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There is considerable variability in developmental outcomes of children whose mothers experience depression. Few longitudinal studies have examined contributions of paternal involvement in the association between maternal postnatal depression (PND) and offspring development. We examined pathways from maternal PND at 8 weeks (Edinburgh Postnatal Depression Scale; total score) to offspring emotional and behavioral development at 7 years (Strengths and Difficulties Questionnaire; total score) through behavioral, affective, and cognitive dimensions of paternal involvement in a U.K.-based birth cohort (Avon Longitudinal Study of Parents and Children; n = 3,434). Analyses were adjusted for baseline confounders and paternal PND (Edinburgh Postnatal Depression Scale; total score) as an intermediate confounder. Maternal PND was strongly associated with offspring development, but this association was not mediated by the combination of all indirect pathways through various dimensions of paternal involvement. Only father--child conflict emerged as a risk factor for adverse offspring development and as a mediator in the association between maternal PND and offspring development (albeit the effect size was small). If found causal, interventions that reduce father-child conflict may reduce the risk of adverse development in offspring of mothers with PND.

ObjectiveTo investigate the genetic architecture of internalizing symptoms in childhood and adolescence.MethodIn 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for sample overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument.ResultsThe meta-analysis of overall internalizing symptoms (INToverall) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66%, 95% CI = 0.84-2.48%, neffective = 132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalizing symptoms showing the highest heritability (5.63%, 95% CI = 3.08%-8.18%). The contribution of additive genetic effects on internalizing symptoms appeared to be stable over age, with overlapping estimates of SNP heritability from early childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the well-being spectrum (|rg| > 0.70), as well as with insomnia, loneliness, attention-deficit/hyperactivity disorder, autism, and childhood aggression (range |rg| = 0.42-0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa.ConclusionGenetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.

Background: Various vitamins and minerals have been implicated in the aetiology of depression. Objective: To estimate the effects of micronutrient exposures on major depressive disorder (MDD) and recurrent depression (rMDD) using Mendelian randomisation (MR), a method using genetic data to estimate causal effects given certain assumptions. Methods: We undertook a comprehensive bidirectional MR study of multiple micronutrient exposures on MDD and rMDD. Summary statistics were obtained from the Psychiatric Genomics Consortium (PGC) genome-wide association studies (GWASs) of MDD (cases = 116,209; controls = 314,566) and rMDD (cases = 17,451; controls = 62,482). Results: None of the micronutrients with available genetic instruments were strongly associated with MDD or rMDD using traditional MR methods. However, using methods to increase analytical power by accounting for genetically correlated variants (e.g., cIVW) highlighted five micronutrients with possible causal effects. Point estimates for rMDD were the largest magnitude, with three micronutrients suggestive of a protective effect: serum iron (ORcIVW 0.90 per SD increase; 95% CI 0.85–0.95; p = 0.0003); erythrocyte copper (ORcIVW 0.97; 95% CI 0.95–0.99; p = 0.0004); and 25(OH) vitamin D (ORcIVW 0.81; 0.66–0.99; p = 0.04). Apparent adverse effects of increased selenium on the risk of MDD (ORcIVW 1.03; 95% CI 1.02–1.05; p = 0.0003) and rMDD (ORcIVW 1.08; 95% CI 1.00–1.08; p = 0.06), and serum magnesium on rMDD (ORcIVW 1.21; 1.01–1.44; p = 0.04); were less consistent between methods and may be driven by pleiotropy. Conclusions: Our results suggest weak evidence for a protective effect of iron, copper and 25(OH)D on major depressive outcomes, with mixed evidence for selenium and magnesium. There was no evidence to support a causal effect of any other micronutrients on MDD or rMDD, although genetic instruments were lacking, with insufficient power to detect small but important effects. Future micronutrient supplementation trials should ensure ample statistical power given modest causal effect estimates and consider potential risks of supplementation, as some micronutrient effect estimates suggested potential harm in excess. [ABSTRACT FROM AUTHOR]

Background Smokers report poorer sleep than nonsmokers and sleep quality deteriorates further during cessation, increasing risk of smoking relapse. Better understanding of the relationship between sleep and relapse-related outcomes could inform novel approaches to smoking cessation support. The aim of this study was to investigate same-day associations of self-reported sleep quality and fatigue severity with factors associated with successful cessation and cessation beliefs, among regular smokers. Methods This cross-sectional observational study (n = 412) collected self-reported sleep quality, fatigue severity, and factors associated with successful cessation and cessation beliefs among regular smokers via an online survey (60% male). Results There was evidence of an association between sleep quality (SQ) and reduced 24-hour (β = −0.12, p =.05) and lifetime (β = −0.09, p =.04) abstinence self-efficacy. In addition, poorer SQ and higher fatigue severity (FS) were associated with increased smoking urges (SQ: β = 0.27, p <.001; FS: β = 0.32, p <.001), increased barriers to cessation (SQ: β = 0.19, p <.001; FS: β = 0.32, p <.001), and increased perceived risks to cessation (SQ: β = 0.18, p <.001; FS: β = 0.26, p <.001). Fatigue severity was weakly associated with increased perceived benefits to cessation (β = 0.12, p =.017). Conclusions Self-reported sleep quality and fatigue severity were associated with multiple factors associated with successful cessation and cessation beliefs. Further research is needed to extend these findings by using different methods to identify the temporal direction of associations and causality. Implications This study is the first to examine associations between sleep quality, fatigue severity, and factors associated with successful cessation and cessation beliefs. Findings show that both sleep quality and fatigue severity are associated with multiple factors associated with successful cessation and could be modifiable targets for future smoking cessation interventions. Furthermore, our data suggest that fatigue severity has an independent effect on multiple factors associated with successful cessation when accounting for sleep quality. This indicates that fatigue, independent of sleep quality, could be an important factor in a quit attempt. [ABSTRACT FROM AUTHOR]

Introduction Although observational data suggest a relationship between headache and smoking, there remain questions about causality. Smoking may increase headache risk, individuals may smoke to alleviate headaches, or smoking and headache may share common risk factors. Mendelian randomization (MR) is a method that uses genetic variants as instruments for making causal inferences about an exposure and an outcome. Aims and Methods First, we conducted logistic regression of observational data in UK Biobank assessing the association between smoking behaviors (smoking status, cigarettes per day amongst daily smokers, and lifetime smoking score) on the risk of self-reported headache (in the last month and for more than 3 months). Second, we used genetic instruments for smoking behaviors and headache (identified in independent genome-wide association studies [GWAS]) to perform bidirectional MR analysis. Results Observationally, there is a weak association between smoking behavior and experiencing headache, with increased cigarettes per day associated with increased headache risk. In the MR analysis, genetic liability to smoking initiation and lifetime smoking increased odds of headache in the last month but not odds of headaches lasting more than 3 months. In the opposite direction, there was weak evidence for higher genetic liability to headaches decreasing the chance of quitting. Conclusions There was weak evidence for a partially bidirectional causal relationship between smoking behaviors and headache in the last month. Given this relationship is distinct from smoking heaviness, it suggests headache and smoking may share common risk factors such as personality traits. Implications Using MR, this study addresses the uncertainty regarding the observed relationship between headache and smoking. There was evidence for weak causal effects of smoking initiation and lifetime smoking (but not smoking heaviness) on likelihood of experiencing headache in the last month, but not over a prolonged period of more than 3 months. Those with higher genetic liability to headaches were also less likely to successfully stop smoking. This partially bidirectional causal relationship distinct from smoking heaviness suggests that observed associations are unlikely due to biological effects of tobacco smoke exposure and may be explained by shared personality traits. [ABSTRACT FROM AUTHOR]

Background Mendelian randomization (MR) is a form of instrumental variable analysis used to investigate causality using observational data. Another important, although less frequently applied, use of this technique is to investigate confounding due to reverse causality. Methods We used a form of reverse MR and data from UK Biobank in a proof-of-principle study to investigate confounding due to reverse causation. Here we focus on the association between alcohol consumption (exposure) and outcomes including educational attainment, and physical and mental health. First, we examined the observational relationship between alcohol consumption and these outcomes. Allele scores were then derived for educational attainment, and physical and mental health, and the association with alcohol consumption (as the outcome) was explored. Sample sizes ranged from 114 941–336 473 in observational analyses and 142 093–336 818 in genetic analyses. Results Conventional observational analyses indicated associations between alcohol consumption and a number of outcomes (e.g. neuroticism, body mass index, educational attainment). Analyses using allele scores suggested evidence of reverse causation for several of these relationships (in particular physical health and educational attainment). Conclusion Allele scores allow us to investigate reverse causation in observational studies. Our findings suggest that observed associations implying beneficial effects of alcohol consumption may be due to confounding by reverse causation in many cases. [ABSTRACT FROM AUTHOR]