STin2 VNTR polymorphism is associated with comorbid tobacco use and mood disorders.

There is a significant comorbidity between mood disorders and tobacco use disorder (TUD), which may be related to both genetic and environmental factors. Gene variants of the 5-HT transporter, such as STin2 VNTR (a variable number of tandem repeats in the functional serotonin transporter intron 2) may be associated with mood disorders and TUD.

Zinc and zinc transporters in macrophages and their roles in efferocytosis in COPD

Our previous studies have shown that nutritional zinc restriction exacerbates airway inflammation accompanied by an increase in caspase-3 activation and an accumulation of apoptotic epithelial cells in the bronchioles of the mice. Normally, apoptotic cells are rapidly cleared by macrophage efferocytosis, limiting any secondary necrosis and inflammation. We therefore hypothesized that zinc deficiency is not only pro-apoptotic but also impairs macrophage efferocytosis. Impaired efferocytic clearance of apoptotic epithelial cells by alveolar macrophages occurs in chronic obstructive pulmonary disease (COPD), cigarette-smoking and other lung inflammatory diseases. We now show that zinc is a factor in impaired macrophage efferocytosis in COPD. Concentrations of zinc were significantly reduced in the supernatant of bronchoalveolar lavage fluid of patients with COPD who were current smokers, compared to healthy controls, smokers or COPD patients not actively smoking. Lavage zinc was positively correlated with AM efferocytosis and there was decreased efferocytosis in macrophages depleted of Zn in vitro by treatment with the membrane-permeable zinc chelator TPEN. Organ and cell Zn homeostasis are mediated by two families of membrane ZIP and ZnT proteins. Macrophages of mice null for ZIP1 had significantly lower intracellular zinc and efferocytosis capability, suggesting ZIP1 may play an important role. We investigated further using the human THP-1 derived macrophage cell line, with and without zinc chelation by TPEN to mimic zinc deficiency. There was no change in ZIP1 mRNA levels by TPEN but a significant 3-fold increase in expression of another influx transporter ZIP2, consistent with a role for ZIP2 in maintaining macrophage Zn levels. Both ZIP1 and ZIP2 proteins were localized to the plasma membrane and cytoplasm in normal human lung alveolar macrophages. We propose that zinc homeostasis in macrophages involves the coordinated action of ZIP1 and ZIP2 transporters responding differently to zinc deficiency signals and that these play important roles in macrophage efferocytosis.

N-acetylcysteine for therapy-resistant tobacco use disorder: a pilot study

Introduction N-Acetylcysteine (NAC) may have efficacy in treating tobacco use disorder (TUD) by reducing craving and smoking reward. This study examines whether treatment with NAC may have a clinical efficacy in the treatment of TUD. Methods A 12-week double blind randomized controlled trial was conducted to compare the clinical efficacy of NAC 3 g/day versus placebo. We recruited 34 outpatients with therapy resistant TUD concurrently treated with smoking-focused group behavioral therapy. Participants had assessments of daily cigarette use (primary outcome), exhaled carbon monoxide (COEXH) (secondary outcome), and quit rates as defined by COEXH<6 ppm. Depression was measured with the Hamilton Depression Rating Scale (HDRS). Data were analyzed using conventional and modified intention-to-treat endpoint analyses. Results NAC treatment significantly reduced the daily number of cigarettes used (Δ mean±SD = -10.9 ± 7.9 in the NAC-treated versus -3.2 ± 6.1 in the placebo group) and COEXH (Δ mean± SD = -10.4 ± 8.6 ppm in the NAC-treated versus -1.5 ± 4.5 ppm in the placebo group); 47.1% of those treated with NAC versus 21.4% of placebo-treated patients were able to quit smoking as defined by COEXH<6 ppm. NAC treatment significantly reduced the HDRS score in patients with tobacco use disorder. Conclusions These data show that treatment with NAC may have a clinical efficacy in TUD. NAC combined with appropriate psychotherapy appears to be an efficient treatment option for TUD.

Relationships Between Substance Use and Depressive Symptoms: A Longitudinal Study of Australian Adolescents

This study examined longitudinal relationships between depressive symptoms and use of alcohol, cigarettes, and illicit substances among adolescents, addressing methodological limitations and potential confounding in the extant literature. The sample comprised adolescents who were surveyed in Grades 6 (n = 916), 9 (n = 804), and 11 (n = 791). Cross-lagged path analyses were used to examine bi-directional relationships between substance use and depressive symptoms. Early adolescent depressive symptoms predicted mid-adolescent cigarette, alcohol, and illicit substance use (the latter among females only). Mid-adolescent depressive symptoms predicted late adolescent illicit substance use (females only). There were no statistically significant pathways from substance use to later depressive symptoms. However, these relationships were reduced to non-significance with the addition of covariates associated with the family environment, school, and individual. The findings suggest that the association between adolescent depressive symptoms and later substance use can be explained by common risk factors that produce vulnerability to both depression and substance use.

Short-term changes in quitting-related cognitions and behaviours after the implementation of plain packaging with larger health warnings : findings from a national cohort study with Australian adult smokers

ABSTRACT
Background: Plain packaging (PP) with larger graphic health warnings (GHWs) was implemented in Australia in late 2012. This study examined effects of these packaging changes on short-term changes in quitting-related cognitions and behaviours.
Methods: We used a series of cohorts of Australian adult cigarette smokers originally sourced from a nationally representative cross-sectional tracking survey, followed up approximately 1 month after their baseline interview (n(weighted)=5441). Logistic regression analyses compared changes in seven quitting-related outcomes over this 1-month follow-up period for the cohorts surveyed before PP, over the period of transition to PP, and during the first year of PP, adjusting for baseline levels of the outcome and covariates.
Results: Compared to the referent group of smokers who completed their follow-up survey pre-PP, those who were followed-up in the early transition period showed greater increases in rates of stopping themselves from smoking (OR=1.51, 95% CI (1.08 to 2.10)) and higher quit attempt rates (OR=1.43, 95% CI (1.00 to 2.03)), those followed-up in the late transition period showed greater increases in intentions to quit (OR=1.42, 95% CI (1.06 to 1.92)) and pack concealment (OR=1.55, 95% CI (1.05 to 2.31)), and those followed- up in the first year of PP showed higher levels of pack concealment (OR=1.65, 95% CI (1.01 to 2.72)), more premature stubbing out of cigarettes (OR=1.55, 95% CI (1.01 to 2.36)), and higher quit attempt rates (OR=1.52, 95% CI (1.01 to 2.30)).
Conclusions: These findings provide some of the strongest evidence to date that implementation of PP with larger GHWs was associated with increased rates of quitting cognitions, microindicators of concern and quit attempts among adult cigarette smokers.

Are quitting-related cognitions and behaviours predicted by proximal responses to plain packaging with larger health warnings? Findings from a national cohort study with Australian adult smokers

Background: Implementation of tobacco plain packaging (PP) with larger graphic health warnings (GHWs) in Australia had positive effects on responses reflecting the specific objectives of the PP policy and on follow-up quitting-related cognitions and behaviours. The aim of this study was to examine predictive relationships bewteen these proximal and distal outcomes.
Methods: A nationally representative sample of Australian adult cigarette smokers completed a baseline survey and a 1-month follow-up survey within the first year of policy implementation (n(weighted)=3215). Logistic regression analyses tested whether baseline measures of cigarette appeal, GHW effectiveness, perceived harm and concern/enjoyment predicted each of seven follow-up measures of quitted-related cognitions and behaviours, adjusting for baseline levels of the outcome and covariates.
Results: In multivariable models, we found consistent evidence that several baseline measures of GHW effectiveness positively and significantly predicted the likelihood that smokers at follow-up reported thinking about quitting at least daily, intending to quit, having a firm date to quit, stubbing out cigarettes prematurely, stopping oneself from smoking and having attempted to quit. Two of the quitting-related outcomes were also predicted by feeling more smoking-related concern than enjoyment. A smaller number of the appeal variables were prospectively associated with quitting-related outcomes, while believing that brands do not differ in harmlessness did not positively predict any outcomes.
Conclusions: These findings provide an initial insight into the pathways through which PP with larger GHWs may lead to changes in smoking behaviour. Future research should examine whether the effects are conditional on individual demographic and smoking characteristics.

Australian adult smokers' responses to plain packaging with larger graphic health warnings 1 year after implementation: results from a national cross-sectional tracking survey

Abstract
Background We assessed whether the Australian plain packs with larger graphic health warnings (GHWs) achieved three specific objectives of reducing the appeal of tobacco, increasing health warning effectiveness and reducing the ability of packaging to mislead about smoking harms.
Methods We compared responses from continuous cross-sectional telephone surveys of n=2176 cigarette smokers during pre-plain packaging (April–September 2012, pre-PP) with n=759 surveyed in the transition period (October–November 2012) and n=4240 during the first year of implementation (December 2012–November 2013, PP year 1), using multivariate logistic regression analyses.
Results From pre-PP to PP year 1, more smokers disliked their pack (p<0.001), perceived lower pack appeal (p<0.001), lower cigarette quality (p<0.001), lower satisfaction (p<0.001) and lower value (p<0.001) and disagreed brands differed in prestige (p=0.003). There was no change in perceived differences in taste of different brands. More smokers noticed GHWs (p<0.001), attributed much motivation to quit to GHWs (p<0.001), avoided specific GHWs when purchasing (p<0.001), and covered packs (p<0.001), with no change in perceived exaggeration of harms. PP year 1 saw an increased proportion believing that brands do not differ in harmfulness (p=0.004), but no change in the belief that variants do not differ in strength or the perceived harmfulness of cigarettes compared with a year ago. Interactions signified greater change for four outcomes assessing aspects of appeal among young adults and two appeal outcomes among mid-aged adults.
Conclusions The specific objectives of plain packaging were achieved and generally sustained among adult smokers up to 12 months after implementation.

Changes in use of types of tobacco products by pack sizes and price segments, prices paid and consumption following the introduction of plain packaging in Australia

Objectives: To describe changes among smokers in use of various types of tobacco products, reported prices paid and cigarette consumption following the standardisation of tobacco packaging in Australia.
Methods: National cross-sectional telephone surveys of adult smokers were conducted from April 2012 (6 months before transition to plain packaging (PP) to March 2014 (15 months afterwards). Multivariable logistics regression assessed changes in products, brands and pack types/sizes; multivariable linear regression examined changes in inflation-adjusted prices paid and reported cigarette consumption between the pre-PP and three subsequent periods – the transition phase, PP year 1 and PP post-tax (post a 12.5% tax increase in December 2013).
Results: The proposition of current smokers using roll-your-own (RYO) products fluctuated over the study period. Proportions using value brands of factory-made (FM) cigarettes increased from pre-PP (21.4%) to PP year 1 (25.5%; p=0.002) and PP post-tax (27.8%; p<0.001). Inflation-adjusted prices paid increased in the PP year 1 and PP post-tax phases; the largest increases were among premium FM brands, the smallest among value brands. Consumption did not change in PP year 1 among daily, regular or current smokers declined significantly in PP post-tax (mean=14.0, SE=0.33) compared to PP year 1 (mean=14.8, SE=0.17; p=0.037).
Conclusions: Introduction of PP was associated with an increase in use of value brands, likely due to increased numbers available and smaller increases in prices for value relative to premium brands. Reported consumption declined following the December 2013 tax increase.

Use of illicit tobacco following introduction of standardised packaging of tobacco products in Australia: results from a national cross-sectional survey

ABSTRACT
Objectives: To assess whether following standardisation of tobacco packaging in Australia, smokers were, as predicted by the tobacco industry, more likely to use illicit tobacco.
Methods: National cross-sectional telephone surveys conducted continuously from April 2012 (6 months before implementation of plain packaging (PP)) to March 2014 (15 months after) using responses from current cigarette smokers (n=8679). Changes between pre-PP, the transition to PP and PP phase were examined using logistic regression models.
Results: Among those whose factory-made cigarettes were purchased in Australia, compared with pre-PP, there were no significant increases in the PP phase in use of: ‘cheap whites’ (<0.1%; OR=0.24, 95% CI 0.04 to 1.56, p=0.134); international brands purchased for 20% or more below the recommended retail price (0.2%; OR=3.49, 95% CI 0.66 to 18.35, p=0.140); or packs purchased from informal sellers (<0.1%; OR=0.24, 95% CI 0.04 to 1.47, p=0.124). The prevalence of any use of unbranded illicit tobacco remained at about 3% (adjusted OR=0.79, 95% CI 0.58 to 1.08, p=0.141).
Conclusions: While unable to quantify the total extent of use of illicit manufactured cigarettes, in this large national survey we found no evidence in Australia of increased use of two categories of manufactured cigarettes likely to be contraband, no increase in purchase from informal sellers and no increased use of unbranded illicit ‘chop-chop’ tobacco.

Time series analysis of the impact of tobacco control policies on smoking prevalence among Australian adults, 2001–2011

Objective: To determine the impact of tobacco control policies and mass media campaigns on smoking prevalence in Australian adults.
Methods: Data for calculating the average monthly prevalence of smoking between January 2001 and June 2011 were obtained via structured interviews of randomly sampled adults aged 18 years or older from Australia’s five largest capital cities (monthly mean number of adults interviewed: 2375). The influence on smoking prevalence was estimated for increased tobacco taxes; strengthened smoke-free laws; increased monthly population exposure to televised tobacco control mass media campaigns and pharmaceutical company advertising for nicotine replacement therapy (NRT), using gross ratings points; monthly sales of NRT, bupropion and varenicline; and introduction of graphic health warnings on cigarette packs. Autoregressive integrated moving average (ARIMA) models were used to examine the influence of these interventions on smoking prevalence.
Findings: The mean smoking prevalence for the study period was 19.9% (standard deviation: 2.0%), with a drop from 23.6% (in January 2001) to 17.3% (in June 2011). The best-fitting model showed that stronger smoke-free laws, tobacco price increases and greater exposure to mass media campaigns independently explained 76% of the decrease in smoking prevalence from February 2002 to June 2011.
Conclusion: Increased tobacco taxation, more comprehensive smoke-free laws and increased investment in mass media campaigns played a substantial role in reducing smoking prevalence among Australian adults between 2001 and 2011.

The impact of maternal smoking during pregnancy on depressive and anxiety behaviors in children: the Norwegian Mother and Child Cohort Study.

BACKGROUND: Maternal smoking during pregnancy (MSDP) is associated with multiple adverse childhood outcomes including externalizing behaviors. However, the association between MSDP and internalizing (anxiety and depressive) behaviors in offspring has received less investigation. We aimed to assess the association between MSDP and childhood internalizing (anxiety and depressive) behaviors in a very large, well-characterized cohort study. METHODS: We assessed the association between MSDP and internalizing behaviors in offspring utilizing information drawn from 90,040 mother-child pairs enrolled in the Norwegian Mother and Child Cohort Study. Mothers reported smoking information, including status and frequency of smoking, twice during pregnancy. Mothers also reported their child's internalizing behaviors at 18 months, 36 months, and 5 years. Associations between MSDP and childhood internalizing behaviors, including dose-response and timing of smoking in pregnancy, were assessed at each time point. RESULTS: MSDP was associated with increased internalizing behaviors when offspring were aged 18 months (B = 0.11, P <0.001) and 36 months (B = 0.06, P <0.01), adjusting for numerous potential confounders. Higher rates of smoking (e.g., >20 cigarettes per day) were associated with higher levels of internalizing behaviors. Maternal smoking during early pregnancy appeared to be the critical period for exposure. CONCLUSIONS: We found evidence supporting a potential role for MSDP in increasing internalizing (anxiety and depressive) behaviors in offspring. We also found evidence supportive of a possible causal relationship, including dose-dependency and support for a predominant role of early pregnancy exposure. Further investigation utilizing genetically informed designs are warranted to assess this association.

Impact of cannabis use on long-term remission in bipolar I and schizoaffective disorder

OBJECTIVE: To investigate the impact of regular cannabis use on long-term remission of mood symptoms in bipolar spectrum disorders. METHODS: The 24-month prospective observational study included patients (n=239) with bipolar I disorder and schizoaffective disorder, bipolar type. Participants were classified as regular cannabis users (three times or more per week) or non-users. The primary outcome measure was the achievement of remission on the evaluations during the 24 months. RESULTS: Of the 234 participants for whom data was available, 25 (10.7%) were regular cannabis users, and the group comprised significantly more males than females. In the total population, cannabis use was significantly associated with decreased likelihood of remission during the 24-month follow-up period. Subgroup analyses showed that cannabis use was significantly associated with lower remission rates on the Hamilton Depression Rating Scale in females (n=139) and patients prescribed mood stabilizers alone (n=151), whereas in males (n=95) and patients prescribed olanzapine and/or a mood stabilizer (n=83), cannabis use was significantly associated with lower remission rates on the Young Mania Rating Scale. Remission rates were lowest in the concurrent cannabis and tobacco smoking group (n=22) followed by the tobacco smoking only group (n=97), and the non-smoker group (n=116). The post-hoc analysis revealed that all remission rates were significantly lower in the concurrent cannabis and the tobacco smoking group compared to the non-smoker group. CONCLUSION: Cannabis use negatively affects the long-term clinical outcome in patients with bipolar spectrum disorders. A comprehensive assessment and integrated management of cannabis use are required to achieve better treatment outcomes for bipolar spectrum disorders.

Developmental trajectories of adolescent cannabis use and their relationship to young adult social and behavioural adjustment: a longitudinal study of Australian youth

This study aimed to identify distinct developmental trajectories (sub-groups of individuals who showed similar longitudinal patterns) of cannabis use among Australian adolescents, and to examine associations between trajectory group membership and measures of social and behavioural adjustment in young adulthood. Participants (n=852, 53% female) were part of the International Youth Development Study. Latent class growth analysis was used to identify distinct trajectories of cannabis use frequency from average ages 12 to 19, across 6 waves of data. Logistic regression analyses and analyses of covariance were used to examine relationships between trajectory group membership and young adult (average age: 21) adjustment, controlling for a range of covariates. Three trajectories were identified: abstainers (62%), early onset users (11%), and late onset occasional users (27%). The early onset users showed a higher frequency of antisocial behaviour, violence, cannabis use, cannabis-related harms, cigarette use, and alcohol harms, compared to the abstinent group in young adulthood. The late onset occasional users reported a higher frequency of cannabis use, cannabis-related harms, illicit drug use, and alcohol harms, compared to the abstinent group in young adulthood. There were no differences between the trajectory groups on measures of employment, school completion, post-secondary education, income, depression/anxiety, or alcohol use problems. In conclusion, early onset of cannabis use, even at relatively low frequency during adolescence, is associated with poorer adjustment in young adulthood. Prevention and intervention efforts to delay or prevent uptake of cannabis use should be particularly focussed on early adolescence prior to age 12.

Effects of exercise on the desire to smoke and physiological responses to temporary smoking abstinence: a crossover trial

RATIONALE: Exercise has been shown to attenuate cigarette cravings during temporary smoking abstinence; however, the mechanisms of action are not clearly understood. OBJECTIVES: The objectives of the study were to compare the effects of three exercise intensities on desire to smoke and explore potential neurobiological mediators of desire to smoke. METHODS: Following overnight abstinence, 40 participants (25 males, 18-59 years) completed three 15 min sessions of light-, moderate-, or vigorous-intensity exercise on a cycle ergometer in a randomized crossover design. Ratings of desire to smoke were self-reported pre- and post-exercise and heart rate variability was measured throughout. Saliva and blood were analyzed for cortisol and noradrenaline in a sub-sample. RESULTS: Exercise influenced desire to smoke (F [2, 91] = 7.94, p < 0.01), with reductions greatest immediately after vigorous exercise. There were also significant time x exercise intensity interaction effects for heart rate variability and plasma noradrenaline (F [8, 72] = 2.23, p = 0.03), with a bias in noradrenaline occurring between light and vigorous conditions (adjusted mean difference [SE] = 2850 ng/ml [592], p < 0.01) at 5 min post-exercise. There was no interaction of time x exercise intensity for plasma and salivary cortisol levels. CONCLUSIONS: These findings support the use of vigorous exercise to reduce cigarette cravings, showing potential alterations in a noradrenergic marker.