Testing the association between tobacco and cannabis use and cognitive functioning: findings from an observational and Mendelian randomization study

Background Although studies have examined the association between tobacco and cannabis use in adolescence with subsequent cognitive functioning, study designs are usually not able to distinguish correlation from causation. Methods Separate patterns of tobacco and cannabis use were derived using longitudinal latent class analysis based on measures assessed on five occasions from age 13–18 in a large UK population cohort (Avon Longitudinal Study of Parents and Children). Cognitive functioning measures comprised of working memory, response inhibition, and emotion recognition assessed at 24 years of age. Mendelian randomization was used to examine the possible causal relationship between smoking initiation, lifetime cannabis use and cognitive functioning. Results We found evidence of a relationship between tobacco and cannabis use and diminished cognitive functioning for each of the outcomes in the observational analyses. There was evidence to suggest that late-onset regular tobacco smokers (b=-0.29, 95 %CI=-0.45 to -0.13), early-onset regular tobacco smokers (b=-0.45, 95 %CI=-0.84 to -0.05), and early-onset regular cannabis users (b=-0.62, 95 %CI=-0.93 to -0.31) showed poorer working memory. Early-onset regular tobacco smokers (b = 0.18, 95 %CI = 0.07 to 0.28), and early-onset regular cannabis users (b = 0.30, 95 %CI = 0.08 to 0.52) displayed poorer ability to inhibit responses. Late-onset regular (b=-0.02, 95 %CI=-0.03 to - 0.00), and early-onset regular tobacco smokers (b=-0.04, 95 %CI=-0.08 to -0.01) showed poorer ability to recognise emotions. Mendelian randomization analyses were imprecise and did not provide additional support for the observational results. Conclusion There was some evidence to suggest that adolescent tobacco and cannabis use were associated with deficits in working memory, response inhibition and emotion recognition. Better powered genetic studies are required to determine whether these associations are causal

Alcohol use and cognitive functioning in young adults : improving causal inference

Background and Aims: There have been few longitudinal studies of association between alcohol use and cognitive functioning in young people. We aimed to examine whether alcohol use is a causal risk factor for deficient cognitive functioning in young adults. Design: Linear regression was used to examine the relationship between longitudinal latent class patterns of binge drinking and subsequent cognitive functioning. Two-sample Mendelian randomisation (MR) tested evidence for the causal relationship between alcohol use and cognitive functioning. Setting: South West England. Participants: The observational study included 3,155 adolescents and their parents (fully adjusted models) from the Avon Longitudinal Study of Parents and Children (ALSPAC). Genetic instruments for alcohol use were based on almost 1,000,000 individuals from the GWAS & Sequencing Consortium of Alcohol and Nicotine use (GSCAN). Genome-wide association studies for cognitive outcomes were based on 2,500 individuals from ALSPAC. Measurements: Binge drinking was assessed at approximately 16, 17, 18, 21, and 23 years. Cognitive functioning comprised working memory, response inhibition, and emotion recognition assessed at 24 years of age. Ninety-nine independent genome-wide significant SNPs associated with ‘number of drinks per week’ were used as the genetic instrument for alcohol consumption. Potential confounders were included in the observational analyses. Findings: Four binge drinking classes were identified: ‘low-risk’ (41%), ‘early-onset monthly’ (19%), ‘adult frequent’ (23%), and ‘early-onset frequent’ (17%). The association between early-onset frequent binge drinking and cognitive functioning: working memory (b=0.09, 95%CI=-0.10 to 0.28), response inhibition (b=0.70, 95%CI=-10.55 to 11.95), and emotion recognition (b=0.01, 95%CI=-0.01 to 0.02) in comparison to low-risk drinkers were inconclusive as to whether a difference was present. Two-sample MR analyses similarly provided little evidence that alcohol use is associated with deficits in working memory using the inverse variance weight (b=0.29, 95%CI=-0.42 to 0.99), response inhibition (b=-0.32, 95%CI=-1.04 to 0.39), and emotion recognition (b=0.03, 95%CI=-0.55 to 0.61). Conclusions: Binge drinking in adolescence and early adulthood may not be causally related to deficiencies in working memory, response inhibition, or emotion recognition in youths

Psychological factors and surgical recovery

SIGLEAvailable from British Library Document Supply Centre-DSC:DXN032236 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Evaluating psychological interventions in a novel experimental human model of anxiety

Inhalation of 7.5% carbon dioxide (CO2) 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 have been evaluated using the 7.5% CO2 model, including benzodiazepines, selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenaline reuptake inhibitors (SNRIs); 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, OM and focused attention, FA) 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 minutes of guided open monitoring, focused attention or relaxation, immediately before inhaling 7.5% CO2 for 20 minutes. 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-minute 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

Early effects of duloxetine on emotion recognition in healthy volunteers

The serotonin-noradrenaline reuptake inhibitor (SNRI) duloxetine is an effective treatment for major depression and generalized anxiety disorder. Neuropsychological models of antidepressant drug action suggest therapeutic effects might be mediated by the early correction of maladaptive biases in emotion processing, including the recognition of emotional expressions. Sub-chronic administration of duloxetine (for two weeks) produces adaptive changes in neural circuitry implicated in emotion processing; however, its effects on emotional expression recognition are unknown. Forty healthy participants were randomized to receive either 14 days of duloxetine (60mg/day, titrated from 30mg after 3 days) or matched placebo (with sham titration) in a double-blind, between-groups, repeated-measures design. On day 0 and day 14 participants completed a computerized emotional expression recognition task that measured sensitivity to the six primary emotions. Thirty eight participants (19 per group) completed their course of tablets and were included in the analysis. Results provide evidence that duloxetine, compared to placebo may reduce the accurate recognition of sadness. Drug effects were driven by changes in participants’ ability to correctly detect subtle expressions of sadness, with greater change observed in the placebo relative to duloxetine group. These effects occurred in the absence of changes in mood. Our preliminary findings require replication, but complement recent evidence that sadness recognition is a therapeutic target in major depression, and a mechanism through which SNRIs could resolve negative biases in emotion processing to achieve therapeutic effects

Personality is of central concern to understand health: towards a theoretical model for health psychology

This paper sets out the case that personality traits are central to health psychology. To achieve this, three aims need to be addressed. First, it is necessary to show that personality influences a broad range of health outcomes and mechanisms. Second, the simple descriptive account of Aim 1 is not sufficient, and a theoretical specification needs to be developed to explain the personality-health link and allow for future hypothesis generation. Third, once Aims 1 and 2 are met, it is necessary to demonstrate the clinical utility of personality. In this review I make the case that all three Aims are met. I develop a theoretical framework to understand the links between personality and health drawing on current theorising in the biology, evolution, and neuroscience of personality. I identify traits (i.e., alexithymia, Type D, hypochondriasis, and empathy) that are of particular concern to health psychology and set these within evolutionary cost-benefit analysis. The literature is reviewed within a three-level hierarchical model (individual, group, and organisational) and it is argued that health psychology needs to move from its traditional focus on the individual level to engage group and organisational levels

IntEgrating Smoking Cessation treAtment into usual online psychological care for people with common mEntal illness: protocol for an online randomised feasibility and pilot study (ESCAPE Digital)

Background: in the UK, smoking prevalence in people with depression (34%) and anxiety (29%) is more than double that of the general population (13%). People who stop smoking improve their mental health with comparable effect sizes found for antidepressants. In England, online psychological therapy is a standard treatment for depression and anxiety. Online therapy is an acceptable setting for smoking cessation support; however, integrated smoking and mental health support is not available. This novel study aims to assess the acceptability and feasibility of an online smoking cessation intervention, and trial procedures, offered alongside online mental health treatment as it offers increased reach to people with common mental health difficulties who smoke.Methods: a two-armed; Intervention (Integrated SilverCloud smoking cessation support) and control group (SilverCloud usual care), pragmatic, randomised controlled feasibility trial. We aim to recruit 500 adult smokers eligible for online mental health treatment. Follow-up will be conducted at 3-months and 6-months. We will assess the acceptability and feasibility of the trial procedures (i.e., recruitment, data completeness, self-reported acceptability and satisfaction) and the intervention (i.e., self-reported quit attempt, engagement with the smoking cessation and mental health programs, smoking cessation medicine and e-cigarette use, self-reported acceptability and satisfaction) and pilot clinical outcomes (i.e., biologically validated smoking abstinence, anxiety, depression, quality of health). Conclusion: if the Trial is successful, a randomised controlled effectiveness trial will follow to examine whether integrated smoking cessation and mental health treatment increases smoking abstinence and improves depression and anxiety compared to usual care.<br/

Investigating the effect of sexual behaviour on oropharyngeal cancer risk: a methodological assessment of Mendelian randomization

Background Human papilloma virus infection is known to influence oropharyngeal cancer (OPC) risk, likely via sexual transmission. However, sexual behaviour has been correlated with other risk factors including smoking and alcohol, meaning independent effects are difficult to establish. We aimed to evaluate the causal effect of sexual behaviour on the risk of OPC using Mendelian randomization (MR). Methods Genetic variants robustly associated with age at first sex (AFS) and the number of sexual partners (NSP) were used to perform both univariable and multivariable MR analyses with summary data on 2641 OPC cases and 6585 controls, obtained from the largest available genome-wide association studies (GWAS). Given the potential for genetic pleiotropy, we performed a number of sensitivity analyses: (i) MR methods to account for horizontal pleiotropy, (ii) MR of sexual behaviours on positive (cervical cancer and seropositivity for Chlamydia trachomatis) and negative control outcomes (lung and oral cancer), (iii) Causal Analysis Using Summary Effect estimates (CAUSE), to account for correlated and uncorrelated horizontal pleiotropic effects, (iv) multivariable MR analysis to account for the effects of smoking, alcohol, risk tolerance and educational attainment. Results In univariable MR, we found evidence supportive of an effect of both later AFS (IVW OR = 0.4, 95%CI (0.3, 0.7), per standard deviation (SD), p = < 0.001) and increasing NSP (IVW OR = 2.2, 95%CI (1.3, 3.8) per SD, p = < 0.001) on OPC risk. These effects were largely robust to sensitivity analyses accounting for horizontal pleiotropy. However, negative control analysis suggested potential violation of the core MR assumptions and subsequent CAUSE analysis implicated pleiotropy of the genetic instruments used to proxy sexual behaviours. Finally, there was some attenuation of the univariable MR results in the multivariable models (AFS IVW OR = 0.7, 95%CI (0.4, 1.2), p = 0.21; NSP IVW OR = 0.9, 95%CI (0.5 1.7), p = 0.76). Conclusions Despite using genetic variants strongly related sexual behaviour traits in large-scale GWAS, we found evidence for correlated pleiotropy. This emphasizes a need for multivariable approaches and the triangulation of evidence when performing MR of complex behavioural traits