Family dysfunction, stressful life events, and mental health problems across development in the offspring of parents with an affective disorder.

BACKGROUND: Offspring of parents with affective disorders (OAD) are at risk of developing a wide range of mental disorders. Deficits in the rearing environment and high levels of stress are well-known risk factors for negative outcomes in OAD. Building on prior research, we aim to examine the longitudinal relationships between family dysfunction, stressful life events, and mental health in OAD and control offspring of parents with no affective disorder. In the present study, we hypothesized that high levels of family dysfunction would be associated with more internalizing and externalizing problems across time in OAD than in controls, and that family dysfunction would mediate the relationship between stressful life events in adolescence and poor mental health in adulthood, particularly in OAD. METHODS: As part of the TRacking Adolescents' Lives Survey (TRAILS), 2230 participants (51% female, Mage = 11.1 years, SD = 0.6, at baseline) and their parents completed measures across six time points, spanning 15 years. Mental health, family dysfunction, and stressful life events were assessed with the Youth and Adult Self-Report, Family Assessment Device, and an in-house measure, respectively. RESULTS: Multi-group structured equation modeling revealed that family dysfunction was linked to internalizing and externalizing problems in OAD, but not controls, across time. Risk status did not moderate family dysfunction's mediation of the relationship between stressful life events and negative outcomes in adulthood. CONCLUSIONS: OAD show high sensitivity to dysfunction in the rearing environment across childhood and adolescence, which supports the use of family based interventions to prevent the development of mental disorders in high-risk youth.

Using parent-offspring pairs and trios to estimate indirect genetic effects in education.

We investigated indirect genetic effects (IGEs), also known as genetic nurture, in education with a novel approach that uses phased data to include parent-offspring pairs in the transmitted/nontransmitted study design. This method increases the power to detect IGEs, enhances the generalizability of the findings, and allows for the study of effects by parent-of-origin. We validated and applied this method in a family-based subsample of adolescents and adults from the Lifelines Cohort Study in the Netherlands (N = 6147), using the latest genome-wide association study data on educational attainment to construct polygenic scores (PGS). Our results indicated that IGEs play a role in education outcomes in the Netherlands: we found significant associations of the nontransmitted PGS with secondary school level in youth between 13 and 24 years old as well as with education attainment and years of education in adults over 25 years old (ß = 0.14, 0.17 and 0.26, respectively), with tentative evidence for larger maternal IGEs. In conclusion, we replicated previous findings and showed that including parent-offspring pairs in addition to trios in the transmitted/nontransmitted design can benefit future studies of parental IGEs in a wide range of outcomes.

Genomics Research of Lifetime Depression in the Netherlands: The BIObanks Netherlands Internet Collaboration (BIONIC) Project.

In this cohort profile article we describe the lifetime major depressive disorder (MDD) database that has been established as part of the BIObanks Netherlands Internet Collaboration (BIONIC). Across the Netherlands we collected data on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) lifetime MDD diagnosis in 132,850 Dutch individuals. Currently, N = 66,684 of these also have genomewide single nucleotide polymorphism (SNP) data. We initiated this project because the complex genetic basis of MDD requires large population-wide studies with uniform in-depth phenotyping. For standardized phenotyping we developed the LIDAS (LIfetime Depression Assessment Survey), which then was used to measure MDD in 11 Dutch cohorts. Data from these cohorts were combined with diagnostic interview depression data from 5 clinical cohorts to create a dataset of N = 29,650 lifetime MDD cases (22%) meeting DSM-5 criteria and 94,300 screened controls. In addition, genomewide genotype data from the cohorts were assembled into a genomewide association study (GWAS) dataset of N = 66,684 Dutch individuals (25.3% cases). Phenotype data include DSM-5-based MDD diagnoses, sociodemographic variables, information on lifestyle and BMI, characteristics of depressive symptoms and episodes, and psychiatric diagnosis and treatment history. We describe the establishment and harmonization of the BIONIC phenotype and GWAS datasets and provide an overview of the available information and sample characteristics. Our next step is the GWAS of lifetime MDD in the Netherlands, with future plans including fine-grained genetic analyses of depression characteristics, international collaborations and multi-omics studies.

Explanatory and modifying factors of the association between sex and depression onset during adolescence: An exploratory study.

BACKGROUND: The prevalence of Major Depressive Disorder (MDD) is twice as high in women as in men and this difference already emerges during adolescence. Because the mechanisms underlying this sex-difference remain poorly understood, we took a bottom-up approach to identify factors explaining the sex-MDD relationship. METHODS: Data came from the TRacking Adolescents' Individual Lives Survey (TRAILS), a population study investigating youths' development from age 11 into adulthood. We assessed multiple baseline covariates (e.g., demographic, social and psychological) at ages 11-13 years and MDD onset at ages 19 and 25 years. In regression analyses, each covariate's role in the sex-MDD association as an effect modifier or confounder/explanatory variable was investigated. Replicability was evaluated in an independent sample. RESULTS: The analyses identified no effect-modifiers. Baseline internalizing problems, behavioral inhibition, dizziness, comfort in classroom, physical complaints, attention problems, cooperation, self/effortful control, interpersonal life events and computer use partially explained the association between sex and MDD at age 19. The association between sex and MDD at age 25 was explained by largely the same variables, but also by shyness, acne, antisocial behavior, aggression, affection from peers and time spent shopping. The explanatory roles of internalizing problems, behavioral inhibition, negative events involving gossip/rumors and leisure-time spending (computer-use/shopping) were replicated. LIMITATIONS: Potentially important baseline variables were not included or had low response rates. Gender roles or identification were not considered. Baseline MDD was not adjusted for. CONCLUSION: The sex-MDD association is partially explained by sex differences in symptoms and vulnerability factors already present in early adolescence.

The relationship of school performance with self-control and grit is strongly genetic and weakly causal.

The non-cognitive skills self-control and grit are often considered predictors of school performance, but whether this relationship is causal remains unclear. We investigated the causality of this association using a twin design. Specifically, we evaluated the direct impact of self-control and grit on school performance, while controlling for genetic or environmental influences common to all three traits (i.e., confounding). Teachers of 4891 Dutch 12-year-old twin pairs (of which 3837 were complete pairs) completed a survey about school performance (school grades), self-control (ASEBA self-control scale), and the perseverance aspect of grit. Our analysis aimed to determine the direct impact of self-control and grit on school performance, while simultaneously controlling for genetic or environmental confounding. Establishing the regression relationship corrected for confounding supports the interpretation of the regression relationship as causal. In all analyses, we corrected for sex, rater bias of the teachers, and parental socioeconomic status. Initially, in the standard regression, self-control, and grit explained 28.4% of the school performance variance. However, allowing for genetic confounding (due to genetic pleiotropy) revealed that most of this association could be attributed to genetic influences that the three traits share. In the presence of genetic pleiotropy, the phenotypic regression of school performance on self-control and grit accounted for only 4.4% (i.e., the effect size association with the causal hypothesis). In conclusion, self-control and grit predict school performance primarily due to genetic pleiotropy, with a much smaller causal effect (R2 = 4.4%). This suggests that interventions targeting self-control and grit alone may yield limited improvements in school performance.

Childhood abuse v. neglect and risk for major psychiatric disorders.

BACKGROUND: Childhood maltreatment (CM) is a strong risk factor for psychiatric disorders but serves in its current definitions as an umbrella for various fundamentally different childhood experiences. As first step toward a more refined analysis of the impact of CM, our objective is to revisit the relation of abuse and neglect, major subtypes of CM, with symptoms across disorders. METHODS: Three longitudinal studies of major depressive disorder (MDD, N = 1240), bipolar disorder (BD, N = 1339), and schizophrenia (SCZ, N = 577), each including controls (N = 881), were analyzed. Multivariate regression models were used to examine the relation between exposure to abuse, neglect, or their combination to the odds for MDD, BD, SCZ, and symptoms across disorders. Bidirectional Mendelian randomization (MR) was used to probe causality, using genetic instruments of abuse and neglect derived from UK Biobank data (N = 143 473). RESULTS: Abuse was the stronger risk factor for SCZ (OR 3.51, 95% CI 2.17-5.67) and neglect for BD (OR 2.69, 95% CI 2.09-3.46). Combined CM was related to increased risk exceeding additive effects of abuse and neglect for MDD (RERI = 1.4) and BD (RERI = 1.1). Across disorders, abuse was associated with hallucinations (OR 2.16, 95% CI 1.55-3.01) and suicide attempts (OR 2.16, 95% CI 1.55-3.01) whereas neglect was associated with agitation (OR 1.24, 95% CI 1.02-1.51) and reduced need for sleep (OR 1.64, 95% CI 1.08-2.48). MR analyses were consistent with a bidirectional causal effect of abuse with SCZ (IVWforward = 0.13, 95% CI 0.01-0.24). CONCLUSIONS: Childhood abuse and neglect are associated with different risks to psychiatric symptoms and disorders. Unraveling the origin of these differences may advance understanding of disease etiology and ultimately facilitate development of improved personalized treatment strategies.

Relating stability of individual dynamical networks to change in psychopathology.

One hypothesis flowing from the network theory of psychopathology is that symptom network structure is associated with psychopathology severity and in turn, one may expect that individual network structure changes with the level of psychopathology severity. However, this expectation has rarely been addressed directly. This study aims to examine (1) the stability of individual contemporaneous symptom networks over a one-year period and (2) whether network stability is associated with a change in psychopathology. We used daily diary data of n = 66 individuals, located along the psychosis severity continuum, from two separate 90-day periods, one year apart (t = 180). Based on the newly developed Individual Network Invariance Test (INIT) to assess symptom-network stability, participants were divided into two groups with stable and unstable networks and we tested whether these groups differed in their absolute change in psychopathology severity. The majority of the sample (n = 51, 77.3%) showed a stable network over time while most individuals showed a decrease in psychopathological severity. We found no significant association between a change in psychopathology severity and individual network stability. Our results call for further critical evaluation of the association between networks and psychopathology to optimize the implementation of clinical applications based on current methods.

Disentangling the interplay between genes, cognitive skills, and educational level in adolescent and young adult smoking - The TRAILS study.

Recent studies suggest that smoking and lower educational attainment may have genetic influences in common. However, little is known about the mechanisms through which genetics contributes to educational inequalities in adolescent and young adult smoking. Common genetic liabilities may underlie cognitive skills associated with both smoking and education, such as IQ and effortful control, in line with indirect health-related selection explanations. Additionally, by affecting cognitive skills, genes may predict educational trajectories and hereby adolescents' social context, which may be associated with smoking, consistent with social causation explanations. Using data from the Dutch TRAILS Study (N = 1581), we estimated the extent to which polygenic scores (PGSs) for ever smoking regularly (PGSSMOK) and years of education (PGSEDU) predict IQ and effortful control, measured around age 11, and whether these cognitive skills then act as shared predictors of smoking and educational level around age 16, 19, 22, and 26. Second, we assessed if educational level mediated associations between PGSs and smoking. Both PGSs were associated with lower effortful control, and PGSEDU also with lower IQ. Lower IQ and effortful control, in turn, predicted having a lower educational level. However, neither of these cognitive skills were directly associated with smoking behaviour after controlling for covariates and PGSs. This suggests that IQ and effortful control are not shared predictors of smoking and education (i.e., no indirect health-related selection related to cognitive skills). Instead, PGSSMOK and PGSEDU, partly through their associations with lower cognitive skills, predicted selection into a lower educational track, which in turn was associated with more smoking, in line with social causation explanations. Our findings suggest that educational differences in the social context contribute to associations between genetic liabilities and educational inequalities in smoking.

Effect of Daily Life Reward Loop Functioning on the Course of Depression.

Engagement in activities increases positive affect (Reward Path 1), which subsequently reinforces motivation (Reward Path 2), and hence future engagement in activities (Reward Path 3). Strong connections between these three reward loop components are considered adaptive, and might be disturbed in depression. Although some ecological nomentary assessment (EMA) studies have investigated the cross-sectional association between separate reward paths and individuals' level of depression, no EMA study has looked into the association between individuals' reward loop strength and depressive symptom course. The present EMA study assessed reward loop functioning (5x/day, 28 days) of 46 outpatients starting depression treatment at secondary mental health services and monitored with the Inventory of Depressive Symptomatology-Self-Report (IDS-SR) during a 7-month period. Results of multilevel regression analyses showed significant within-person associations for Reward Path 1 (b = 0.21, p < .001), Reward Path 2 (b = 0.43, p < .001), and Reward Path 3 (b = 0.20, p < .001). Stronger average reward loops (i.e., within-person mean of all reward paths) did not relate to participants' improvement in depressive symptoms over time. Path-specific results revealed that Reward Paths 1 and 2 may have partly opposite effects on depressive symptom course. Together, our findings suggest that reward processes in daily life might be best studied separately and that further investigation is warranted to explore under what circumstances strong paths are adaptive or not.

Genetic confounding in bullying research: Causal claims revisited.

Bullying research has shown repeatedly that victims of bullying have an increased risk for later internalizing problems and bullies have an increased risk for later externalizing problems. Bullying involvement is often, either explicitly or implicitly, presented as part of a causal mechanism for maladjustment. However, genetic vulnerability may confound the reported associations. This study examined to what extent genetic vulnerability can account for the reported associations between bullying involvement (age 11-14) and later internalizing and externalizing problems (age 16), using data from the TRacking Adolescents' Individual Lives Survey (n = 1604). Because polygenic scores capture only a fraction of the total genetic effect, they were extrapolated to the size of single-nucleotide polymorphism and twin heritability estimates to examine genetic confounding while controlling for (hypothetical) polygenic scores that fully capture the genetic effect. Genetic vulnerability for internalizing and externalizing problems confounded, respectively, the association between bullying victimization and later internalizing problems, and the association between bullying perpetration and later externalizing problems. As such, this study showcases a method that can be broadly used to assess the magnitude of genetic confounding. Caution is, however, warranted in interpreting particularly the less straightforward extrapolations of polygenic scores to the size of twin heritability estimates.

Direct and indirect associations between childhood adversity and emotional and behavioral problems at age 14: A network analytical approach.

We applied network analysis combined with community detection algorithms to examine how adverse experiences (AEs) (e.g., abuse, bullying victimization, financial difficulties) are, individually and conjunctively, associated with emotional and behavioral problems at age fourteen in the Dutch TRacking Adolescents' Individual Lives Survey (TRAILS, N = 1880, 52.2% female). We found that bullying victimization, peer rejection, parental mental health problems, emotional abuse, and sexual abuse were the only AEs directly contributing to risk of emotional problems. Parental divorce and emotional abuse were the only AEs directly contributing to risk of behavioral problems. Most AEs (e.g., parental employment, parental physical illness) were not conditionally associated with emotional and behavioral problems but may nevertheless contribute to emotional and behavioral problems via associations with other AEs (e.g., parental unemployment and emotional abuse). Community detection algorithms suggested that many of the AEs cluster together (e.g., physical abuse, emotional abuse, and sexual abuse; financial difficulties and parental unemployment), sometimes with emotional and behavioral problems (e.g., bullying victimization, peer rejection and emotional problems). Our findings shed light on how individual AEs contribute to risks of emotional and behavioral problems directly, and indirectly through associations with other AEs.

ADHD Symptoms and Educational Level in Adolescents: The Role of the Family, Teachers, and Peers.

Few studies have explored the contribution of family and school factors to the association between ADHD symptoms and lower education. Possibly, having more ADHD symptoms contributes to poorer family functioning and less social support, and consequently a lower educational level (i.e., mediation). Moreover, the negative effects of ADHD symptoms on education may be stronger for adolescents with poorer family functioning or less social support (i.e., interaction). Using data of the Dutch TRAILS Study (N = 2,229), we evaluated associations between ADHD symptoms around age 11 and educational level around age 14, as well as between ADHD symptoms around age 14 and 16 years and subsequent changes in educational level around age 16 and 19, respectively. We assessed the potential mediating role of family functioning, and social support by teachers and classmates, all measured around ages 11, 14, and 16, while additionally evaluating interactions between ADHD symptoms and these hypothesized mediators. ADHD symptoms were associated with poorer family functioning, less social support by teachers and classmates, and lower education throughout adolescence. No conclusive evidence of mediation was found, because unique associations between family functioning and social support by teachers and classmates and education were largely absent. Furthermore, we found no interactions between ADHD symptoms and family functioning and social support by teachers and classmates. Although social support by teachers and classmates and good family functioning may benefit the wellbeing and mental health of adolescents with high levels of ADHD symptoms, they will not necessarily improve their educational attainment.

Associations between type of childhood adversities and labour market participation and employment conditions in young adults.

BACKGROUND: Cumulative exposure to childhood adversity is associated with a variety of labour market outcomes in young adulthood. It remains largely unclear whether the type of adversity matters in this association. This prospective study examined the differences in exposure to 14 adverse experiences among groups of young adults aged 22 characterised by distinct labour market participation states and employment conditions. METHODS: We used data from the TRacking Adolescents' Individual Lives Survey, a Dutch prospective cohort study with 15 years of follow-up (N=1524). We included 14 adverse experiences (ages 0-16) across five domains: peer influences, loss or threat of loss, material deprivation, family dynamics and maltreatment. Labour market participation states and employment conditions were assessed at age 22. We used latent class analysis to derive labour market outcome groups, which we subsequently compared on exposure to adverse experiences using pairwise comparisons. RESULTS: Inactive individuals (n=85, 5.6%), often neither in education (77.4%) nor employment (98.6%) and on benefits (94.4%), were more likely to be exposed to many distinct types of adverse experiences (eg, parental addiction, bullying victimisation) as compared with all other groups. Early workers (n=413, 27.1%), often on temporary contracts and low monthly incomes, were more likely to be exposed to parental divorce (22.7%) compared with students with side jobs (12.9%). CONCLUSIONS: Different adverse experiences are not equally associated with labour market outcomes. Researchers and stakeholders in policy and practice should be aware of the differences between adverse experiences in their importance for labour market outcomes in young adults.

Annual Research Review: Stability of psychopathology: lessons learned from longitudinal population surveys.

BACKGROUND: Psychopathology has been long recognized as a fluctuating process with various expressions over time, which can only be properly understood if we follow individuals and their social context from childhood up until adulthood. Longitudinal population-based studies have yielded powerful data to analyze this process. However, the resulting publications have not been reflected upon with regard to (a) the homotypic and heterotypic stability of internalizing and externalizing problems and (b) how transactions between psychopathology and environmental factors shape its development. METHODS: In this narrative review, we primarily focused on population-based studies that followed cohorts repeatedly from an early age (<18 years) onwards, across multiple stages of development, using statistical methods that permit inferences about within-person bidirectional associations between internalizing and externalizing problems or psychopathology-environment transactions. RESULTS: There is robust evidence that mental health problems in childhood or adolescence predict psychiatric problems later in development. In terms of the broadband domains internalizing and externalizing problems, homotypic stability greatly exceeds heterotypic stability and transitions from purely internalizing to purely externalizing problems or vice versa are rare. Homotypic rank-order stabilities seem to increase over time. Findings regarding transactions with environmental factors are less robust, due to widely varying research topics and designs, and a scarcity of studies that separated between-person differences from within-person changes. In general, however, the literature shows little consistent evidence for substantial mutual prospective influences between psychopathology and environmental factors. CONCLUSIONS: Longitudinal surveys have strongly augmented insight into homotypic and heterotypic stability and change. Attempts to unravel the myriad of risk and protective factors that place individuals on particular pathways or deflect them from these pathways are still in a pioneering phase and have not yet generated robust findings. As a way forward, we propose to join forces and develop a common risk factor taxonomy.

Sociodemographic, lifestyle and clinical characteristics of energy-related depression symptoms: A pooled analysis of 13,965 depressed cases in 8 Dutch cohorts.

BACKGROUND: In a substantial subgroup of depressed patients, atypical, energy-related depression symptoms (e.g. increased appetite/weight, hypersomnia, loss of energy) tend to cluster with immuno-metabolic dysregulations (e.g. increased BMI and inflammatory markers). This clustering is proposed to reflect a more homogeneous depression pathology. This study examines to what extent energy-related symptoms are associated and share sociodemographic, lifestyle and clinical characteristics. METHODS: Data were available from 13,965 participants from eight Dutch cohorts with DSM-5 lifetime major depression assessed by the Lifetime Depression Assessment Self-report (LIDAS) questionnaire. Information on four energy-related depression symptoms were extracted: energy loss, increased appetite, increased weight, and hypersomnia. Tetrachoric correlations between these symptoms, and associations of these symptoms with sociodemographic (sex, age, education), lifestyle (physical activity, BMI, smoking) and clinical characteristics (age of onset, episode duration, history, treatment and recency, and self-reported comorbidity) were computed. RESULTS: Correlations between energy-related symptoms were overall higher than those with other depression symptoms and varied from 0.90 (increased appetite vs increased weight) to 0.11 (increased appetite vs energy loss). All energy-related symptoms were strongly associated with higher BMI and a more severe clinical profile. Patients with increased appetite were more often smokers, and only patients with increased appetite or weight more often had a self-reported diagnosis of PTSD (OR = 1.17, p = 2.91E-08) and eating disorder (OR = 1.40, p = 4.08E-17). CONCLUSIONS: The symptom-specific associations may have consequences for a profile integrating these symptoms, which can be used to reflect immuno-metabolic depression. They indicate the need to study immuno-metabolic depression at individual symptom resolution as a starting point.

Educational level, attention problems, and externalizing behaviour in adolescence and early adulthood: the role of social causation and health-related selection-the TRAILS study.

Social causation and health-related selection may contribute to educational differences in adolescents' attention problems and externalizing behaviour. The social causation hypothesis posits that the social environment influences adolescents' mental health. Conversely, the health-related selection hypothesis proposes that poor mental health predicts lower educational attainment. From past studies it is unclear which of these mechanisms predominates, as attention problems and externalizing behaviour have the potential to interfere with educational attainment, but may also be affected by differences in the educational context. Furthermore, educational gradients in mental health may reflect the impact of 'third variables' already present in childhood, such as parental socioeconomic status (SES), and IQ. We investigated both hypotheses in relation to educational differences in externalizing behaviour and attention problems throughout adolescence and young adulthood. We used data from a Dutch cohort (TRAILS Study; n = 2229), including five measurements of educational level, externalizing behaviour, and attention problems from around age 14-26 years. First, we evaluated the directionality in longitudinal associations between education, externalizing behaviour, and attention problems with and without adjusting for individual differences using fixed effects. Second, we assessed the role of IQ and parental SES in relation to attention problems, externalizing behaviour, and educational level. Attention problems predicted decreases in education throughout all of adolescence and young adulthood. Differences in parental SES contributed to increases in externalizing behaviour amongst the lower educational tracks in mid-adolescence. Childhood IQ and parental SES strongly predicted education around age 14. Parental SES, but not IQ, also predicted early adolescent attention problems and externalizing behaviour. Our results provide support for the health-related selection hypothesis in relation to attention problems and educational attainment. Further, our results highlight the role of social causation from parental SES in determining adolescent educational level, attention problems, and externalizing behaviour.

Relationship Between Childhood Abuse and Body Mass Index in Young Adulthood: Mediated by Depression and Anxiety?

We examined whether childhood abuse is related to body mass index (BMI) in young adults and whether this relationship is mediated by depression and anxiety. Data are from the Dutch longitudinal cohort study TRAILS (nfemales = 836, nmales = 719). At wave 4, childhood sexual, physical and verbal abuse, and lifetime major depressive disorder (MDD) and generalized anxiety disorder (GAD) were assessed. BMI was measured at wave 4 and 5 (mean age = 19.2/22.4 years). Sex-stratified structural equation models were estimated. Females who had experienced sexual abuse had a higher BMI at wave 4 (B = 0.97, 95%CI = [-0.01,1.96]) and a higher increase in BMI between wave 4 and 5 (B = 0.52, 95%CI = [0.04,1.01]) than females who had not experienced sexual abuse. Additionally, MDD and BMI at wave 4 were related in females (B = 1.35, 95%CI = [0.52,2.18]). MDD mediated the relationship between sexual abuse and BMI at wave 4 in females. In addition, sexual abuse moderated the relationship between MDD and BMI at wave 4. The relationship was stronger among females who had experienced sexual abuse than among females who had not. Prevention of BMI changes among females who experienced sexual abuse may thus be warranted, particularly when they developed MDD. MDD treatment, such as abuse-focused psychotherapy, may aid this prevention.

Uncovering the genetic architecture of broad antisocial behavior through a genome-wide association study meta-analysis.

Despite the substantial heritability of antisocial behavior (ASB), specific genetic variants robustly associated with the trait have not been identified. The present study by the Broad Antisocial Behavior Consortium (BroadABC) meta-analyzed data from 28 discovery samples (N = 85,359) and five independent replication samples (N = 8058) with genotypic data and broad measures of ASB. We identified the first significant genetic associations with broad ASB, involving common intronic variants in the forkhead box protein P2 (FOXP2) gene (lead SNP rs12536335, p = 6.32 × 10-10). Furthermore, we observed intronic variation in Foxp2 and one of its targets (Cntnap2) distinguishing a mouse model of pathological aggression (BALB/cJ strain) from controls (BALB/cByJ strain). Polygenic risk score (PRS) analyses in independent samples revealed that the genetic risk for ASB was associated with several antisocial outcomes across the lifespan, including diagnosis of conduct disorder, official criminal convictions, and trajectories of antisocial development. We found substantial genetic correlations of ASB with mental health (depression rg = 0.63, insomnia rg = 0.47), physical health (overweight rg = 0.19, waist-to-hip ratio rg = 0.32), smoking (rg = 0.54), cognitive ability (intelligence rg = -0.40), educational attainment (years of schooling rg = -0.46) and reproductive traits (age at first birth rg = -0.58, father's age at death rg = -0.54). Our findings provide a starting point toward identifying critical biosocial risk mechanisms for the development of ASB.

A genome-wide association study of total child psychiatric problems scores.

Substantial genetic correlations have been reported across psychiatric disorders and numerous cross-disorder genetic variants have been detected. To identify the genetic variants underlying general psychopathology in childhood, we performed a genome-wide association study using a total psychiatric problem score. We analyzed 6,844,199 common SNPs in 38,418 school-aged children from 20 population-based cohorts participating in the EAGLE consortium. The SNP heritability of total psychiatric problems was 5.4% (SE = 0.01) and two loci reached genome-wide significance: rs10767094 and rs202005905. We also observed an association of SBF2, a gene associated with neuroticism in previous GWAS, with total psychiatric problems. The genetic effects underlying the total score were shared with common psychiatric disorders only (attention-deficit/hyperactivity disorder, anxiety, depression, insomnia) (rG > 0.49), but not with autism or the less common adult disorders (schizophrenia, bipolar disorder, or eating disorders) (rG < 0.01). Importantly, the total psychiatric problem score also showed at least a moderate genetic correlation with intelligence, educational attainment, wellbeing, smoking, and body fat (rG > 0.29). The results suggest that many common genetic variants are associated with childhood psychiatric symptoms and related phenotypes in general instead of with specific symptoms. Further research is needed to establish causality and pleiotropic mechanisms between related traits.

Socioeconomic inequalities in adolescent health behaviours across 32 different countries - The role of country-level social mobility.

Higher family affluence is associated with healthier behaviours in adolescents, but the strength of this association varies across countries. Differences in social mobility at the country-level, i.e. the extent to which adolescents develop a different socioeconomic status (SES) than their parents, may partially explain why the association between family affluence and adolescent health behaviours is stronger in some countries than in others. Using data from adolescents aged 11-15 years from 32 countries, participating in the 2017/2018 wave of the Health Behaviour in School-aged Children (HBSC) study (N = 185,086), we employed multilevel regression models with cross-level interactions to examine whether country-level social mobility moderates the association between family affluence and adolescent health behaviours (i.e. moderate-to-vigorous physical activity, vigorous physical activity, healthy and unhealthy foods consumption, having breakfast regularly, and weekly smoking). Higher family affluence was more strongly associated with higher levels of adolescent physical activity in countries characterized by high levels of social mobility. No cross-level interactions were found for any of the other health behaviours. Differences in social mobility at the country-level may contribute to cross-national variations in socioeconomic inequalities in adolescent physical activity. Further research can shed light on the mechanisms linking country-level social mobility to inequalities in adolescent physical activity to identify targets for policy and interventions.