Calcyon is a single transmembrane protein predominantly expressed in the brain. Very recently, calcyon has been implicated in clathrin mediated endocytosis, a critical component of synaptic plasticity. At the genetic level, preliminary evidence supports an association between attention-deficit/hyperactivity disorder (ADHD) and polymorphisms in the calcyon gene. As little is known about the potential role of calcyon in ADHD, animal models may provide important insights into this issue.
We examined calcyon mRNA expression in the frontal-striatal circuitry of three-, five-, and ten-week-old Spontaneously Hypertensive Rats (SHR), the most commonly used animal model of ADHD, and Wistar-Kyoto (WKY; the strain from which SHR were derived). As a complement, we performed a co-expression network analysis using a database of mRNA gene expression profiles of multiple brain regions in order to explore potential functional links of calcyon to other genes.
In all age groups, SHR expressed significantly more calcyon mRNA in the medial prefrontal and orbital frontal cortices than WKY rats. In contrast, in the motor cortex, dorsal striatum and nucleus accumbens, calcyon mRNA expression was only significantly elevated in SHR in younger animals. In both strains, calcyon mRNA levels decreased significantly with age in all regions studied. In the co-expression network analysis, we found a cluster of genes (many of them poorly studied so far) strongly connected to calcyon, which may help elucidate its role in the brain. The pair-wise relations of calcyon with other genes support its involvement in clathrin mediated endocytosis and, potentially, some other membrane/vesicular processes. Interestingly, no link was found between calcyon and the dopamine D1 receptor, which was previously shown to interact with the C-terminal of calcyon.
The results indicate an alteration in calcyon expression within the frontal-striatal circuitry of SHR, especially in areas involved in cognitive processes. These findings extend our understanding of the molecular alterations in SHR, a heuristically useful model of ADHD.
Calcyon is a single transmembrane endocytic protein that regulates clathrin assembly and clathrin mediated endocytosis in brain. Ultrastructural studies indicate that calcyon localizes to spines, but whether it regulates glutamate neurotransmission is not known. Here, we show that deletion of the calcyon gene in mice inhibits agonist stimulated endocytosis of AMPA receptors, without altering basal surface levels of the GluR1 or GluR2 subunits. Whole cell patch clamp studies of hippocampal neurons in culture and CA1 synapses in slices revealed that knockout of calcyon abolishes long term synaptic depression (LTD) whereas mini-analysis in slices indicated basal transmission in hippocampus is unaffected by the deletion. Further, transfection of GFP-tagged calcyon rescued the ability of knockout cultures to undergo LTD. In contrast, intracellular dialysis of a fusion protein containing the clathrin light chain binding domain of calcyon blocked the induction of LTD in wild type hippocampal slices. Taken together, the present studies involving biochemical, immunological and electrophysiological analyses raise the possibility that calcyon plays a specialized role in regulating activity-dependent removal of synaptic AMPA receptors.
synaptic plasticity; glutamate transmission; clathrin mediated endocytosis; ADHD; schizophrenia
Gene linkage and association studies have implicated the region of chromosome 10q containing the calcyon locus with attention deficit hyperactivity disorder (ADHD), bipolar disorder, and schizophrenia susceptibility. In addition, levels of calcyon protein and transcripts are also significantly increased in postmortem tissue from schizophrenic brains. But whether altered calcyon expression might be part of the disease etiology or merely a patho-physiological side effect is not known. To begin to address this issue, we generated a transgenic mouse line (CalOE) using the human calcyon cDNA in which calcyon expression is up-regulated in a number of forebrain structures including the hippocampus, prefrontal cortex, striatum, and amygdala. Compared to control littermates, the CalOE mice display a range of abnormal behaviors including spontaneous hyperactivity, reduced anxiety, and/or impaired restraint (harm avoidance) that would indicate that calcyon up-regulation leads to deficits in control over behavioral output.
ADHD; schizophrenia; disease model; anxiety; impulsivity; novelty seeking
Calcyon is a neural enriched, single transmembrane protein that interacts with clathrin light chain (CLC) and stimulates clathrin assembly and clathrin mediated endocytosis (CME). A similar property is shared by the heterotetrameric adaptor protein (AP) complexes AP-1, AP-2, and AP-3 which recruit cargoes for insertion into clathrin coated transport vesicles. Here we report that AP medium (µ) subunits interact with a YXXØ-type tyrosine motif located at residues 133–136 in the cytoplasmic domain of calcyon. Site specific mutagenesis of the critical tyrosine and bulky hydrophobic residues tyrosine 133 and methionine 136 preferentially abrogated binding of the ubiquitous and neuronal isoforms of µ3, and also impacted µ1 and µ2 binding but to a lesser degree. The relevance of these interactions was explored in vivo using mice harboring null-alleles of calcyon. As seen in the mutagenesis studies, calcyon deletion in mice preferentially altered the subcellular distribution of AP-3 suggesting that calcyon could regulate membrane-bound pools of AP-3 and AP-3 function. To test this hypothesis, we focused on the hilar region of hippocampus, where levels of calcyon, AP-3, and AP-3 cargoes are abundant. We analyzed brain cryosections from control and calcyon null mice for zinc transporter 3 (ZnT3), and phosphatidylinositol-4-kinase type II alpha (PI4KIIα), two well-defined AP-3 cargoes. Confocal microscopy indicated that ZnT3 and PI4KIIα are significantly reduced in the hippocampal mossy fibers of calcyon knock-out brain, a phenotype previously described in AP-3 deficiencies. Altogether, our data suggest that calcyon directly interacts with µ3A and µ3B, and regulates the subcellular distribution of AP-3 and the targeting of AP-3 cargoes.
Synthetic glucocorticoids such as dexamethasone (DEX) are commonly used to promote fetal lung maturation in at-risk preterm births, but there is emerging evidence of subsequent neurobehavioral abnormalities in these children e.g. problems with inattention/hyperactivity. However, molecular pathways mediating effects of glucocorticoid overexposure on motor and cognitive development are poorly understood.
In this study with common marmoset monkeys, we investigated for neonatal and adulthood effects of antenatal DEX treatment on the expression of the corticosteroid receptors and also calcyon, a risk gene for attention-deficit/hyperactivity disorder, in the prefrontal cortex (PFC). Pregnant marmosets were exposed to DEX (5 mg/kg body weight) or vehicle during early (days 42-48) or late (days 90-96) stages of the 144-day pregnancy.
In neonates, relative to controls, glucocorticoid receptor (GR) mRNA levels were significantly reduced after the late DEX treatment in the medial, orbital and dorsal PFC and after the early DEX treatment in the dorsal PFC. The early DEX exposure, specifically, resulted in significant reduction in calcyon mRNA expression in the medial, orbital, dorsal and lateral PFC relative to controls. Mineralocorticoid receptor (MR) mRNA levels were not significantly affected by DEX treatment. In adults, PFC GR, calcyon, and MR mRNA levels were not significantly affected by early or late prenatal DEX treatment.
These findings indicate that antenatal DEX treatment could lead to short-term alterations in PFC expression of the GR and calcyon genes, with possible neurodevelopmental functional consequences.
Smoking prevention interventions have been shown to be effective in reducing smoking prevalence in the United States. Further work is needed to address smoking in China, where over one third of the world’s current smokers reside. China, with more than 60% of the male population being smokers, also presents a unique opportunity to test cognitive processes involved in depression, social influences, and smoking. Adolescents at-risk for developing depression may process social information differently from low-risk counterparts.
The Wuhan Smoking Prevention Trial was a school-based longitudinal randomized controlled trial aimed at preventing initiation and escalation of adolescent smoking behaviors. Thousand three hundred and ninety-one male seventh-grade students were assessed with a 200-item paper-and-pencil baseline survey, and it was readministered 1 year later following program implementation.
Friend prevalence estimates were significantly higher among 30-day smokers and among those at highest risk for depression symptoms. The program appeared to be successful in changing the perception of friend smoking prevalence only among adolescents with a comorbidity of high scores of depression symptoms and who have experimented previously with smoking. This Program × Comorbidity interaction on perceived friend smoking prevalence was significant in predicting 30-day smoking 1 year after program implementation.
This study provides evidence that those adolescents with high levels of depressive symptoms may be more sensitive to social influences associated with smoking prevalence. Individual Disposition × Social Environmental Influences may be important when developing future effective prevention programming.
The authors tested 2 mechanisms for the relation of movie smoking exposure with onset of cigarette smoking in adolescence. Longitudinal data with 8-month follow-up were obtained from a representative sample of 6,522 U.S. adolescents, ages 10–14 years. Structural modeling analysis based on initial nonsmokers, which controlled for 10 covariates associated with movie exposure, showed that viewing more smoking in movies was related to increases in positive expectancies about smoking and increases in affiliation with smoking peers, and these variables were both related to smoking onset. A direct effect of movie exposure on smoking onset was also noted. Mediation findings were replicated across cross-sectional and longitudinal analyses. Tests for gender differences indicated that girls showed larger effects of movie exposure for some variables. Implications for policy and prevention research are discussed.
smoking; adolescents; movies; expectancies; peers
Attitudes and policy towards smoking changed over the past years in many countries including the Netherlands. Generally, this led to a decrease in smoking prevalence. As demonstrated in twin and family studies, individual differences in smoking behavior are partly influenced by genetic factors. We explore whether the current change in environmental conditions has influenced the genetic architecture of smoking. This would constitute evidence for Gene × Environment (G×E) interaction.
Data on smoking were available from 2 cohorts of young adult twins (18-25 year) registered with the Netherlands Twin Register. The first cohort completed a survey in 1993-1995 (n = 2669) and the second in 2009-2010 (n = 2339). Prevalence and genetic architecture of smoking were compared across cohorts using structural equation models in MX.
Smoking prevalence decreased from 40-51% to 22-23% between 1993-1995 and 2009-2010. Genetic analyses, making use of the different genetic resemblance in monozygotic and dizygotic twins, showed that the heritability was the same in both cohorts.
The change in policy and smoking attitudes that led to a decrease in prevalence of smoking did not change the heritability of smoking and thus no evidence was found for GxE interaction.
Ocular and childhood myasthenia gravis (MG) cases seem relatively more common in Oriental than in Caucasian populations, but there have been no comprehensive serological studies on patients from mainland China.
391 unselected patients with MG attending Tongji Hospital in WuHan (the largest hospital in the province of HuBei, China) were studied during a 15‐month period; most had already received treatment for their condition.
The male to female ratio was 0.8. 50% of the patients were children (<15 years), and age at onset showed a single peak at between 5 and 10 years of age. 64% of the children and 66% of the adults were positive for acetylcholine receptor (AChR) antibodies but the antibody titres were lower than in similar Caucasian studies, although this was partly due to the high incidence of ocular MG. Of the 43 patients with generalised MG without AChR antibodies, only 1 had muscle‐specific kinase antibodies (2.5%) and 2 had voltage‐gated calcium channel antibodies indicating probable Lambert–Eaton myasthenic syndrome. 75% of the children, compared with only 28% of the adults, had ocular MG. Thymoma was evident by MRI in 1.5% of children and in 20% of adults. Despite most patients having received prednisone, very few had obtained full clinical remission.
This study emphasises the frequency of early childhood onset with ocular symptoms and shows that many of these patients have AChR antibodies. By contrast, patients presenting in later age seem to be very uncommon in comparison with recent studies in Caucasian populations.
Cigarette smoking behavior may be influenced by catechol-O-methlyltransferase (COMT), dopamine beta-hydroxylase (DBH), and monamine oxidase-A (MAO-A), genes that play roles in dopamine metabolism. The association between common polymorphisms of these genes and smoking behavior was assessed among 10,059 Caucasian volunteers in Washington County, MD in 1989.
Age-adjusted logistic regression was used to measure the association between variants of these single nucleotide polymorphisms and smoking initiation and persistent smoking.
Overall, no association was seen between each genotype and smoking behavior. However, among younger (<54 years) women, the COMT GG genotype was positively associated with smoking initiation (OR=1.3; 95% CI: 1.1, 1.5), and the MAO-A TT genotype was inversely associated with persistent smoking (OR=0.5; 95% CI: 0.3, 0.9). Men who smoked fewer than 10 cigarettes per day were more likely to be persistent smokers if they had the COMT GG (OR=1.7; 95% CI: 1.0, 2.9) or the DBH GG (OR=1.6; 95% CI: 1.0, 2.6) genotypes.
Overall the results of this large community-based study do not provide evidence to support the presence of important associations between variants of COMT, DBH, or MAO-A and smoking initiation or persistent smoking.
tobacco; cigarette smoking; COMT; DBH; MAO-A
Background: Smoking among adolescents remains unacceptably high and the difference in potential risk factors for smoking initiation between male and female adolescents has been explored. Although the association between smoking initiation and dieting behaviour has been observed among girls, the mechanism of the association is unknown.
Objective: To examine prospectively the association between perceived importance of being thin at baseline and smoking initiation among girls.
Design: A four year prospective cohort survey including perceived importance of being thin at baseline and smoking behaviour, conducted in 1993 and 1996.
Setting and participants: 273 Massachusetts female adolescents aged 12–15 years at baseline who reported having smoked no more than one cigarette by the time of the baseline survey, drawn from households sampled by random digit dialling.
Main outcome measure: Progression to established smoking, defined as having smoked 100 or more cigarettes in their lifetime.
Results: After adjusting for age, smoking status at baseline, and race/ethnicity, girls who valued thinness most strongly and somewhat strongly were both more likely to have become established smokers, compared to the girls who valued thinness least strongly. The odds ratios are 4.5 (95% confidence interval (CI), 1.4 to 16.7) and 3.4 (95% CI 1.04 to 10.9), respectively.
Conclusions: The level of perceived importance of being thin among young female adolescents predicts future smoking initiation. Smoking prevention programmes designed for female adolescents may therefore benefit from the inclusion of content related to importance of being thin.
Using data from the National Longitudinal Study of Adolescent Health, this study examined the associations among family bonding factors and the initiation of smoking by race/ethnicity and age group among nonsmokers at Wave 1. Overall, 18% of the sample initiated smoking by Wave 2. For younger African American and Hispanic youth, high maternal satisfaction with the relationship was significantly protective of smoking initiation. For older Hispanics, high parental presence and high parent-family connectedness were protective against smoking initiation while lack of awareness about the adolescent’s whereabouts was a risk factor for initiation in both younger and older Caucasians, and in the older Hispanics. Our results underscore the importance of maintaining high levels of family bonding with the adolescent throughout early and late adolescence in order to decrease tobacco initiation.
Adolescence; Smoking initiation; Parental influence; Ethnicity; Race
Extant twin research on the depression–smoking association in adolescents has been conducted in U.S. and European samples and considered depression as a unitary phenotype. This study explored genetic and environmental influences on covariation between smoking initiation and 4 depressive symptom dimensions (positive affect [PA], negative affect [NA], somatic features [SF], and interpersonal problems [IP]) in adolescent Chinese twins.
Questionnaires measuring current depressive symptoms and lifetime smoking initiation were administered to 602 twin pairs (M [SD] age = 12.2 (1.93) years, range 9–16 years). Cholesky bivariate decomposition models examined influences on each depressive symptom dimension, smoking initiation, and their covariation using age- and sex-adjusted threshold variables.
Within-twin correlations between smoking initiation and each depressive symptom dimension were significant (|r|s = .29–.61). Bivariate twin modeling showed significant genetic effects on overall depressive symptoms (55% variance), shared environment effects on NA (36%) and PA (53%), and shared environment effects on smoking initiation (46%) unique from PA. No other familial influences on the individual phenotypes (apart from those accounting for smoking–depression covariance) were significant. Relations of smoking initiation to overall depressive symptoms and IP were influenced by familial (shared environment and/or genetic) factors and nonshared environmental factors. The SF–smoking initiation relation was influenced mostly by familial factors. Only shared environment significantly influenced the association of lower PA and higher NA to smoking initiation.
Relations between each symptom dimension and smoking initiation are of sizeable magnitude in Chinese adolescents. Genetic and environmental factors underlying depression–smoking comorbidity may vary across different depressive symptom dimensions.
A better understanding of the genetic determinants of tobacco smoking might help in developing more effective cessation therapies, tailored to smokers' genotype. Insertion/deletion polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) has been linked to vulnerability to smoking and ability to quit. We aimed to determine whether 5-HTTLPR genotype is associated with smoking behavior in Caucasians from Northern Poland and to investigate other risk factors for tobacco smoking.
5-HTTLPR genotypes were determined in 149 ever smokers (66 females; mean age 53.0 years) and 158 gender and ethnicity matched never smoking controls (79 females; mean age 45.0 years) to evaluate the association of this polymorphism with ever smoking status. Analysis of smokers was performed to evaluate the role of 5-HTTLPR in the age of starting regular smoking, the number of cigarettes smoked daily, pack-years, FTND score, duration of smoking, and the mean length of the longest abstinence on quitting. Genotype was classified according to the presence or absence of the short (S) allele vs. the long (L) allele of 5-HTTLPR (i.e., S/S + S/L vs. L/L). Logistic regression analysis was also used to evaluate correlation between ever smoking and several selected variables.
We found no significant differences in the rates of S allele carriers in ever smokers and never smokers, and no relationship was observed between any quantitative measures of smoking and the polymorphism. Multivariate analysis demonstrated significant association between the older age (OR = 4.03; 95% CI: 2.33–6.99) and alcohol dependence (OR = 10.23; 95% CI: 2.09–50.18) and smoking.
5-HTTLPR seems to be not a major factor determining cigarette smoking in Poles. Probably, the risk of smoking results from a large number of genes, each contributing a small part of the overall risk, while numerous non-genetic factors might strongly influence these genetic undergrounds of susceptibility to smoking.
The authors investigated the association between exposure to smoking in movies and the initiation and progression of adolescent smoking over time among 6,522 U.S. adolescents (between the ages of 10 and 14 years, at baseline) in a nationally representative, 4-wave random-digit-dial telephone survey. They conducted a hazard (survival) analysis testing whether exposure to movie smoking and demographic, personality, social, and structural factors predict (a) earlier smoking onset and (b) faster transition to experimental (1–99 cigarettes/lifetime) and established smoking (>100 cigarettes/lifetime). Results suggest that higher exposure to movie smoking is associated with less time to trying cigarettes for the first time (adjusted hazard ratio = 1.66; 95% CI [1.37, 2.01]) but not with faster escalation of smoking behavior following initiation (adjusted hazard ratio = 1.53; 95% CI [0.84, 2.79]). In contrast, age, peer smoking, parenting style, and availability of cigarettes in the home were predictors of earlier onset and faster transition to established smoking. Thus, the authors concluded that the effect of exposure to mass-mediated images of smoking in movies may decline once adolescents have started to smoke, whereas peers and access to tobacco remain influential.
To understand how factors at multiple levels of influence impact adolescent smoking initiation.
Data from the Minnesota Adolescent Community Cohort, a population-based cohort, were analyzed. Adolescents were recruited from randomly selected geopolitical units (GPUs) in Minnesota at ages 12 to 13 (n=1,953), and were surveyed every six months (2000–2006) until 18. The association between baseline social factors and smoking initiation was analyzed using logistic regression. Linear regression was used to analyze predictors and age of initiation among smokers (n=603).
Higher proportion of 15–16 year-olds who smoke at the area-level (GPU) was associated with younger initiation (15.47 vs 15.87, p<.05). Higher proportion of the population employed and higher median household income were associated with older initiation (15.90 vs. 15.56 p<.05). Parent education, living with parents or siblings who smoke, living in homes that allow smoking, and having friends who smoke at baseline were associated with smoking initiation or younger initiation (p<.05). Participants whose parents had less than a high school education were 1.6 times more likely than those with college educated parents to have smoked more than a whole cigarette (CI=1.06, 2.26).
Factors at multiple levels of influence affect adolescent smoking initiation. Smoking by older age peers and lower SES predicts earlier smoking.
Adolescence is an important period of risk for the development of lifelong smoking behaviors. Compelling, although inconsistent, evidence suggests a relation between parental smoking and the risk of smoking initiation during adolescence. This study investigates unresolved issues concerning the strength and nature of the association between parent smoking and offspring smoking initiation.
We enrolled 564 adolescents aged 12-17, along with one of their parents, into the New England Family Study between 2001-2004. Lifetime smoking histories were obtained from parents and their adolescent offspring. Discrete-time survival analysis was used to investigate the influence of parental smoking histories on the risk of adolescent smoking initiation.
Parental smoking was associated with a significantly higher risk of smoking initiation in adolescent offspring (odds ratio=2.81, 95% CI=1.78, 4.41). In addition, the likelihood of offspring smoking initiation increased with the number of smoking parents and the duration of exposure to parental smoking, suggesting a dose-response relation between parental smoking and offspring smoking. Offspring of parents who had quit smoking were no more likely to smoke than offspring of parents who had never smoked. The effects of parental smoking on offspring initiation differed by sex (with a stronger effect of father's smoking on boys than girls), developmental period (with a stronger effect of parental smoking before the adolescent was age 13 than afterwards), and residence of parents (with effects of father's smoking being dependent on living in the same household as the adolescent). Parental smoking was also associated with stronger negative reactions to adolescents' first cigarette, a potential marker of the risk of progression to higher levels of use.
Parental smoking is an important source of vulnerability to smoking initiation among adolescents, and parental smoking cessation might attenuate this vulnerability.
Smoking; adolescents; parent-offspring transmission
This study examined the development of positive smoking expectancies and smoking behavior in an urban cohort of girls followed annually over ages 11-14. Longitudinal data from the oldest cohort of the Pittsburgh Girls Study (N=566, 56% African American, 44% Caucasian) were used to estimate a parallel process growth model of positive smoking expectancies and smoking behavior. Average level of positive smoking expectancies was relatively stable over ages 11-14, although there was significant variability in initial level and rate of change in positive smoking expectancies. Ethnicity was associated with expectancy intercept and slope, such that African American, relative to Caucasian, girls initially had more positive expectancies, and less rapid change in positive expectancies. Ethnic differences in past year smoking prevalence emerged at age 14, with greater smoking prevalence among Caucasian (17%), compared to African American (8%), girls. Initial level of positive smoking expectancies and initial smoking behavior were positively associated, but positive expectancies did not predict growth in smoking behavior. Depression at age 11 was concurrently and positively associated with both positive expectancies and smoking. Study results suggest the potential utility of culturally tailored smoking prevention efforts, and the potential secondary benefit of depression treatment to prevent smoking among at-risk girls.
cigarette smoking; positive smoking expectancies; adolescent girls; ethnicity
OBJECTIVE—To determine the extent to which Chinese American and white minors differ in age of smoking initiation, and to determine the effect of acculturation on smoking initiation.
DESIGN—Cross-sectional telephone surveys.
SETTING—Stratified random samples of the state of California, United States.
SUBJECTS—347 Chinese American and 10 129 white adolescents aged 12 through 17 years, from the California Tobacco Survey (1990-93) and the California Youth Tobacco Survey (1994-96).
OUTCOME MEASURES—Hazards (risk) of smoking initiation by age, smoking initiation rate, cumulative smoking rate, mean age of smoking initiation, and acculturation status.
STATISTICAL METHODS—Life table methods, proportional hazards models, and χ2 tests.
RESULTS—The risk of smoking initiation by age among Chinese American minors was about a third of that among white minors. The risk for Chinese Americans continued to rise even in later adolescence, in contrast to that for whites, which slowed after 15 years of age. Acculturation was associated significantly with smoking onset among Chinese Americans. Acculturation, smoking among social network members, attitudes toward smoking, and perceived benefits of smoking were associated with the difference in hazards of smoking onset between Chinese American minors and their white counterparts.
CONCLUSIONS—Chinese American adolescents had a lower level and a different pattern of smoking onset than white adolescents. Levels of acculturation and other known risk factors were associated with the hazards of smoking initiation among Chinese American minors and with the difference in smoking initiation between the Chinese and white adolescents. Tobacco prevention policies, strategies, and programmes for ethnically diverse populations should take acculturation factors into account.
Keywords: acculturation; Chinese Americans; smoking initiation; adolescence
Cigarette smoking and coal burning are the primary sources of indoor air pollution in Chinese households. However, effects of these exposures on Chinese children's respiratory health are not well characterized.
Seventh grade students (N = 5051) from 22 randomly selected schools in the greater metropolitan area of Wuhan, China, completed an in-class self-administered questionnaire on their respiratory health and home environment.
Coal burning for cooking and/or heating increased odds of wheezing with colds [odds ratio (OR) = 1.57, 95% confidence interval (CI): 1.07–2.29] and without colds (OR = 1.44, 95% CI: 1.05–1.97). For smoking in the home, the strongest associations were seen for cough (OR = 1.74, 95% CI: 1.17–2.60) and phlegm production (OR = 2.25, 95% CI: 1.36–3.72) without colds among children who lived with two or more smokers.
Chinese children living with smokers or in coal-burning homes are at increased risk for respiratory impairment. While economic development in China may decrease coal burning by providing cleaner fuels for household energy use, the increasing prevalence of cigarette smoking is a growing public health concern due to its effects on children. Adverse effects of tobacco smoke exposure were seen despite the low rates of maternal smoking (3.6%) in this population.
The α7 neuronal nicotinic acetylcholine receptor subunit gene (CHRNA7) is localized in a chromosomal region (15q14) linked to schizophrenia in multiple independent studies. CHRNA7 was selected as the best candidate gene in the region for a well-documented endophenotype of schizophrenia, the P50 sensory processing deficit, by genetic linkage and biochemical studies.
Subjects included Caucasian-Non Hispanic and African-American case-control subjects collected in Denver, and schizophrenic subjects from families in the NIMH Genetics Initiative on Schizophrenia. Thirty-five single nucleotide polymorphisms (SNPs) in the 5′-upstream regulatory region of CHRNA7 were genotyped for association with schizophrenia, and for smoking in schizophrenia.
The rs3087454 SNP, located at position −1831 bp in the upstream regulatory region of CHRNA7, was significantly associated with schizophrenia in the case-control samples after multiple-testing correction (P = 0.0009, African American; P = 0.013, Caucasian-Non Hispanic); the association was supported in family members. There was nominal association of this SNP with smoking in schizophrenia.
The data support association of regulatory region polymorphisms in the CHRNA7 gene with schizophrenia.
Nicotinic receptor; Schizophrenia; Polymorphism; Association; Sensory Processing; Alpha 7 nicotinic receptor; Regulatory region; Promoter
Exposure to smoking in movies is strongly associated with smoking uptake and maintenance among adolescents. However, little is known about what features of movies (e.g., the context for smoking or motives for a character smoking) moderate the association between exposure to movie smoking and adolescent smoking. This laboratory study examined whether exposure to movie smoking that is portrayed as having a clear motive is associated with the desire to smoke differently than smoking that is portrayed as having no clear motive.
A sample of 77 middle school students (mean age of 12.8 years, 62% male, 60% Caucasian) viewed movie clips that portrayed smoking as helping to facilitate social interaction, to relax, to appear rebellious, or as having no clear motive. After exposure to each clip, participants rated their desire to smoke.
Exposure to clips where smoking was portrayed as helping characters to relax was associated with a significantly stronger desire to smoke compared with clips where the motive for smoking was unclear. Desire to smoke was similar for clips where no motive was clear, social smoking clips, and rebellious smoking clips.
These results suggest that the way that smoking is portrayed in movies is important in determining its effect on adolescent smoking.
Although environmental smoking (i.e., paternal and maternal smoking, sibling smoking, and peer smoking) is one of the most important factors for explaining adolescent smoking behavior, not all adolescents are similarly affected. The extent to which individuals are vulnerable to smoking in their environment might depend on genetic factors. The aim of this study was to examine the interplay between environmental smoking and genes encoding components of the dopaminergic system (i.e., dopamine receptor D2, D4, and dopamine transporter DAT1) in adolescent smoking onset. Data from two longitudinal studies were used. Study 1 consisted of 991 non-smoking early adolescents (mean age = 12.52, SD = .57) whereas study 2 consisted of 365 non-smoking middle to late adolescents (mean age = 14.16, SD = 1.07) who were followed for 16 and 48 months, respectively. Logistic regression analyses were conducted using Mplus. In study 1, we found positive associations between parents' and friends' smoking at the first measurement and smoking status 16 months later. In study 2 we found a positive association between friends' smoking and smoking onset 48 months later. Neither study demonstrated any interaction effects of the DRD2, DRD4, or DAT1 genotypes. In conclusion, the effects of environmental smoking on smoking onset are similar for adolescent carriers and non-carriers of these specific genes related to the dopaminergic system.
Previous studies suggest that earlier cigarette smoking initiation in adolescence predicts greater cigarette consumption later in adolescence or adulthood. Results from these studies have been used to inform interventions for adolescent smoking. However, previous studies suffer from several important methodological limitations. The objective of the present study was to address these limitations by longitudinally and prospectively examining whether and how age of initiation of smoking among adolescents predicts cigarette consumption by age 16 or 17. Participants completed an in-class survey every 6 months for 2–3 school years. Participants included 395 adolescents (Mean age = 14 years at baseline; 53.2% female) from two public high schools in Northern California (Schools A and B) who completed self-report measures of smoking initiation, number of friends who smoke, and number of whole cigarettes smoked by the final survey time point. Adolescents who were older when they first smoked one whole cigarette were 5.3 to 14.6 times more likely in School A and 2.9 to 4.3 times more likely in School B to have smoked a greater number of cigarettes by age 16 or 17. Results suggested that earlier smoking initiation may not lead to heavier cigarette consumption later in time, as has been previously shown. There may be a period of heightened vulnerability in mid- or late adolescence where smoking experimentation is more likely to lead to greater cigarette consumption. Targeting prevention efforts to adolescents aged 14 to 17 years may further reduce smoking initiation among youth, thus limiting subsequent smoking-related morbidity and mortality in adulthood.
Adolescents; Cigarettes; Smoking initiation; Longitudinal
This study examined the associations between smoking initiation and, hostility, depressive symptoms, and bullying (bullies and bully-victims) among a culturally diverse sample of 1771 adolescents who reported never having smoked at baseline.
Data were from a longitudinal school-based experimental trial of smoking prevention programs in Southern California. Students were surveyed annually while in the 6th, 7th, and 8th grades. All students in the 24 participating schools were invited to participate in the study during the 6th grade.
The risk of smoking initiation was significantly higher among students who score higher on hostility and depressive symptoms, and were bully-victims.
The findings suggest that tobacco prevention programs should include strategies of managing hostile feelings and negative affect as part of the curriculum. In addition, it may be helpful to identify youth who score high on these psychosocial factors and teach them skills to handle interpersonal conflict and negative feelings to prevent their involvement in substance use.
adolescents; smoking initiation; hostility; depressive symptoms; and bullying