Is there a causal relationship between executive function and liability to mental health and substance use? A Mendelian randomisation approach

Background: Executive function consists of several cognitive control processes that are able to regulate lower level processes. Poorer performance in tasks designed to test executive function is associated with a range of psychopathologies such as schizophrenia, major depressive disorder (MDD) and anxiety, as well as with smoking and alcohol consumption. Despite these well-documented associations, whether they reflect causal relationships, and if so in what direction, remains unclear. We aimed to establish whether there is a causal relationship between a latent factor for performance on multiple executive function tasks - which we refer to as common executive function (cEF) - and liability to schizophrenia, MDD, anxiety, smoking initiation, alcohol consumption, alcohol dependence and cannabis use disorder (CUD), and the directionality of any relationship observed. Methods: We used a two-sample bidirectional Mendelian randomisation (MR) approach using genome-wide association study (GWAS) summary data from large cohorts (N=17,310 to 848,460) to examine whether causal relationships exist, and if so in which direction. Results: We found evidence of a causal effect of increased cEF on reduced schizophrenia liability (IVW: OR=0.10; 95% CI 0.05 to 0.19; p-value=3.43x10-12), reduced MDD liability (IVW: OR=0.52; 95% CI 0.38 to 0.72; p-value=5.23x10-05), decreased drinks per week (IVW: β=-0.06; 95% CI -0.10 to -0.02; p-value=0.003), and reduced CUD liability (IVW: OR=0.27; 95% CI 0.12 to 0.61; p-value=1.58x10-03). We also found evidence of a causal effect of increased schizophrenia liability on decreased cEF (IVW: β=-0.04; 95% CI -0.04 to -0.03; p-value=3.25x10-27), as well as smoking initiation on decreased cEF (IVW: β=-0.06; 95%CI -0.09 to -0.03; p-value=6.11x10-05). Conclusion: Our results indicate a potential bidirectional causal relationship between a latent factor measure of executive function (cEF) and schizophrenia liability, a possible causal effect of increased cEF on reduced MDD liability, CUD liability, and alcohol consumption, and a possible causal effect of smoking initiation on decreased cEF. These results suggest that executive function should be considered as a potential risk factor for some mental health and substance use outcomes, and may also be impacted by mental health (particularly schizophrenia). Further studies are required to improve our understanding of the underlying mechanisms of these effects, but our results suggest that executive function may be a promising intervention target. These results may therefore inform the prioritisation of experimental medicine studies (e.g., of executive function interventions), for both mental health and substance use outcomes, to improve the likelihood of successful translation.

Metabolic and lifestyle factors in relation to senile cataract: a Mendelian randomization study

We conducted a Mendelian randomization study to determine the associations of body mass index (BMI), type 2 diabetes (T2D), systolic blood pressure (SBP), coffee and alcohol consumption and smoking initiation with senile cataract. Independent single nucleotide polymorphisms associated with the metabolic and lifestyle factors at the p < 5 × 10–8 were selected as instrument variables. Summary-level data for senile cataract were obtained from the FinnGen consortium (20,157 cases and 154,905 non-cases) and UK Biobank study (6332 cases and 354,862 non-cases). Higher genetically predicted BMI and SBP and genetic predisposition to T2D and smoking initiation were associated with an increased risk of senile cataract. The combined odds ratios were 1.19 (95% confidence interval (CI) 1.09–1.29; p < 0.001) per one standard deviation increase in BMI (~ 4.8 kg/m2), 1.13 (95% CI 1.04–1.23; p = 0.004) per 10 mmHg increase in SBP, 1.06 (95% CI 1.03–1.09; p < 0.001) per one unit increase in log-transformed odds ratio of T2D, and 1.19 (95% CI 1.10–1.29; p < 0.001) per one standard deviation increase in prevalence of smoking initiation. Genetically predicted coffee consumption showed a suggestive association with senile cataract (odds ratio per 50% increase, 1.18, 95% CI 1.00–1.40; p = 0.050). This study suggests causal roles of obesity, T2D, SBP and smoking in senile cataract.

Cigarette smoking and misperceived norms among adults in rural Uganda: a population-based study

BackgroundLittle is known about perceived norms about cigarette smoking in Uganda or the extent to which perceptions drive personal cigarette smoking behaviour.MethodsWe conducted a cross-sectional study in 2016–2018 that targeted all adults who resided within eight villages in Rwampara District, southwestern Uganda. Personal cigarette smoking frequency was elicited by self-report. We also asked participants what they believed to be the cigarette smoking frequency of most other adult men and women in their villages (i.e., perceived norms). Frequent cigarette smoking was defined as 4+ times/week. We compared perceived norms to cigarette smoking frequency reports aggregated at the village level. We used multivariable Poisson regression to estimate the association between perceived norms and personal cigarette smoking behaviour.ResultsAmong 1626 participants (91% response rate), 92 of 719 men (13%) and 6 of 907 women (0.7%) reported frequent smoking. However, 1030 (63%) incorrectly believed most men in their villages smoked cigarettes frequently. Additionally, 116 (7%) incorrectly believed that most women in their villages smoked cigarettes frequently. These misperceptions were pervasive across social strata. Men who misperceived frequent cigarette smoking as the norm among other men in their villages were more likely to smoke frequently themselves (adjusted relative risk=1.49; 95% CI, 1.13 to 1.97).ConclusionsMost adults overestimated cigarette smoking frequency among village peers. Men who incorrectly believed that frequent smoking was the norm were more likely to engage in frequent smoking themselves. Applying a ‘social norms approach’ intervention by promoting existing healthy norms may prevent smoking initiation or motivate reductions in smoking among men in rural Uganda.

Factors Associated with the Dual Use of Electronic Cigarettes and Cigarettes among Thai Undergraduate Students Who Smoked Cigarettes

This study proposed to identify factors associated with the dual use of electronic cigarettes (e-cigarettes) and cigarettes among undergraduate students who smoked cigarettes. This cross-sectional study employed a self-administered, anonymous online questionnaires to collect information from undergraduate smokers in northern Thailand. Of the 494 participants, 82.8% were dual users of e-cigarettes and cigarettes. The two main reasons for using e-cigarettes were an absence of cigarette smoke odor (76.8%) and availability of flavors (70.7%). Undergraduate smokers who initiated smoking at ≥18 years old were more likely to be dual users than those who initiated smoking at younger age (adjusted odds ratio [aOR]: 2.79, 95% confidence intervals [CI]: 1.32–5.89, p = 0.007). Undergraduate smokers who smoked ≥11 cigarettes daily were more likely to be dual users than those who smoked less (aOR: 2.64, 95% CI: 1.52–4.61, p = 0.001). Conversely, undergraduate smokers who had attempted to quit during the past year were less likely to be dual users (aOR: 0.26, 95% CI: 0.12–0.56, p = 0.001). In conclusion, dual use of e-cigarettes and cigarettes among undergraduate smokers was associated with older age at cigarette smoking initiation, a higher number of cigarettes smoked daily, and having no past year’s cigarette quit attempts.

“The Menthol One Is More Friendly”: Young Singaporeans’ Perspectives on Flavored Cigarettes

Over half of the cigarettes sold in Singapore contain added flavors such as menthol. We conducted nine focus group discussions (n = 46) with young (age 20-25) current smokers in Singapore to understand the role of flavors in smoking initiation. We found that flavors triggered the curiosity to experiment with tobacco and e-cigarette products and played an important role in the formation of early cigarette preferences. Menthol-flavored cigarettes were the most appealing to participants due to their smoothness and cooling sensation, described as pleasant against Singapore’s hot and humid climate. While some participants believed that flavored and nonflavored cigarettes were equally harmful, others believed that flavored variants had a lower nicotine content and were therefore less harmful, or that the added chemicals in flavored cigarettes could result in higher toxicant exposures. Thus, among young people in Singapore, flavors appear to play an important role in smoking initiation and there appear to be various misperceptions regarding their harmfulness.

Association Between Initiation, Intensity, and Cessation of Smoking and Mortality Risk in Patients With Cardiovascular Disease: A Cohort Study

Objectives: To examine the effect of smoking status, smoking intensity, duration of smoking cessation and age of smoking initiation on the risk of all-cause and cause-specific mortality among cardiovascular disease (CVD) patients.Design: A population-based prospective cohort study.Setting: The National Health Interview Survey (NHIS) in the U.S. that were linked to the National Death Index (NDI).Participants: 66,190 CVD participants ≥ 18 years of age who were interviewed between 1997 and 2013 in the NHIS linked to the NDI through December 31, 2015.Outcome Measures: The primary outcome was all-cause mortality and the secondary outcome was cause-specific mortality including CVD mortality and cancer mortality.Results: During the mean follow-up of 8.1 years, we documented 22,518 deaths (including 6,473 CVD deaths and 4,050 cancer deaths). In the overall CVD population, former and current smokers had higher risk of all-cause (Former smokers: hazard ratios (HRs), 1.26; 95% confidence interval (CI), 1.21–1.31, P &lt; 0.001; Current smokers: HRs, 1.96; 95%CI, 1.86–2.07, P &lt; 0.001), CVD (Former smokers: HRs, 1.12; 95%CI, 1.05–1.21, P = 0.001; Current smokers: HRs, 1.80; 95%CI, 1.64–1.97, P &lt; 0.001) and cancer mortality (Former smokers: HRs, 1.49; 95%CI, 1.35–1.64, P &lt; 0.001; Current smokers: HRs, 2.78; 95%CI, 2.49–3.09, P &lt; 0.001) than never smokers. Furthermore, similar results were observed when the study subjects were stratified according to the type of CVD. Among current smokers, the risk for cancer mortality increased as the daily number of cigarettes increased, regardless of the specific type of CVD. However, the association of the risk for all-cause and CVD mortality with smoking intensity did not present a dose-response relationship. In participants with angina pectoris or stroke, smoking intensity was inversely associated with deaths from CVD. In addition, the risk for all-cause, CVD and cancer mortality declined as years of smoking cessation increased. Finally, the relative risk of all-cause mortality was not significantly different in individuals with a younger age of smoking initiation.Conclusions: CVD patients who are smokers have an increased risk of all-cause, CVD and cancer mortality, and the risk decreases significantly after quitting smoking. These data further provide strong evidence that supports the recommendation to quit smoking for the prevention of premature deaths among individuals with CVD.

Smoking prevention in adolescents: a cross-sectional and qualitative evaluation of a newly implemented prevention program in Switzerland

ObjectivesIn 2014, a hospital-based smoking prevention programme ‘Nichtrauchen ist clever!’ (NIC!) for adolescents aged 12–14 was initiated. The aim of the study was to evaluate participants’ smoking behaviour and to explore the acceptance of the programme, and participants’ awareness on smoking-related diseases and factors that promote smoking initiation.DesignWe performed a cross-sectional survey to evaluate participant’s acceptance of the NIC! program and their smoking habits. A total of 1658 participants completed the survey between January 2016 and December 2019. A qualitative approach, including analysing feedback from students gathered at 77 prevention events between June 2014 and December 2019, was used to assess their view on reasons for smoking initiation and their knowledge about smoking-related diseases.ResultsTwenty-six per cent (429/1658) have already tried tobacco products (so called triers), specifically cigarettes, electronic (e)-cigarettes and shisha. The use of e-cigarettes was most popular among triers 58% (252/429). Eighty-eight per cent of participants (1408/1604) reported they had acquired good or excellent knowledge about smoking, and 89% (1439/1617) of participants stated that they intend not to smoke in the future. Particularly lung cancer and cancer in general, heart—and vascular diseases were frequently mentioned to be smoking related; where, on the other hand, a large number of relevant smoking-associated diseases were mentioned irregularly. Peer pressure, stress and coolness were identified as reasons for smoking initiation, whereas the influence of marketing and multimedia, as well as socioeconomic—and lifestyle-related factors on smoking behaviour was barely noticed.ConclusionNIC! had a high acceptance among the participants and a large number of students reported relevant gain of knowledge. We identified important knowledge-gaps relating to smoking initiation and smoking-related diseases, helping to improve further smoking prevention approaches.

“If Someone Has It, I’m Gonna Hit It”: Lessons Learned From Minnesota Teens About Vaping

Youth e-cigarette use or “vaping” has increased substantially in the past few years, an escalation attributable to flavored “pod mod” e-cigarette devices that deliver higher levels of nicotine compared with free-base nicotine found in other types of e-cigarettes. Use rates, addiction, and harms are alarming as negative effects from nicotine on adolescent brain development are well documented, and e-cigarette use is predictive of cigarette smoking initiation. This qualitative study examined what drives the appeal of these products through 10 focus groups conducted in 2019 with 67 Minnesota high school students. Focus groups aimed to understand students’ personal experiences and contextual factors that may contribute to current vaping trends and explore opportunities for improved prevention messaging. Study results revealed participants’ divergent perceptions of tobacco products (i.e., vaping vs. e-cigarettes vs. cigarettes) and the benefits and harms of each product. Participants provided insights into why youth vape, describing vaping as an easily accessible coping method to help teens manage stress and anxiety. Peer normalization and invincibility beliefs about harms were also present. Participants generated ideas about prevention messaging, describing the ineffectiveness of prevention messages they currently receive, and expressing the need for accurate information about e-cigarette health risks presented in personalized, nonjudgmental contexts by people they know care about them. These results have clear implications for prevention initiatives and can be used to inform effective prevention strategies, messaging, programming, and policies, some of which are specific to e-cigarette prevention and others that align with the theory of positive youth development.