may alter sensitivity to nicotine. In humans, genome-wide and candidate gene association studies have demonstrated that genes encoding nicotinic acetylcholine receptor (nAChR) proteins are associated with multiple smoking phenotypes. Similarly, research in mice has provided evidence that naturally occurring variability in nAChR genes is associated with changes in nicotine sensitivity. Furthermore, the use of genetic knockout mice has allowed researchers to determine the nAChR genes that mediate the effects of nicotine, whereas research with knockin mice has demonstrated that changes to nAChR genes can dramatically alter nicotine sensitivity. This review will examine the genetic factors that alter susceptibility to nicotine addiction, with an emphasis on the genes that encode nAChR proteins.     

The association between high nicotine dependence and severe mental illness may be consistent across countries

BACKGROUND: Studies all over the world suggest that severe mental illness, including schizophrenia and mood disorders, is associated with tobacco smoking. This study, combining samples from the United States and Spain, had 3 objectives: (1) to test the hypothesis that severely mentally ill patients who smoke are more likely to have a high nicotine dependence when compared with control smokers, (2) to compare frequencies of high nicotine dependence in controls in both countries, and (3) to compare frequencies of high nicotine dependence in severely mentally ill patients in both countries. METHOD: Scores on the Fagerstr?m Test for Nicotine Dependence (FTND) for 4 samples of current daily smokers were analyzed. The sample sizes of the U.S. and Spanish control groups were 129 and 646 subjects, respectively. The diagnoses for the U.S. patients were DSM-IV schizophrenia, 74% (89/120), and DSM-IV mood disorders, 26% (31/120). The diagnoses for the Spanish patients were DSM-IV schizophrenia, 87% (173/199), and DSM-III-R mood disorders, 13% (26/199). High nicotine dependence (FTND score > or = 6) was the dependent variable in 5 logistic regression analyses. RESULTS: The main findings were that (1) severely mentally ill patients had significantly higher frequencies of high nicotine dependence than controls (odds ratio [OR] = 10.59, 95% CI = 7.31 to 15.34) even after controlling for gender, country, interaction between country and mental illness, and age; (2) U.S. controls had significantly higher frequencies of high nicotine dependence than Spanish controls (OR = 3.18, 95% CI = 2.02 to 5.00); and (3) U.S. and Spanish patients did not have significantly different frequencies of high nicotine dependence. CONCLUSION: New studies, specially designed to test for transcultural differences in nicotine dependence, are needed to verify that nicotine dependence in severely mentally ill patients is consistently high and similar in different countries.     

A DRD2 and ANKK1 haplotype is associated with nicotine dependence

To test the importance of the dopamine D2 receptor (DRD2) region in nicotine dependence, 150 smokers and 228 controls were genotyped for the DRD2 C957T, -141delC and ANKK1 TaqIA polymorphisms (rs6277, rs1799732 and rs1800497, respectively). The -141delC SNP did not show any association but both the C957T and TaqIA SNPs showed association at the allele, genotype, haplotype and combined genotype levels. The 957C/TaqI A1 haplotype was more than 3.5 times as likely to be associated with nicotine dependence compared with the 957T/TaqI A1 haplotype (P=0.003). Analysis of the combined genotypes of both SNPs revealed that individuals who were homozygous for the 957C-allele (CC) and had either one or two copies of the TaqI A1-allele were 3.3 times as likely to have nicotine dependence compared to all other genotype combinations (P=0.0003) and that these genotypes accounted for approximately 13% of the susceptibility to nicotine addiction in our population. Our findings suggest that the DRD2 C957T polymorphism and the ANKK1 TaqIA polymorphism are key contributors to the genetic susceptibility to nicotine dependence.     

Alpha-5/alpha-3 nicotinic receptor subunit alleles increase risk for heavy smoking

Twin studies indicate that additive genetic effects explain most of the variance in nicotine dependence (ND), a construct emphasizing habitual heavy smoking despite adverse consequences, tolerance and withdrawal. To detect ND alleles, we assessed cigarettes per day (CPD) regularly smoked, in two European populations via whole genome association techniques. In these approximately 7500 persons, a common haplotype in the CHRNA3-CHRNA5 nicotinic receptor subunit gene cluster was associated with CPD (nominal P=6.9 x 10(-5)). In a third set of European populations (n= approximately 7500) which had been genotyped for approximately 6000 SNPs in approximately 2000 genes, an allele in the same haplotype was associated with CPD (nominal P=2.6 x 10(-6)). These results (in three independent populations of European origin, totaling approximately 15 000 individuals) suggest that a common haplotype in the CHRNA5/CHRNA3 gene cluster on chromosome 15 contains alleles, which predispose to ND.     

Posttraumatic stress disorder and the incidence of nicotine,alcohol, and other drug disorders in persons who have experienced trauma

BACKGROUND: We examine whether exposure to traumatic events increases the risk for nicotine dependence or alcohol or other drug use disorders, independent of posttraumatic stress disorder (PTSD). METHODS: Data come from a longitudinal epidemiologic study of young adults in southeast Michigan. Prospective data covering a 10-year period and retrospective lifetime data gathered at baseline were used to estimate the risk for onset of substance use disorders in persons with PTSD and in persons exposed to trauma without PTSD, compared with persons who have not been exposed to trauma. The National Institute of Mental Health Diagnostic Interview Schedule for DSM-III-R was used. Logistic regression was used to analyze the prospective data, and Cox proportional hazards survival analysis with time-dependent variables was applied to the lifetime data. RESULTS: The prospective and retrospective data show an increased risk for the onset of nicotine dependence and drug abuse or dependence in persons with PTSD, but no increased risk or a significantly (P =.004) lower risk (for nicotine dependence, in the prospective data) in persons exposed to trauma in the absence of PTSD, compared with unexposed persons. Exposure to trauma in either the presence or the absence of PTSD did not predict alcohol abuse or dependence. CONCLUSIONS: The findings do not support the hypothesis that exposure to traumatic events per se increases the risk for substance use disorders. A modestly elevated risk for nicotine dependence might be an exception. Posttraumatic stress disorder might be a causal risk factor for nicotine and drug use disorders or, alternatively, the co-occurrence of PTSD and these disorders might be influenced by shared risk factors other than traumatic exposure.     

Neurogenetic determinants and mechanisms of addiction to nicotine and smoked tobacco

The single most preventable cause of disease, disability, and death in the United States is tobacco use. Decades of study show that the risk of becoming addicted to smoked cigarettes varies greatly amongst individuals and is heritable, yet environmental factors are also important contributors. In this review, we consider a wide range of methodologies and key published reports that have defined the inheritance of different stages of nicotine‐dependent smoking behavior, including preference, initiation, regular use, withdrawal and dependence as well as cessation and relapse. Major findings from both animal and human studies are discussed. Current findings converge primarily on the role of nicotinic cholinergic receptor subunits, although other neurotransmitter systems as well as nicotine metabolism enzymes are implicated. Various stages of nicotine addiction may share common genetic mechanisms, yet several lines of evidence indicate that each stage also has its own unique genetic determinants. Studies on the heritability of smoking initiation demonstrate substantial evidence for gene–environment interaction, although the precise molecular genetic mechanism(s) remains unknown. Considering the relatively few genes identified so far and the small to modest fraction of the variance in risk for a particular smoking phenotype (e.g., smoking initiation in late adolescence) attributable to these genes, a large gap remains to be filled in order to account for the heritability of key phenotypes involved in each stage of addiction to smoked tobacco. Looking forward, new research strategies involving both human and animal studies will produce the fundamental genetic insights that are the foundation for the precision medical treatment of individuals addicted to smoked tobacco.     

The μ-opioid receptor gene and smoking initiation and nicotine dependence

The gene encoding the mu-opioid receptor (OPRM1) is reported to be associated with a range of substance dependence. Experiments in knockout mice indicate that the mu-opioid receptor may mediate reinforcing effects of nicotine. In humans, opioid antagonist naltrexone may reduce the reinforcing effects of tobacco smoking. Additionally, the OPRM1 gene is located in a region showing linkage to nicotine dependence. The OPRM1 is thus a plausible candidate gene for smoking behavior. To investigate whether OPRM1 contributes to the susceptibility of smoking initiation and nicotine dependence, we genotyped 11 SNPs in the gene for 688 Caucasian subjects of lifetime smokers and nonsmokers. Three SNPs showed nominal significance for smoking initiation and one reached significance for nicotine dependence. The global test for three-marker (rs9479757-rs2075572-rs10485057) haplotypes was significant for smoking initiation (p = 0.0022). The same three-marker haplotype test was marginal (p = 0.0514) for nicotine dependence. These results suggest that OPRM1 may be involved in smoking initiation and nicotine dependence.     

Nicotine dependence, major depression, and anxiety in young adults.

To determine whether nicotine dependence, classified by level of severity, was associated with other substance dependence, major depression, and anxiety disorders, we studied a random sample of 1007 young adults in the Detroit (Mich) area using the National Institute of Mental Health Diagnostic Interview Schedule, revised according to DSM-III-R. The systematic coverage of DSM-III-R criteria of nicotine dependence provides an unprecedented opportunity to separate persons with nicotine dependence from the larger class of persons with a history of smoking and to examine the prevalence of psychiatric disorders among persons with nicotine dependence and among nondependent smokers. The lifetime prevalence of nicotine dependence was 20%. Nicotine dependence was associated with alcohol, cannabis, and cocaine dependence. Controlling for the effects of other substance dependencies, persons with nicotine dependence had higher rates of major depression and anxiety disorders. The strength of these associations varied by level of severity of nicotine dependence. Nondependent smokers had higher rates of other substance dependencies, but not of major depression or anxiety disorders.     

Protective effects of timolol against the neuronal damage induced by glutamate and ischemia in the rat retina

Smoking is considered the leading cause of preventable death in the United States, but studies in animals suggest that nicotine is only weakly reinforcing. The maintenance of a dangerous habit by a weakly reinforcing agent has been the topic of some dispute. Using a two-lever "choice" self-administration procedure developed in our laboratory, we evaluated drug preferences as an index of relative reward strength for nicotine versus cocaine in nicotine-trained rats. Rats were initially exposed to each drug separately in single-lever self-administration sessions and then allowed to choose between them in a two-lever choice test session offering both drugs. When offered choices between different nicotine doses [8, 25, and 75 microg/kg/injection (inj), free base], rats responded approximately equally for any dose, regardless of which doses were compared. Rats clearly preferred 267 or 800 microg/kg/inj cocaine hydrochloride to any of the nicotine doses. These results indicate that cocaine has greater reward strength than nicotine and supports previous findings that self-administering rats seek to maximize reward magnitude regardless of the self-administered drug or training history. It is possible that dependence elevates nicotine's reward magnitude or nicotine addiction may rely more importantly upon negative rather than pure positive reinforcement.     

The relationship between nicotine cessation and mental disorders in a nationally representative sample

The objective of this study was to examine the relationship between Axis I and II mental disorders, quality of life, and nicotine dependence cessation in a nationally representative sample. Data came from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a nationally representative survey of adults in the United States (N = 34,653). People who met DSM-IV criteria for nicotine dependence previously but who had abstained from nicotine in the last year (nicotine cessation) were compared to people currently dependent on nicotine as well as lifetime abstainers using multivariate logistic regression. Outcomes of interest included DSM-IV Axis I and II mental disorders, treatment seeking for mental disorders, and quality of life measures. In adjusted models, individuals who ceased nicotine use in the last year were less likely to have past-year mood [adjusted odds ratio (AOR) = 0.64; 95% confidence interval (CI) 0.50–0.82, p < 0.001] and substance use disorders (AOR = 0.65, 95% CI 0.52–0.82, p < 0.001) compared to those with current nicotine dependence. They were also less likely to have narcissistic and borderline personality disorders. Compared to those with current nicotine dependence, cessation was associated with an improved quality of life, both physically (beta = 1.65; standard error 0.40, p < 0.001) and mentally (beta = 2.17, standard error 0.39, p < 0.001). In conclusion, nicotine dependence cessation was associated with reduced likelihood of several mental disorders and a higher quality of life compared to those with current nicotine dependence. These findings provide further support for public health policy aimed at smoking cessation.     

Comorbid bipolar disorder in Tourette's syndrome responds to the nicotinic receptor antagonist mecamylamine (Inversine).

BACKGROUND: We have previously proposed that the therapeutic effect of transdermal nicotine in Tourette's syndrome may involve nicotinic receptor inactivation resulting from a prolonged continuous exposure to nicotine. In vitro studies with nicotine and preliminary positive experience with mecamylamine (Inversine), a nicotinic receptor antagonist, in the clinical treatment of Tourette's syndrome patients, further supports the receptor inactivation hypothesis. METHODS: We retrospectively documented an unexpected therapeutic response to mecamylamine (2.5-7.5 mg/day) in two Tourette's syndrome patients who were subsequently found to have comorbid bipolar disorder as defined by DSM-IV criteria. RESULTS: In patient 1, the mood-stabilizing effect of mecamylamine was noticed by the patient during the course of mecamylamine treatment and brought to our attention, whereas for patient 2, manic symptoms were only apparent clinically following cessation of mecamylamine treatment. CONCLUSIONS: The clinical observations presented here suggest that nicotinic antagonists might be potential therapeutic agents for the treatment of bipolar disorder. Double-blind, placebo-controlled studies are now necessary to investigate these observations under more rigorous conditions.     

Nicotine dependence as comorbidity of alcohol dependence--epidemiology, etiology and therapy

There is a high association between alcohol and nicotine dependence. Compared to one particular dependence, associated nicotine and alcohol dependence are more severe and the course is more unfavourable for each dependence. This also applies to the sequels of dependence regarding physical health and cognitive functions. Possible biological causes for this high comorbidity are 1) an additive rewarding effect by combined consumption, 2) substance interaction with an impact on receptor activation and metabolism which results in reduction of adverse acute alcohol effects, and 3) a combined genetic disposition for both addictions. From a psychological point of view the association of both acts of use is learned. There is no evidence for the commonly presumed fundamental lack of interest, motivation, and ability for smoking cessation in alcohol dependent patients. The outcome of smoking cessation programs, however, is less successful compared to smokers without alcohol problems. Respective studies have used the common therapeutic strategies for nicotine addiction. Specifically adapted strategies for patients with a dual dependence are required.     

Sex differences in shoplifting: results from a national sample

ABSTRACT: This study presents the sex differences in sociodemographics and in psychiatric correlates of shoplifting in the United States. Data were drawn from the National Epidemiologic Survey on Alcohol and Related Conditions, a nationally representative sample of US adults. Shoplifting was associated with numerous psychiatric and addictive disorders with significant sex effects. Women with a lifetime history of shoplifting were significantly more likely than men with a lifetime history of shoplifting to have a lifetime diagnosis of alcohol abuse or dependence, nicotine dependence, cannabis, amphetamine, cocaine, or inhalant use disorder, and antisocial personality disorder, whereas men were significantly more likely than women to have a lifetime diagnosis of generalized anxiety disorder. The findings suggest that shoplifting could be better understood as a behavioral manifestation of a broader impaired impulse control spectrum in women. Shoplifting could be more a part of the externalizing spectrum disorders rather than the internalizing spectrum disorders in women compared to men.     

Neuroimaging, genetics and the treatment of nicotine addiction

Advances in neuroimaging and genomics provide an unprecedented opportunity to accelerate medication development for nicotine dependence and other addictions. Neuroimaging studies have begun to elucidate the functional neuroanatomy and neurochemistry underlying effects of nicotine and nicotine abstinence. In parallel, genetic studies, including both candidate gene and genome-wide association approaches, are identifying key neurobiological targets and pathways important in addiction to nicotine. To date, only a few neuroimaging studies have explored effects of nicotine or abstinence on brain activity as a function of genotype. Most analyses of genotype are retrospective, resulting in small sample sizes for testing effects of the minor alleles for candidate genes. The purpose of this review is to provide an outline of the work in neuroimaging, genetics, and nicotine dependence, and to explore the potential for increased integration of these approaches to improve nicotine dependence treatment.     

Lack of association between single nucleotide polymorphisms in the corticotropin releasing hormone receptor 1 (CRHR1) gene and alcohol dependence

While the physiological mechanisms that contribute to the development of alcohol dependence remain unclear, a number of recent studies have indicated a role for the corticotropin releasing hormone receptor 1 (CRHR 1) in modulating the response of the central nervous system to ethanol. Based on these data, the present study aims to identify associations between variations in the CRHR 1 gene and alcohol dependence in a population of individuals of European ancestry. In order to identify such putative associations, five single nucleotide polymorphisms (SNPs) in the CRHR 1 gene were analyzed in 120 alcohol dependent and 180 control subjects. In comparing both allele and genotype frequencies at these five loci between alcohol dependent and control populations, no significant associations between variations in the CRHR 1 gene and alcohol dependence were detected. The results of this study suggest that polymorphisms in the CRHR 1 gene are not major risk factors for the development of alcohol dependence in persons of European ancestry.     

Association of smoking and nicotine dependence with trauma and posttraumatic stress disorder in a general population sample

This study is aimed at investigating the association between trauma, posttraumatic stress disorder (PTSD), smoking, and nicotine dependence. Data were collected in a representative population sample of 4075 adults aged 18 to 64 with the Composite International Diagnostic Interview. Findings show increased odds ratios (ORs) for smoking (OR: 1.28; 95% CI: 1.09-1.51) and nicotine dependence (OR: 1.52; 95% CI: 1.26-1.82) in traumatized persons, independent of PTSD. Persons with PTSD tended to have higher odds for smoking (OR: 2.12; 95% CI: 1.16-3.90) and nicotine dependence (OR: 2.70; 95% CI: 1.57-4.65), but also had lower rates for quitting smoking (OR: 0.38; 95% CI: 0.17-0.84) and for remission from nicotine dependence (OR: 0.18; CI: 0.05-0.63). We conclude that persons suffering from PTSD might need comprehensive aid in smoking cessation.     

Negative affective states and cognitive impairments in nicotine dependence

Smokers have substantial individual differences in quit success in response to current treatments for nicotine dependence. This observation may suggest that different underlying motivations for continued tobacco use across individuals and nicotine cessation may require different treatments in different individuals. Although most animal models of nicotine dependence emphasize the positive reinforcing effects of nicotine as the major motivational force behind nicotine use, smokers generally report that other consequences of nicotine use, including the ability of nicotine to alleviate negative affective states or cognitive impairments, as reasons for continued smoking. These states could result from nicotine withdrawal, but also may be associated with premorbid differences in affective and/or cognitive function. Effects of nicotine on cognition and affect may alleviate these impairments regardless of their premorbid or postmorbid origin (e.g., before or after the development of nicotine dependence). The ability of nicotine to alleviate these symptoms would thus negatively reinforce behavior, and thus maintain subsequent nicotine use, contributing to the initiation of smoking, the progression to dependence and relapse during quit attempts. The human and animal studies reviewed here support the idea that self-medication for pre-morbid and withdrawal-induced impairments may be more important factors in nicotine addiction and relapse than has been previously appreciated in preclinical research into nicotine dependence. Given the diverse beneficial effects of nicotine under these conditions, individuals might smoke for quite different reasons. This review suggests that inter-individual differences in the diverse effects of nicotine associated with self-medication and negative reinforcement are an important consideration in studies attempting to understand the causes of nicotine addiction, as well as in the development of effective, individualized nicotine cessation treatments.