Concurrent and longitudinal associations of developmental language disorder with peer victimization in adolescence: evidence from a co-twin study

BACKGROUND: Children with developmental language disorder (DLD) experience higher levels of peer victimization than their peers. However, it is not known if such associations reflect genetic and environmental confounding. We used a co-twin control design to investigate the association of language difficulties (DLD and separately poor pragmatic language) with peer victimization and compare the developmental trajectories of peer victimization across adolescence for those with and without language difficulties. METHODS: Participants were 3,400 pairs of twins in the Twins Early Development Study (TEDS), a UK-based population birth cohort. Language abilities were assessed via online tests at age 11 and peer victimization was self-reported at ages 11, 14 and 16. Language difficulties were defined as language abilities at least −1.25 SD below the mean of the TEDS sample. We performed linear regressions and latent growth curve modeling at a population level and within monozygotic and same-sex dizygotic twin pairs. RESULTS: At population level, youth with DLD experienced higher levels of peer victimization at ages 11 (β = 0.27, 95% Confidence Interval (CI) 0.20–0.35), 14 (β = 0.15, 95% CI 0.03–0.27) and 16 (β = 0.17, 95% CI 0.03–0.32) and a sharper decline in peer victimization between ages 11 and 16 compared to their peers without DLD. The associations between DLD and peer victimization were reduced in strength and not statistically significant in within-twin models. Moreover, there was no difference in the rate of change in peer victimization between twin pairs discordant for DLD. Results were similar for the association of poor pragmatic language with peer victimization. CONCLUSIONS: Associations between language difficulties (DLD and separately, poor pragmatic language) and peer victimization were confounded by genetic and shared environmental factors. Identifying specific factors underlying these associations is important for guiding future work to reduce peer victimization among adolescents with language difficulties

Protocol Risk factors for disruptive behaviours: protocol for a systematic review and meta-analysis of quasi-experimental evidence

Introduction: Disruptive behaviour disorders, including oppositional defiant disorder and conduct disorder, are a common set of diagnoses in childhood and adolescence, with global estimates of 5.7%, 3.6% and 2.1% for any disruptive disorder, oppositional defiant disorder and conduct disorder, respectively. There are high economic and social costs associated with disruptive behaviours and the prevalence of these disorders has increased in recent years. As such, disruptive behaviours represent an escalating major public health concern and it is important to understand what factors may influence the risk of these behaviours. Such research would inform interventions that aim to prevent the development of disruptive behaviours. The current review will identify the most stringent evidence of putative risk factors for disruptive behaviour from quasi-experimental studies, which enable stronger causal inference. Methods and analysis: The review will be carried out according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. An electronic search of references published between 1 January 1980 and 1 March 2020 will be conducted using Medline, Embase, PsycINFO and Web of Science. Initial abstract and title screening, full-text screening and data extraction will be completed independently by two reviewers using Evidence for Policy and Practice Information (EPPI)-Reviewer 4 software. Quasi-experimental studies in the English language examining the association between any putative risk factor and a clearly defined measure of disruptive behaviour (eg, a validated questionnaire measure) will be included. We will conduct meta-analyses if we can pool a minimum of three similar studies with the same or similar exposures and outcomes. Ethics and dissemination: The proposed review does not require ethical approval. The results will help to identify risk factors for which there is strong evidence of causal effects on disruptive behaviours and also highlight potential risk factors that require further research. The findings will be disseminated via publication in a peer-reviewed scientific journal and through presentations at international meetings and conferences

Could interventions on physical activity mitigate genomic liability for obesity? Applying the health disparity framework in genetically informed studies

Polygenic scores (PGS) are now commonly available in longitudinal cohort studies, leading to their integration into epidemiological research. In this work, our aim is to explore how polygenic scores can be used as exposures in causal inference-based methods, specifically mediation analyses. We propose to estimate the extent to which the association of a polygenic score indexing genetic liability to an outcome could be mitigated by a potential intervention on a mediator. To do this this, we use the interventional disparity measure approach, which allows us to compare the adjusted total effect of an exposure on an outcome, with the association that would remain had we intervened on a potentially modifiable mediator. As an example, we analyse data from two UK cohorts, the Millennium Cohort Study (MCS, N = 2575) and the Avon Longitudinal Study of Parents and Children (ALSPAC, N = 3347). In both, the exposure is genetic liability for obesity (indicated by a PGS for BMI), the outcome is late childhood/early adolescent BMI, and the mediator and potential intervention target is physical activity, measured between exposure and outcome. Our results suggest that a potential intervention on child physical activity can mitigate some of the genetic liability for childhood obesity. We propose that including PGSs in a health disparity measure approach, and causal inference-based methods more broadly, is a valuable addition to the study of gene-environment interplay in complex health outcomes

Adult Attention Deficit Hyperactivity Disorder and Violence in the Population of England: Does Comorbidity Matter?

It is unclear whether the association between Attention Deficit/Hyperactivity Disorder (ADHD) and violence is explained by ADHD symptoms or co-existing psychopathology. We investigated associations of ADHD and its symptom domains of hyperactivity and inattention, among individuals reporting violence in the UK population. Methods We report data from the Adult Psychiatric Morbidity Survey (2007), a representative sample of the household population of England. A randomly selected sample of 7,369 completed the Adult Self-Report Scale for ADHD and the self-reported violence module, including repetition, injury, minor violence, victims and location of incidents. All models were weighted to account for non-response and carefully adjusted for demography and clinical predictors of violence: antisocial personality, substance misuse and anxiety disorders. Results ADHD was moderately associated with violence after adjustments (OR 1.75, p = .01). Hyperactivity, but not inattention was associated with several indicators of violence in the domestic context (OR 1.16, p = .03). Mild and moderate ADHD symptoms were significantly associated with violence repetition, but not severe ADHD where the association was explained by co-existing disorders. Stratified analyses further indicated that most violence reports are associated with co-occurring psychopathology. Conclusions The direct effect of ADHD on violence is only moderate at the population level, driven by hyperactivity, and involving intimate partners and close persons. Because violence associated with severe ADHD is explained by co-existing psychopathology, interventions should primarily target co-existing disorders

Quasi-experimental evidence on short and long-term consequences of bullying victimization: A meta-analysis

Exposure to bullying victimization is associated with a wide-range of short and long-term adverse outcomes. However, the extent to which these associations reflect a causal influence of bullying victimization remains disputed. Here, we aimed to provide the most stringent evidence regarding the consequences of bullying victimization by meta-analysing all relevant Quasi-Experimental (QE) studies. Multilevel random effects models and meta-regression were employed to (i) estimate the pooled QE-adjusted effect size (Cohen d) for bullying victimization on outcomes and to (ii) evaluate potential sources of heterogeneity. A total of 16 studies were included. We derived 101 QE-estimates from three different methods (twin design, fixed effects analysis, and propensity score matching) for three pools of outcomes (internalizing symptoms, externalizing symptoms, academic difficulties). QE-adjusted effects were small for internalizing symptoms (dadjusted=0.27, 95%CI 0.05;0.49), and smaller for externalizing symptoms (dadjusted=0.15, 95%CI 0.10;0.21) and academic difficulties (dadjusted=0.10, 95%CI 0.06; 0.13). Accounting for a shared rater effect between the exposure and the outcome further reduced the effect for internalizing (dnon-shared rater=0.14, 95%CI 0.05;0.23) and externalizing symptoms (dnon-shared rater=0.06, 95%CI 0.01;0.11). Finally, the adverse effects declined in the long-term, most markedly for internalizing symptoms (dlong-term=0.06, 95%CI -0.01;0.13). Based on the most stringent evidence available to date, findings indicate that bullying victimization may causally impact children’s wellbeing in the short-term, especially anxiety and depression levels. The reduction of adverse effects over time highlights the potential for resilience in individuals who have experienced bullying. Secondary preventive interventions in bullied children should therefore focus on resilience and address children's pre-existing vulnerabilities

Quasi-experimental evidence on short and long-term consequences of bullying victimization: A meta-analysis

Exposure to bullying victimization is associated with a wide-range of short and long-term adverse outcomes. However, the extent to which these associations reflect a causal influence of bullying victimization remains disputed. Here, we aimed to provide the most stringent evidence regarding the consequences of bullying victimization by meta-analysing all relevant Quasi-Experimental (QE) studies. Multilevel random effects models and meta-regression were employed to (i) estimate the pooled QE-adjusted effect size (Cohen d) for bullying victimization on outcomes and to (ii) evaluate potential sources of heterogeneity. A total of 16 studies were included. We derived 101 QE-estimates from three different methods (twin design, fixed effects analysis, and propensity score matching) for three pools of outcomes (internalizing symptoms, externalizing symptoms, academic difficulties). QE-adjusted effects were small for internalizing symptoms (dadjusted=0.27, 95%CI 0.05;0.49), and smaller for externalizing symptoms (dadjusted=0.15, 95%CI 0.10;0.21) and academic difficulties (dadjusted=0.10, 95%CI 0.06; 0.13). Accounting for a shared rater effect between the exposure and the outcome further reduced the effect for internalizing (dnon-shared rater=0.14, 95%CI 0.05;0.23) and externalizing symptoms (dnon-shared rater=0.06, 95%CI 0.01;0.11). Finally, the adverse effects declined in the long-term, most markedly for internalizing symptoms (dlong-term=0.06, 95%CI -0.01;0.13). Based on the most stringent evidence available to date, findings indicate that bullying victimization may causally impact children’s wellbeing in the short-term, especially anxiety and depression levels. The reduction of adverse effects over time highlights the potential for resilience in individuals who have experienced bullying. Secondary preventive interventions in bullied children should therefore focus on resilience and address children's pre-existing vulnerabilities

Sex differences in socioemotional functioning, attentional bias, and gray matter volume in maltreated children:A multilevel investigation

While maltreatment is known to impact social and emotional functioning, threat processing, and neural structure, the potentially dimorphic influence of sex on these outcomes remains relatively understudied. We investigated sex differences across these domains in a large community sample of children aged 10 to 14 years (n = 122) comprising 62 children with verified maltreatment experience and 60 well-matched nonmaltreated peers. The maltreated group relative to the nonmaltreated comparison group exhibited poorer social and emotional functioning (more peer problems and heightened emotional reactivity). Cognitively, they displayed a pattern of attentional avoidance of threat in a visual dot-probe task. Similar patterns were observed in males and females in these domains. Reduced gray matter volume was found to characterize the maltreated group in the medial orbitofrontal cortex, bilateral middle temporal lobes, and bilateral supramarginal gyrus; sex differences were observed only in the supramarginal gyrus. In addition, a disordinal interaction between maltreatment exposure and sex was found in the postcentral gyrus. Finally, attentional avoidance to threat mediated the relationship between maltreatment and emotional reactivity, and medial orbitofrontal cortex gray matter volume mediated the relationship between maltreatment and peer functioning. Similar mediation patterns were observed across sexes. This study highlights the utility of combining multiple levels of analysis when studying the latent vulnerability engendered by childhood maltreatment and yields tentative findings regarding a neural basis of sex differences in long-term outcomes for maltreated children.</p

A curated online resource for SOX10 and pigment cell molecular genetic pathways

We describe the creation of a specialized web-accessible database named the Pigment Cell Gene Resource, which contains information on the genetic pathways that regulate pigment cell development and function. This manually curated database is comprised of two sections, an annotated literature section and an interactive transcriptional network diagram. Initially, this database focuses on the transcription factor SOX10, which has essential roles in pigment cell development and function, but the database has been designed with the capacity to expand in the future, allowing inclusion of many more pigmentation genes

Widespread covariation of early environmental exposures and trait-associated polygenic variation

Although gene-environment correlation is recognized and investigated by family studies and recently by SNP-heritability studies, the possibility that genetic effects on traits capture environmental risk factors or protective factors has been neglected by polygenic prediction models. We investigated covariation between trait-associated polygenic variation identified by genome-wide association studies (GWAS) and specific environmental exposures, controlling for overall genetic relatedness using a genomic-relatedness-matrix restricted maximum-likelihood model. In a UK-representative sample (N=6,710), we find widespread covariation between offspring trait-associated polygenic variation and parental behavior and characteristics relevant to children’s developmental outcomes – independently of population stratification. For instance, offspring genetic risk for schizophrenia was associated with paternal age (R2=0.002; P=1e-04), and offspring education-associated variation was associated with variance in breastfeeding (R2=0.021; P=7e-30), maternal smoking during pregnancy (R2=0.008; P=5e-13), parental smacking (R2=0.01; P=4e-15), household income (R2=0.032; P=1e-22), watching television (R2=0.034; P=5e-47), and maternal education (R2=0.065; P=3e-96). Education-associated polygenic variation also captured covariation between environmental exposures and children’s inattention/hyperactivity, conduct problems, and educational achievement. The finding that genetic variation identified by trait GWAS partially captures environmental risk factors or protective factors has direct implications for risk prediction models and the interpretation of GWAS findings.<br/