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1.  Association of the DRD2 gene Taq1A polymorphism and smoking behavior: A meta-analysis and new data 
Nicotine & Tobacco Research  2009;11(1):64-76.
Introduction:
Many studies have investigated the association of the dopamine type-2 receptor (DRD2) Taq1A polymorphism with tobacco use and cigarette smoking behaviors, but findings remain equivocal. There is a biological basis for considering that this association differs by sex, and differences in subpopulations might explain some of the contradictory evidence.
Methods:
Our a priori hypothesis was that the association of the DRD2 Taq1A polymorphism with smoking behavior would be more prominent in females than males. We therefore investigated the strength of evidence for an association between the DRD2 Taq1A polymorphism and smoking behavior in a large sample of females and used meta-analytic techniques to synthesize existing published data and explore the role of sex in explaining any heterogeneity between studies.
Results:
We did not observe any strong evidence of association between the DRD2 Taq1A polymorphism and smoking behavior, including smoking initiation, smoking persistence, and smoking rate, either in our female sample or in our meta-analysis of 29 studies, comprising 28 published studies and the data from the present study. Metaregression suggested an association between the proportion of male participants in a study and the individual study effect size, indicating a larger effect size with a greater proportion of male participants for smoking initiation and smoking persistence. This effect did not appear to be due to the inclusion of the data from the present study.
Discussion:
Available evidence does not support an association between the DRD2 Taq1A polymorphism and smoking behavior. Contrary to our a priori hypothesis, we found evidence of a stronger association in males than in females.
doi:10.1093/ntr/ntn012
PMCID: PMC3203402  PMID: 19246443
2.  CHRNA3 rs1051730 Genotype and Short-Term Smoking Cessation 
Nicotine & Tobacco Research  2011;13(10):982-988.
Introduction:
The rs1051730 genetic variant within the CHRNA5-A3-B4 gene cluster is associated with heaviness of smoking and has recently been reported to be associated with likelihood of stopping smoking. We investigated the potential association of rs1051730 genotype with reduced likelihood of smoking cessation in 2 cohorts of treatment-seeking smokers in primary care in the United Kingdom.
Methods:
Data were drawn from 2 clinical trials on which DNA was available. One sample was a randomized placebo-controlled trial of nicotine transdermal patch and the other sample an open-label trial where all participants received nicotine transdermal patch. Smoking status was biochemically verified. Logistic regression was used to assess evidence for association in each sample, and data were combined within a meta-analysis.
Results:
There was evidence of association of rs1051730 genotype with short-term (4-week) cessation in our open-label trial sample but not our placebo-controlled trial sample. When combined in a meta-analysis, this effect remained. There was no evidence of association at later follow-up intervals. Adjustment for cigarette consumption and tobacco dependence did not alter these results substantially.
Conclusions:
Our data, taken together with previous recent studies, provide some support for a weak association between this variant and short-term smoking cessation in treatment-seeking smokers, which does not seem to operate only among those receiving nicotine replacement therapy. Moreover, the rs1051730 variant may not merely operate as a marker for dependence or heaviness of smoking.
doi:10.1093/ntr/ntr106
PMCID: PMC3179672  PMID: 21690317
3.  Association Between Genetic Variants on Chromosome 15q25 Locus and Objective Measures of Tobacco Exposure 
Background
Two single-nucleotide polymorphisms, rs1051730 and rs16969968, located within the nicotinic acetylcholine receptor gene cluster on chromosome 15q25 locus, are associated with heaviness of smoking, risk for lung cancer, and other smoking-related health outcomes. Previous studies have typically relied on self-reported smoking behavior, which may not fully capture interindividual variation in tobacco exposure.
Methods
We investigated the association of rs1051730 and rs16969968 genotype (referred to as rs1051730–rs16969968, because these are in perfect linkage disequilibrium and interchangeable) with both self-reported daily cigarette consumption and biochemically measured plasma or serum cotinine levels among cigarette smokers. Summary estimates and descriptive statistical data for 12 364 subjects were obtained from six independent studies, and 2932 smokers were included in the analyses. Linear regression was used to calculate the per-allele association of rs1051730–rs16969968 genotype with cigarette consumption and cotinine levels in current smokers for each study. Meta-analysis of per-allele associations was conducted using a random effects method. The likely resulting association between genotype and lung cancer risk was assessed using published data on the association between cotinine levels and lung cancer risk. All statistical tests were two-sided.
Results
Pooled per-allele associations showed that current smokers with one or two copies of the rs1051730–rs16969968 risk allele had increased self-reported cigarette consumption (mean increase in unadjusted number of cigarettes per day per allele = 1.0 cigarette, 95% confidence interval [CI] = 0.57 to 1.43 cigarettes, P = 5.22 × 10−6) and cotinine levels (mean increase in unadjusted cotinine levels per allele = 138.72 nmol/L, 95% CI = 97.91 to 179.53 nmol/L, P = 2.71 × 10−11). The increase in cotinine levels indicated an increased risk of lung cancer with each additional copy of the rs1051730–rs16969968 risk allele (per-allele odds ratio = 1.31, 95% CI = 1.21 to 1.42).
Conclusions
Our data show a stronger association of rs1051730–rs16969968 genotype with objective measures of tobacco exposure compared with self-reported cigarette consumption. The association of these variants with lung cancer risk is likely to be mediated largely, if not wholly, via tobacco exposure.
doi:10.1093/jnci/djs191
PMCID: PMC3352832  PMID: 22534784
4.  Effects of 7.5% carbon dioxide (CO2) inhalation and ethnicity on face memory 
Physiology & Behavior  2015;147:97-101.
The ability to accurately verify facial identity has important forensic implications, but this ability is fallible. Research suggests that anxiety at the time of encoding can impair subsequent recall, but no studies have investigated the effects of anxiety at the time of recall in an experimental paradigm. This study addresses this gap using the carbon dioxide (CO2) model of anxiety induction. Thirty participants completed two inhalations: one of 7.5% CO2-enriched air and one of medical air (i.e., placebo). Prior to each inhalation, participants were presented with 16 facial images (50% own-ethnicity, 50% other-ethnicity). During the inhalation they were required to identify which faces had been seen before from a set of 32 images (16 seen-before and 16 novel images). Identification accuracy was lower during CO2 inhalation compared to air (F[1,29] = 5.5, p = .026, ηp2 = .16), and false alarm rate was higher for other-ethnicity faces compared to own-ethnicity faces (F[1,29] = 11.3, p = .002, ηp2 = .28). There was no evidence of gas by ethnicity interactions for accuracy or false alarms (ps > .34). Ratings of decision confidence did not differ by gas condition, suggesting that participants were unaware of differences in performance. These findings suggest that anxiety, at the point of recognition, impairs facial identification accuracy. This has substantial implications for eyewitness memory situations, and suggests that efforts should be made to attenuate the anxiety in these situations in order to improve the validity of identification.
Highlights
•Use of carbon dioxide challenge to investigate acute anxiety effects on face memory•Investigation of the “own-ethnicity” effect and its interaction with acute anxiety•Results show decreased accuracy for face memory during acutely anxious states.•Results show increased false identifications when viewing other ethnicity faces.•Efforts should be made to attenuate anxiety in eye witness situations.
doi:10.1016/j.physbeh.2015.04.027
PMCID: PMC4465959  PMID: 25890273
Anxiety; 7.5% CO2; Eyewitness memory; Face recognition; Other-ethnicity effect
5.  Interventions for smoking cessation in hospitalised patients 
Background
Smoking contributes to reasons for hospitalisation, and the period of hospitalisation may be a good time to provide help with quitting.
Objectives
To determine the effectiveness of interventions for smoking cessation that are initiated for hospitalised patients.
Search methods
We searched the Cochrane Tobacco Addiction Group register which includes papers identified from CENTRAL, MEDLINE, EMBASE and PsycINFO in December 2011 for studies of interventions for smoking cessation in hospitalised patients, using terms including (hospital and patient*) or hospitali* or inpatient* or admission* or admitted.
Selection criteria
Randomized and quasi-randomized trials of behavioural, pharmacological or multicomponent interventions to help patients stop smoking, conducted with hospitalised patients who were current smokers or recent quitters (defined as having quit more than one month before hospital admission). The intervention had to start in the hospital but could continue after hospital discharge. We excluded studies of patients admitted to facilities that primarily treat psychiatric disorders or substance abuse, studies that did not report abstinence rates and studies with follow-up of less than six months. Both acute care hospitals and rehabilitation hospitals were included in this update, with separate analyses done for each type of hospital.
Data collection and analysis
Two authors extracted data independently for each paper, with disagreements resolved by consensus.
Main results
Fifty trials met the inclusion criteria. Intensive counselling interventions that began during the hospital stay and continued with supportive contacts for at least one month after discharge increased smoking cessation rates after discharge (risk ratio (RR) 1.37, 95% confidence interval (CI) 1.27 to 1.48; 25 trials). A specific benefit for post-discharge contact compared with usual care was found in a subset of trials in which all participants received a counselling intervention in the hospital and were randomly assigned to post-discharge contact or usual care. No statistically significant benefit was found for less intensive counselling interventions. Adding nicotine replacement therapy (NRT) to an intensive counselling intervention increased smoking cessation rates compared with intensive counselling alone (RR 1.54, 95% CI 1.34 to 1.79, six trials). Adding varenicline to intensive counselling had a non-significant effect in two trials (RR 1.28, 95% CI 0.95 to 1.74). Adding bupropion did not produce a statistically significant increase in cessation over intensive counselling alone (RR 1.04, 95% CI 0.75 to 1.45, three trials). A similar pattern of results was observed in a subgroup of smokers admitted to hospital because of cardiovascular disease (CVD). In this subgroup, intensive intervention with follow-up support increased the rate of smoking cessation (RR 1.42, 95% CI 1.29 to 1.56), but less intensive interventions did not. One trial of intensive intervention including counselling and pharmacotherapy for smokers admitted with CVD assessed clinical and health care utilization endpoints, and found significant reductions in all-cause mortality and hospital readmission rates over a two-year follow-up period. These trials were all conducted in acute care hospitals. A comparable increase in smoking cessation rates was observed in a separate pooled analysis of intensive counselling interventions in rehabilitation hospitals (RR 1.71, 95% CI 1.37 to 2.14, three trials).
Authors' conclusions
High intensity behavioural interventions that begin during a hospital stay and include at least one month of supportive contact after discharge promote smoking cessation among hospitalised patients. These interventions are effective regardless of the patient's admitting diagnosis and are effective in rehabilitation settings as well as acute care hospitals. lnterventions of lower intensity or shorter duration have not been shown to be effective in this setting. This update found that adding NRT to intensive counselling significantly increases cessation rates over counselling alone. There is insufficient direct evidence to conclude that adding bupropion or varenicline to intensive counselling increases cessation rates over what is achieved by counselling alone.
doi:10.1002/14651858.CD001837.pub3
PMCID: PMC4498489  PMID: 22592676
6.  Association of COMT Val108/158Met Genotype and Cigarette Smoking in Pregnant Women 
Nicotine & Tobacco Research  2010;13(2):55-63.
Introduction:
Smoking behaviors, including heaviness of smoking and smoking cessation, are known to be under a degree of genetic influence. The enzyme catechol O-methyltransferase (COMT) is of relevance in studies of smoking behavior and smoking cessation due to its presence in dopaminergic brain regions. While the COMT gene is therefore one of the more promising candidate genes for smoking behavior, some inconsistencies have begun to emerge.
Methods:
We explored whether the rs4680 A (Met) allele of the COMT gene predicts increased heaviness of smoking and reduced likelihood of smoking cessation in a large population-based cohort of pregnant women. We further conducted a meta-analysis of published data from community samples investigating the association of this polymorphism with heaviness of smoking and smoking status.
Results:
In our primary sample, the A (Met) allele was associated with increased heaviness of smoking before pregnancy but not with the odds of continuing to smoke in pregnancy either in the first trimester or in the third trimester. Meta-analysis also indicated modest evidence of association of the A (Met) allele with increased heaviness of smoking but not with persistent smoking.
Conclusions:
Our data suggest a weak association between COMT genotype and heaviness of smoking, which is supported by our meta-analysis. However, it should be noted that the strength of evidence for this association was modest. Neither our primary data nor our meta-analysis support an association between COMT genotype and smoking cessation. Therefore, COMT remains a plausible candidate gene for smoking behavior phenotypes, in particular, heaviness of smoking.
doi:10.1093/ntr/ntq209
PMCID: PMC3028189  PMID: 21106664
8.  Weekly versus basic smoking cessation support in primary care: a randomised controlled trial 
Thorax  2007;62(10):898-903.
Background
There is insufficient and conflicting evidence about whether more intensive behavioural support is more effective than basic behavioural support for smoking cessation and whether primary care nurses can deliver effective behavioural support.
Methods
A randomised controlled trial was performed in 26 UK general practices. 925 smokers of ⩾10 cigarettes per day were randomly allocated to basic or weekly support. All participants were seen before quitting, telephoned around quit day, and seen 1 and 4 weeks after the initial appointment (basic support). Participants receiving weekly support had an additional telephone call at 10 days and 3 weeks after the initial appointment and an additional visit at 2 weeks to motivate adherence to nicotine replacement and renew quit attempts. 15 mg/16 h nicotine patches were given to all participants. The outcome was assessed by intention to treat analyses of the percentage confirmed sustained abstinence at 4, 12, 26 and 52 weeks after quit day.
Results
Of the 469 and 456 participants in the basic and weekly arms, the numbers (%) who quit and the percentage difference were 105 (22.4%) vs 102 (22.4%), 0.1% (95% CI −5.3% to 5.5%) at 4 weeks, 66 (14.1%) vs 52 (11.4%), −2.6% (95% CI −6.9% to 1.7%) at 12 weeks, 50 (10.7%) vs 40 (8.8%), −1.9% (95% CI −5.7% to 2.0%) at 26 weeks and 36 (7.7%) vs 30 (6.6%), −1.1% (95% CI −4.4% to 2.3%) at 52 weeks.
Conclusions
The absolute quit rates achieved are those expected from nicotine replacement alone, implying that neither basic nor weekly support were effective. Primary care smoking cessation treatment should provide pharmacotherapy with sufficient support only to ensure it is used appropriately, and those in need of support should be referred to specialists.
doi:10.1136/thx.2006.071837
PMCID: PMC2094265  PMID: 17483139
9.  The association of rs1051730 genotype on adherence to and consumption of prescribed nicotine replacement therapy dose during a smoking cessation attempt 
Drug and Alcohol Dependence  2015;151:236-240.
Highlights
•We explore the impact of rs1051730 on nicotine replacement therapy (NRT) use in a smoking cessation trial.•Outcomes were NRT prescription adherence rate (%) and daily consumption (mg).•rs1051730 was associated with both outcomes at 7 days post quit attempt.•Each copy of the minor allele corresponded to a 1 mg decrease in daily NRT consumption.•No evidence of effect of genotype on either outcome observed at 28 days.
Introduction
While nicotine replacement therapy (NRT) is an effective pharmacological smoking cessation treatment, its efficacy is influenced by adherence to and consumption of the prescribed dose. The genetic variant rs1051730 in the nicotinic receptor gene cluster CHRNA5-A3-B4 influences smoking quantity. The aim of this study was to explore the impact of rs1051730 genotype on adherence to and consumption of NRT prescription following a smoking cessation attempt.
Methods
Secondary analysis of data from a pharmacogenetic smoking cessation trial. Participants (n = 448) were prescribed a daily dose of NRT for four weeks post quit attempt, and monitored during weekly clinic visits. Outcome measures were NRT prescription adherence rate (%) and average daily NRT consumption (mg) at 7- and 28-days after the quit attempt.
Results
An association between rs1051730 genotype and both outcome measures was observed at 7-days after the quit date. Each copy of the minor allele corresponded to a 2.9% decrease in adherence to prescribed NRT dose (P = 0.044), and a 1.0 mg decrease in daily NRT consumption (P = 0.026). Adjusting for number of cigarettes smoked during this period only slightly attenuated these associations. There was no clear statistical evidence of an association between genotype and adherence or consumption at 28-days.
Conclusions
This is the first study to evaluate the impact of rs1051730 genotype on consumption of and adherence to NRT prescription during a smoking cessation attempt. We observed an association between this variant and both outcome measures at 7-days; however, this was only moderate. These findings require replication in an independent sample.
doi:10.1016/j.drugalcdep.2015.03.035
PMCID: PMC4462564  PMID: 25891233
Smoking; Nicotine replacement therapy; Cessation; Genetics
10.  5-HTTLPR Genotype and Anxiety-Related Personality Traits: A meta-analysis and new data 
We investigated the strength of evidence for association of the 5-HTTLPR polymorphism and the personality trait of Harm Avoidance. We used new primary data from a large sample of adults drawn from the Finnish population. We also applied meta-analytic techniques to synthesize existing published data. The large number studies of the 5-HTTLPR polymorphism allowed us to apply a formal test of publication bias, as well as formally investigate the impact of potential moderating factors such as measurement instrument.
Univariate ANOVA of primary data (n = 3,872), with 5-HTTLPR genotype as a between-groups factor, indicated no evidence of association with Harm Avoidance (p = 0.99). Meta-analysis indicated no evidence of significant association of 5-HTTLPR with Harm Avoidance (d = 0.02, p = 0.37), or EPQ Neuroticism (d = 0.01, p = 0.71), although there was evidence of association with NEO Neuroticism (d = 0.18, p < 0.001).
Our analyses indicate that the 5-HTTLPR variant is not associated with Harm Avoidance. Together with our previous analyses of a large sample of participants with extreme Neuroticism scores (defined by the EPQ), we have data that excludes a meaningful genetic effect of the 5-HTTLPR on two measures of anxiety-related personality traits. There remains the possibility that the variant influences the NEO personality questionnaire measure of Neuroticism. However, a large, well-powered primary study is required to test this hypothesis directly and adequately.
doi:10.1002/ajmg.b.30808
PMCID: PMC2819421  PMID: 18546120
5-HTTLPR; Genotype; Meta-Analysis; Neuroticism; Harm Avoidance
11.  The endophenotype concept in psychiatric genetics 
Psychological Medicine  2006;37(2):163-180.
The idea that some phenotypes bear a closer relationship to the biological processes that give rise to psychiatric illness than diagnostic categories has attracted considerable interest. Much effort has been devoted to finding such endophenotypes, partly because it is believed that the genetic basis of endophenotypes will be easier to analyse than that of psychiatric disease. This belief depends in part on the assumption that the effect sizes of genetic loci contributing to endophenotypes are larger than those contributing to disease susceptibility, hence increasing the chance that genetic linkage and association tests will detect them. We examine this assumption by applying meta-analytical techniques to genetic association studies of endophenotypes. We find that the genetic effect sizes of the loci examined to date are no larger than those reported for other phenotypes. A review of the genetic architecture of traits in model organisms also provides no support for the view that the effect sizes of loci contributing to phenotypes closer to the biological basis of disease is any larger than those contributing to disease itself. While endophenotype measures may afford greater reliability, it should not be assumed that they will also demonstrate simpler genetic architecture.
doi:10.1017/S0033291706008750
PMCID: PMC2829981  PMID: 16978446
12.  Ventral Striatum/Nucleus Accumbens Activation to Smoking-Related Pictorial Cues in Smokers and Nonsmokers: A Functional Magnetic Resonance Imaging Study 
Biological psychiatry  2005;58(6):488-494.
Background
Converging evidence from several theories of the development of incentive-sensitization to smoking-related environmental stimuli suggests that the ventral striatum plays an important role in the processing of smoking-related cue reactivity.
Methods
Twenty-six healthy right-handed volunteers (14 smokers and 12 nonsmoking controls) underwent functional magnetic resonance imaging (fMRI) during which neutral and smoking-related images were presented. Region of interest analyses were performed within the ventral striatum/nucleus accumbens (VS/NAc) for the contrast between smoking-related (SR) and nonsmoking related neutral (N) cues.
Results
Group activation for SR versus N cues was observed in smokers but not in nonsmokers in medial orbitofrontal cortex, superior frontal gyrus, anterior cingulate cortex, and posterior fusiform gyrus using whole-brain corrected Z thresholds and in the ventral VS/NAc using uncorrected Z-statistics (smokers Z = 3.2). Region of interest analysis of signal change within ventral VS/NAc demonstrated significantly greater activation to SR versus N cues in smokers than controls.
Conclusions
This is the first demonstration of greater VS/NAc activation in addicted smokers than nonsmokers presented with smoking-related cues using fMRI. Smokers, but not controls, demonstrated activation to SR versus N cues in a distributed reward signaling network consistent with cue reactivity studies of other drugs of abuse.
doi:10.1016/j.biopsych.2005.04.028
PMCID: PMC4439461  PMID: 16023086
Nucleus accumbens; smoking; nicotine; tobacco; cue reactivity; fMRI
13.  Genetic variation in the serotonin pathway and smoking cessation with nicotine replacement therapy: New data from the Patch in Practice trial and pooled analyses 
Drug and alcohol dependence  2008;98(0):77-85.
The serotonin pathway has been implicated in nicotine dependence and may influence smoking cessation. Therefore, 792 cigarette smokers from the Patch in Practice trial were genotyped for the tryptophan hydroxylase (TPH1 A779C), serotonin transporter (SLC6A4 5-HTTLPR), and 5-HT1A (HTR1A C-1019G) polymorphisms. Cox regression analysis did not demonstrate significant effects of any of the three genotypes on relapse to smoking: TPH1 (Reference AA; AC: hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.78, 1.24, p = 0.90; CC: HR 0.93, 95% CI 0.73, 1.18, p = 0.55); 5-HTTLPR (Reference LL; SL: HR 1.01, 95% CI 0.85, 1.20, p = 0.90; SS: HR 1.13, 95% CI 0.91, 1.39, p = 0.27); HTR1A (Reference CC; CG: HR 1.04, 95% CI 0.86, 1.25, p = 0.70; GG: HR 1.01, 95% CI 0.82, 1.24, p = 0.93). Moreover, pooled analyses of data from all three extant pharmacogenetic NRT trials (N= 1398) found no significant effect of 5-HTTLPR genotype on continuous abstinence at 12-week (Reference LL; SL: odds ratio (OR) = 1.25, 95% CI 0.89, 1.74, p = 0.19; SS: OR= 1.31, 95% CI 0.86, 1.98, p = 0.21) or 26-week follow-up (Reference LL; SL: OR= 0.93, 95% CI 0.64, 1.33, p = 0.68; SS: OR= 1.00, 95% CI 0.63, 1.58, p = 1.00). These data do not support a statistically or clinically significant moderating effect of these specific 5-HT pathway genetic variants on smoking cessation. However, the possibility remains that other variants in these or other 5-HT genes may influence NRT efficacy for smoking cessation in treatment seeking smokers.
doi:10.1016/j.drugalcdep.2008.04.013
PMCID: PMC4439462  PMID: 18562131
Smoking cessation; Tryptophan hydroxylase; Serotonin transporter; 5-HT1A receptor; Nicotine replacement therapy; Pharmacogenetics
14.  Credible genetic associations? 
The proliferation in genetic association studies, and the recurring failure of initially promising findings to robustly replicate, demonstrates the need for stringent standards to ensure the identification of credible associations. The Human Genome Epidemiology Network has recently published intermin guideliness on evidential criteria for genetic association studies. These are reviewed, and their value and importance discussed, as well as the impact these guidelines will have on the conduct of genetic association studies.
PMCID: PMC3076746  PMID: 21537450
Genetic association; replication; HuGENet; Meta-Analysis
15.  Serotonin Transporter (5-HTTLPR) Genotype and Amygdala Activation: A Meta-Analysis 
Biological psychiatry  2007;63(9):852-857.
Background:
We evaluated the magnitude of the reported associations between amygdala activation and the serotonin transporter gene linked polymorphic region (5-HTTLPR) and the likely effect size of this relationship.
Methods:
We used meta-analytic techniques to combine data from existing published and unpublished studies. We also tested for possible publication bias and explored possible moderating influences on any association, such as sample ancestry.
Results:
Our results provide support for the association of the 5-HTTLPR polymorphism and amygdala activation and suggest that this locus may account for up to 10% of phenotypic variance. Although we did not observe evidence for potential publication bias in our main analysis, this was due in part to efforts to obtain unpublished data pertinent to this meta-analysis, and when three unpublished data sets were excluded we did observe evidence of such bias. We also observed evidence that the first published study may provide an overestimate of the true effect size, which is consistent with findings from genetic association studies of other phenotypes.
Conclusions:
Although our analysis provides support for the association of the 5-HTTLPR polymorphism and amygdala activation, it also suggests that most studies to date are nevertheless lacking in statistical power. Increasing the sample sizes of future imaging genetics studies will allow a more accurate characterization of any true effect size and afford adequate power to examine the impact of multiple polymorphisms that likely work in concert to affect gene function and, in turn, bias neural processes mediating dispositional traits such as temperament and personality.
doi:10.1016/j.biopsych.2007.08.016
PMCID: PMC2755289  PMID: 17949693
5-HTTLPR; amygdala; fMRI; meta-analysis; serotonin transporter gene
16.  No Own-Age Advantage in Children’s Recognition of Emotion on Prototypical Faces of Different Ages 
PLoS ONE  2015;10(5):e0125256.
We test whether there is an own-age advantage in emotion recognition using prototypical younger child, older child and adult faces displaying emotional expressions. Prototypes were created by averaging photographs of individuals from 6 different age and sex categories (male 5–8 years, male 9–12 years, female 5–8 years, female 9–12 years, adult male and adult female), each posing 6 basic emotional expressions. In the study 5–8 year old children (n = 33), 9–13 year old children (n = 70) and adults (n = 92) labelled these expression prototypes in a 6-alternative forced-choice task. There was no evidence that children or adults recognised expressions better on faces from their own age group. Instead, child facial expression prototypes were recognised as accurately as adult expression prototypes by all age groups. This suggests there is no substantial own-age advantage in children’s emotion recognition.
doi:10.1371/journal.pone.0125256
PMCID: PMC4433217  PMID: 25978656
17.  Does smoking reduction worsen mental health? A comparison of two observational approaches 
BMJ Open  2015;5(5):e007812.
Objectives
The association between smoking reduction and mental health is of particular interest given that many smokers report that smoking offers mental health benefits. We aimed to assess the association between smoking reduction and change in mental health using two different analytical approaches to determine if there was any evidence of an association. There were no prior hypotheses.
Design
A secondary analysis of prospective individual level patient data from 5 merged placebo-controlled randomised trials of nicotine replacement therapy for smoking reduction.
Participants
All participants were adult smokers, selected because they wanted to reduce but not stop smoking, and had smoked for at least 3 years. Participants were excluded if they were pregnant, breastfeeding, under psychiatric care, deemed to be unfit by a general practitioner, or part of a cessation programme. 2066 participants were enrolled in the trials, 177 participants were biologically validated as prolonged reducers, and 509 as continuing smokers at both 6-week and 18-week follow-ups.
Primary outcome
Change in mental health from baseline to an 18-week follow-up was measured using the emotional well-being subscale on the Short Form Health Survey-36.
Results
After adjustment for confounding variables, the differences for reducers compared with continuing smokers were: regression modelling −0.6 (95% CI −4.4 to 3.2) and propensity score matching 1.1 (95% CI −2.0 to 4.1).
Conclusions
Smoking reduction, sustained for at least 12 weeks, was not associated with change in mental health, suggesting that reducing smoking was no better or worse for mental health than continuing smoking. Clinicians offering smoking reduction as a route to quit can be confident that, on average, smoking reduction is not associated with negative change in mental health.
doi:10.1136/bmjopen-2015-007812
PMCID: PMC4442156  PMID: 25979871
MENTAL HEALTH; Smoking Reduction; Tobacco
18.  Publication and other reporting biases in cognitive sciences: detection, prevalence and prevention 
Trends in cognitive sciences  2014;18(5):235-241.
Recent systematic reviews and empirical evaluations of the cognitive sciences literature suggest that publication and other reporting biases are prevalent across diverse domains of cognitive science. This review summarizes the various forms of publication and reporting biases and other questionable research practices, and overviews the available methods for probing into their existence. We discuss the available empirical evidence for the presence of such biases across the neuroimaging, animal, other pre-clinical, psychological, clinical trials, and genetics literature in the cognitive sciences. We also highlight emerging solutions (from study design to data analyses and reporting) to prevent bias and improve the fidelity in the field of cognitive science research.
doi:10.1016/j.tics.2014.02.010
PMCID: PMC4078993  PMID: 24656991
publication bias; reporting bias; cognitive sciences; neuroscience; bias
19.  Adolescent cannabis and tobacco use and educational outcomes at age 16: birth cohort study 
Addiction (Abingdon, England)  2015;110(4):658-668.
Aims
To investigate the relationship between cannabis and tobacco use by age 15 and subsequent educational outcomes.
Design
Birth cohort study.
Setting
England.
Participants
The sample was drawn from the Avon Longitudinal Study of Parents and Children; a core sample of 1155 individuals had complete information on all the variables.
Measurements
The main exposures were cannabis and tobacco use at age 15 assessed in clinic by computer-assisted questionnaire and serum cotinine. The main outcomes were performance in standardized assessments at 16 [Key Stage 4, General Certificate of Secondary Education (GCSE)] in English and mathematics (mean scores), completion of five or more assessments at grade C level or higher and leaving school having achieved no qualifications. Analyses were sequentially adjusted for multiple covariates using a hierarchical approach. Covariates considered were: maternal substance use (ever tobacco or cannabis use, alcohol use above recommended limits); life course socio-economic position (family occupational class, maternal education, family income); child sex; month and year of birth; child educational attainment prior to age 11 (Key Stage 2); child substance use (tobacco, alcohol and cannabis) prior to age 15 and child conduct disorder.
Findings
In fully adjusted models both cannabis and tobacco use at age 15 were associated with subsequent adverse educational outcomes. In general, the dose–response effect seen was consistent across all educational outcomes assessed. Weekly cannabis use was associated negatively with English GCSE results [grade point difference (GPD), –5.93, 95% confidence interval (CI) = –8.34, –3.53] and with mathematics GCSE results (GPD, –6.91, 95% CI = –9.92, –3.89). Daily tobacco smoking was associated negatively with English GCSE (GPD, –11.90, 95% CI = –13.47, –10.33) and with mathematics GCSE (GPD, –16.72, 95% CI = –18.57, –14.86). The greatest attenuation of these effects was seen on adjustment for other substance use and conduct disorder. Following adjustment, tobacco appeared to have a consistently stronger effect than cannabis.
Conclusions
Both cannabis and tobacco use in adolescence are associated strongly with subsequent adverse educational outcomes. Given the non-specific patterns of association seen and the attenuation of estimates on adjustment, it is possible that these effects arise through non-causal mechanisms, although a causal explanation cannot be discounted. © 2015 Society for the Study of Addiction
doi:10.1111/add.12827
PMCID: PMC4405050  PMID: 25488831
ALSPAC; cannabis use; cotinine; education; English; GCSE; mathematics; school dropout; smoking
20.  Associations of Cannabis and Cigarette Use with Depression and Anxiety at Age 18: Findings from the Avon Longitudinal Study of Parents and Children 
PLoS ONE  2015;10(4):e0122896.
Introduction
Substance use is associated with common mental health disorders, but the causal effect of specific substances is uncertain. We investigate whether adolescent cannabis and cigarette use is associated with incident depression and anxiety, while attempting to account for confounding and reverse causation.
Methods
We used data from ALSPAC, a UK birth cohort study, to investigate associations between cannabis or cigarettes (measured at age 16) and depression or anxiety (measured at age 18), before and after adjustment for pre-birth, childhood and adolescent confounders. Our imputed sample size was 4561 participants.
Results
Both cannabis (unadjusted OR 1.50, 95% CI 1.26, 1.80) and cigarette use (OR 1.37, 95% CI 1.16, 1.61) increased the odds of developing depression. Adjustment for pre-birth and childhood confounders partly attenuated these relationships though strong evidence of association persisted for cannabis use. There was weak evidence of association for cannabis (fully adjusted OR 1.30, 95% CI 0.98, 1.72) and insufficient evidence for association for cigarette use (fully adjusted OR = 0.97, 95% CI 0.75, 1.24) after mutually adjusting for each other, or for alcohol or other substance use. Neither cannabis nor cigarette use were associated with anxiety after adjustment for pre-birth and childhood confounders.
Conclusions
Whilst evidence of association between cannabis use and depression persisted after adjusting for pre-term and childhood confounders, our results highlight the difficulties in trying to estimate and interpret independent effects of cannabis and tobacco on psychopathology. Complementary methods are required to robustly examine effects of cannabis and tobacco on psychopathology.
doi:10.1371/journal.pone.0122896
PMCID: PMC4395304  PMID: 25875443
21.  Fear of Negative Evaluation Biases Social Evaluation Inference: Evidence from a Probabilistic Learning Task 
PLoS ONE  2015;10(4):e0119456.
Background
Fear of negative evaluation (FNE) defines social anxiety yet the process of inferring social evaluation, and its potential role in maintaining social anxiety, is poorly understood. We developed an instrumental learning task to model social evaluation learning, predicting that FNE would specifically bias learning about the self but not others.
Methods
During six test blocks (3 self-referential, 3 other-referential), participants (n = 100) met six personas and selected a word from a positive/negative pair to finish their social evaluation sentences “I think [you are / George is]…”. Feedback contingencies corresponded to 3 rules, liked, neutral and disliked, with P[positive word correct] = 0.8, 0.5 and 0.2, respectively.
Results
As FNE increased participants selected fewer positive words (β = −0.4, 95% CI −0.7, −0.2, p = 0.001), which was strongest in the self-referential condition (FNE × condition 0.28, 95% CI 0.01, 0.54, p = 0.04), and the neutral and dislike rules (FNE × condition × rule, p = 0.07). At low FNE the proportion of positive words selected for self-neutral and self-disliked greatly exceeded the feedback contingency, indicating poor learning, which improved as FNE increased.
Conclusions
FNE is associated with differences in processing social-evaluative information specifically about the self. At low FNE this manifests as insensitivity to learning negative self-referential evaluation. High FNE individuals are equally sensitive to learning positive or negative evaluation, which although objectively more accurate, may have detrimental effects on mental health.
doi:10.1371/journal.pone.0119456
PMCID: PMC4390305  PMID: 25853835
22.  A cost-effectiveness analysis of genetic testing of the DRD2 Taq1A polymorphism to aid treatment choice for smoking cessation 
We conducted a cost-effectiveness analysis of genetic testing for smoking cessation, based on data available from the published pharmacogenetic studies of nicotine replacement therapy and bupropion, and a previous cost-effectiveness analysis of smoking cessation treatments. We use multiparameter evidence synthesis methods to combine evidence on cessation by genotype with evidence on cessation irrespective of genotype (which can be written as a function of genotype-specific parameters). Our intention was to explore the most cost-effective approach to prescribing smoking cessation pharmacotherapy, given the hypothetical availability of a test based on a single-gene variant that has been reported to predict treatment response. We considered four types of treatment: nicotine replacement therapy (NRT) pharmacotherapy, bupropion SR pharmacotherapy, combination NRT and bupropion, and standard care as the control. Two scenarios were investigated, one in which the control represented brief advice and the other in which the control represented individual counseling. Strategies that either do not test for dopamine D2 receptor (DRD2) genotype (each individual receives the same treatment), or do test for DRD2 genotype (treatment allocated according to genotype), were evaluated. Our results indicated that the most cost-effective strategy in our hypothetical example of a single-gene test to aid prescription of smoking cessation pharmacotherapy is to prescribe both NRT and bupropion regardless of genotype, as a first-line treatment for smoking cessation. We conclude that it should not be assumed that genetic tailoring will necessarily be more cost-effective than applying the current “one-size-fits-all” model of pharmacotherapy for smoking cessation. In addition, single-gene tests are unlikely to be cost-effective, partly because the predictive value of these tests is likely to be modest.
doi:10.1080/14622200701767761
PMCID: PMC2257987  PMID: 18188764
23.  Evaluating psychological interventions in a novel experimental human model of anxiety 
Inhalation of 7.5% carbon dioxide increases anxiety and autonomic arousal and provides a novel experimental model of anxiety with which to evaluate pharmacological and psychological treatments for anxiety. To date several psychotropic drugs including benzodiazepines, SSRIs and SNRIs have been evaluated using the 7.5% CO2 model; however, it has yet to be used to evaluate psychological interventions. We compared the effects of two core psychological components of mindfulness-meditation (open monitoring and focused attention) against general relaxation, on subjective, autonomic and neuropsychological outcomes in the 7.5% CO2 experimental model.
32 healthy screened adults were randomized to complete 10 min of guided open monitoring, focused attention or relaxation, immediately before inhaling 7.5% CO2 for 20 min. During CO2-challenge participants completed an eye-tracking measure of attention control and selective attention. Measures of subjective anxiety, blood pressure and heart rate were taken at baseline and immediately following intervention and CO2-challenge.
OM and FA practice reduced subjective feelings of anxiety during 20-min inhalation of 7.5% CO2 compared to relaxation control. OM practice produced a strong anxiolytic effect, whereas the effect of FA was more modest. Anxiolytic OM and FA effects occurred in the absence of group differences in autonomic arousal and eye-movement measures of attention.
Our findings are consistent with neuropsychological models of mindfulness-meditation that propose OM and FA activate prefrontal mechanisms that support emotion regulation during periods of anxiety and physiological hyper-arousal. Our findings complement those from pharmacological treatment studies, further supporting the use of CO2 challenge to evaluate future therapeutic interventions for anxiety.
Highlights
•32 adults randomized to mindfulness/relaxation interventions before 7.5% CO2-challenge.•Mindfulness practice reduced subjective anxiety compared to relaxation control.•Open-monitoring achieved the greatest reduction in experimentally induced anxiety.•There were no group differences in autonomic arousal or attention control.
doi:10.1016/j.jpsychires.2015.02.001
PMCID: PMC4406751  PMID: 25765144
Mindfulness; Anxiety; Experimental medicine; Attention
24.  Bupropion efficacy for smoking cessation is influenced by the DRD2 Taq1A polymorphism: Analysis of pooled data from two clinical trials 
We analyzed pooled data from two comparable randomized placebo-controlled clinical trials of bupropion pharmacotherapy for smoking cessation for which data on DRD2 Taq1A genotype were available. A total of 722 smokers across the two trials were randomized to 10 weeks of sustained-release bupropion hydrochloride or placebo. General estimating equation analysis demonstrated a significant gene × drug interaction (B=0.87, SE=0.34, p=.009). Smokers with the A2/A2 genotype using bupropion were more than three times as likely, relative to placebo, to be abstinent at end of treatment (35.2% vs. 15.1%; OR=3.25, 95% CI 2.00–5.28) and at 6 months of follow-up (26.7% vs. 12.2%; OR=2.81, 95% CI 1.66–4.77), which was attenuated by 12 months (16.3% vs. 10.7%; OR=1.70, 95% CI 0.95–3.05). We found no significant benefit of bupropion relative to placebo on smoking cessation outcomes at any time point in participants with A1/A1 or A1/A2 genotypes. These data suggest that bupropion may be effective for smoking cessation only in a subgroup of smokers with the DRD2 Taq1 A2/A2 genotype.
doi:10.1080/14622200701705027
PMCID: PMC2128730  PMID: 18058343
25.  Pharmacogenetic clinical trial of sustained-release bupropion for smoking cessation 
This randomized, double-blinded, placebo-controlled trial examined genetic influences on treatment response to sustained-release bupropion for smoking cessation. Smokers of European ancestry (N=291), who were randomized to receive bupropion or placebo (12 weeks) plus counseling, were genotyped for the dopamine D2 receptor (DRD2-Taq1A), dopamine transporter (SLC6A3 3′ VNTR), and cytochrome P450 2B6 (CYP2B6 1459 C→T) polymorphisms. Main outcome measures were cotinine-verified point prevalence of abstinence at end of treatment and at 2-, 6-, and 12-month follow-ups post quit date. Using generalized estimating equations, we found that bupropion, compared with placebo, was associated with significantly greater odds of abstinence at all time points (all p values<.01). We found a significant DRD2 × bupropion interaction (B=1.49, SE=0.59, p=.012) and a three-way DRD2 × bupropion × craving interaction on 6-month smoking cessation outcomes (B=−0.45, SE=0.22, p=.038), such that smokers with the A2/A2 genotype demonstrated the greatest craving reduction and the highest abstinence rates with bupropion. Furthermore, there was a significant DRD2 × CYP2B6 interaction (B=1.43, SE=0.56, p=.01), such that individuals with the DRD2-Taq1 A2/A2 genotype demonstrated a higher odds of abstinence only if they possessed the CYP2B6 1459 T/T or C/T genotype. Because the sample size of this study was modest for pharmacogenetic investigations, the results should be interpreted with caution. Although these results require replication, the data suggest preliminarily that the DRD2-Taq1A polymorphism may influence treatment response to bupropion for smoking cessation and, further, that exploration of gene × gene and gene × craving interactions in future, larger studies may provide mechanistic insights into the complex pharmacodynamics of bupropion.
doi:10.1080/14622200701382033
PMCID: PMC2039873  PMID: 17654295

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