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The present study examined patterns of stability and change in loneliness across adolescence. Data were drawn from the Environmental Risk (E-Risk) Longitudinal Twin Study, a UK population-representative cohort of 2,232 individuals born in 1994 and 1995. Loneliness was assessed when participants were aged 12 and 18. Loneliness showed modest stability across these ages (r = .25). Behavioral genetic modeling indicated that stability in loneliness was explained largely by genetic influences (66%), while change was explained by nonshared environmental effects (58%). Individuals who reported loneliness at both ages were broadly similar to individuals who only reported it at age 18, with both groups at elevated risk of mental health problems, physical health risk behaviors, and education and employment difficulties. Individuals who were lonely only at age 12 generally fared better; however, they were still more likely to finish school with lower qualifications. Positive family influences in childhood predicted reduced risk of loneliness at age 12, while negative peer experiences increased the risk. Together, the findings show that while early adolescent loneliness does not appear to exert a cumulative burden when it persists, it is nonetheless a risk for a range of concomitant impairments, some of which can endure.

Background and Hypothesis Children exposed to socioenvironmental adversities (eg, urbanicity, pollution, neighborhood deprivation, crime, and family disadvantage) are more likely to subsequently develop subclinical psychotic experiences during adolescence (eg, hearing voices, paranoia). However, the pathways through which this occurs have not been previously investigated. We hypothesized that cognitive ability and inflammation would partly explain this association. Study Design Data were utilized from the Environmental-Risk Longitudinal Twin Study, a cohort of 2232 children born in 1994–1995 in England and Wales and followed to age 18. Socioenvironmental adversities were measured from birth to age 10 and classified into physical risk (defined by high urbanicity and air pollution) and socioeconomic risk (defined by high neighborhood deprivation, neighborhood disorder, and family disadvantage). Cognitive abilities (overall, crystallized, fluid, and working memory) were assessed at age 12; and inflammatory markers (C-reactive protein, interleukin-6, soluble urokinase plasminogen activator receptor) were measured at age 18 from blood samples. Participants were interviewed at age 18 regarding psychotic experiences. Study Results Higher physical risk and socioeconomic risk were associated with increased odds of psychotic experiences in adolescence. The largest mediation pathways were from socioeconomic risk via overall cognitive ability and crystallized ability, which accounted for ~11% and ~19% of the association with psychotic experiences, respectively. No statistically significant pathways were found via inflammatory markers in exploratory (partially cross-sectional) analyses. Conclusions Cognitive ability, especially crystallized ability, may partly explain the association between childhood socioenvironmental adversity and adolescent psychotic experiences. Interventions to support cognitive development among children living in disadvantaged settings could buffer them against developing subclinical psychotic phenomena.

Study Objectives Digital technology use is associated with poor sleep quality in adolescence and young adulthood although research findings have been mixed. No studies have addressed the association between the two using a genetically informative twin design which could extend our understanding of the etiology of this relationship. This study aimed to test: (1) the association between adolescents’ perceived problematic use of digital technology and poor sleep quality, (2) whether the association between problematic use of technology and poor sleep quality remains after controlling for familial factors, and (3) genetic and environmental influences on the association between problematic use of technology and poor sleep quality. Methods Participants were 2232 study members (18-year-old twins) of the Environmental Risk (E-Risk) Longitudinal Twin Study. The sample was 48.9% male, 90% white, and 55.6% monozygotic. We conducted regression and twin difference analyses and fitted twin models. Results Twin differences for problematic use of technology were associated with differences for poor sleep quality in the whole sample (p < 0.001; B = 0.15) and also when we limited the analyses to identical twins only (p < 0.001; B = 0.21). We observed a substantial genetic correlation between problematic use of technology and sleep quality (rA = 0.31), whereas the environmental correlation was lower (rE = 0.16). Conclusions Adolescent reported problematic use of digital technology is associated with poor sleep quality—even after controlling for familial factors including genetic confounds. Our results suggest that the association between adolescents’ sleep and problematic digital technology use is not accounted for by shared genetic liability or familial factors but could reflect a causal association. This robust association needs to be examined in future research designed to test causal associations.

Background Trajectories of attention-deficit hyperactivity disorder (ADHD) traits spanning early childhood to mid-life have not been described in general populations across different geographical contexts. Population trajectories are crucial to better understanding typical developmental patterns. Methods We combined repeated assessments of ADHD traits from five population-based cohorts, spanning ages 3 to 45 years. We used two measures: (i) the Strengths and Difficulties Questionnaire (SDQ) hyperactive-inattentive subscale (175 831 observations, 29 519 individuals); and (ii) scores from DSM-referenced scales (118 144 observations, 28 685 individuals). Multilevel linear spline models allowed for non-linear change over time and differences between cohorts and raters (parent/teacher/self). Results Patterns of age-related change differed by measure, cohort and country: overall, SDQ scores decreased with age, most rapidly declining before age 8 years (-0.157, 95% CI: -0.170, -0.144 per year). The pattern was generally consistent using DSM scores, although with greater between-cohort variation. DSM scores decreased most rapidly between ages 14 and 17 years (-1.32%, 95% CI: -1.471, -1.170 per year). Average scores were consistently lower for females than males (SDQ: -0.818, 95% CI: -0.856, -0.780; DSM: -4.934%, 95% CI: -5.378, -4.489). This sex difference decreased over age for both measures, due to an overall steeper decrease for males. Conclusions ADHD trait scores declined from childhood to mid-life, with marked variation between cohorts. Our results highlight the importance of taking a developmental perspective when considering typical population traits. When interpreting changes in clinical cohorts, it is important to consider the pattern of expected change within the general population, which is influenced by cultural context and measurement.

Objective: We investigated whether “late-onset” ADHD that emerges in adolescence/adulthood is similar in risk factor profile to: (1) child-onset ADHD, but emerges later because of scaffolding/compensation from childhood resources; and (2) depression, because it typically onsets in adolescence/adulthood and shows symptom and genetic overlaps with ADHD. Methods: We examined associations between late-onset ADHD and ADHD risk factors, cognitive tasks, childhood resources and depression risk factors in a population-based cohort followed-up to age 25 years ( N=4224–9764). Results: Parent-rated late-onset ADHD was like child-onset persistent ADHD in associations with ADHD polygenic risk scores and cognitive task performance, although self-rated late-onset ADHD was not. Late-onset ADHD was associated with higher levels of childhood resources than child-onset ADHD and did not show strong evidence of association with depression risk factors. Conclusions: Late-onset ADHD shares characteristics with child-onset ADHD when parent-rated, but differences for self-reports require investigation. Childhood resources may delay the onset of ADHD.

The environment and events that we are exposed to in utero, during birth and in early childhood influence our future physical and mental health. The underlying mechanisms that lead to these outcomes are unclear, but long-term changes in epigenetic marks, such as DNA methylation, could act as a mediating factor or biomarker. DNA methylation data were assayed at 713 522 CpG sites from 9537 participants of the Generation Scotland: Scottish Family Health Study, a family-based cohort with extensive genetic, medical, family history and lifestyle information. Methylome-wide association studies of eight early life environment phenotypes and two adult mental health phenotypes (major depressive disorder and brief resilience scale) were conducted using DNA methylation data collected from adult whole blood samples. Two genes involved with different developmental pathways (PRICKLE2, Prickle Planar Cell Polarity Protein 2 and ABI1, Abl-Interactor-1) were annotated to CpG sites associated with preterm birth (P

OBJECTIVE: To understand whether genetic risk for attention-deficit/hyperactivity disorder (ADHD) is associated with the course of the disorder across childhood and into young adulthood.METHOD: Participants were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a population-based birth cohort of 2,232 twins. ADHD was assessed at ages 5, 7, 10, and 12 with mother- and teacher-reports and at age 18 with self-report. Polygenic risk scores (PRSs) were created using a genome-wide association study of ADHD case status. Associations with PRS were examined at multiple points in childhood and longitudinally from early childhood to adolescence. We investigated ADHD PRS and course to young adulthood, as reflected by ADHD remission, persistence, and late onset.RESULTS: Participants with higher ADHD PRSs had increased risk for meeting ADHD diagnostic criteria (odds ratios ranging from 1.17 at age 10 to 1.54 at age 12) and for elevated symptoms at ages 5, 7, 10, and 12. Higher PRS was longitudinally associated with more hyperactivity/impulsivity (incidence rate ratio = 1.18) and inattention (incidence rate ratio = 1.14) from age 5 to age 12. In young adulthood, participants with persistent ADHD exhibited the highest PRS (mean PRS = 0.37), followed by participants with remission (mean PRS = 0.21); both groups had higher PRS than controls (mean PRS = -0.03), but did not significantly differ from one another. Participants with late-onset ADHD did not show elevated PRS for ADHD, depression, alcohol dependence, or marijuana use disorder.CONCLUSION: Genetic risk scores derived from case-control genome-wide association studies may have relevance not only for incidence of mental health disorders, but also for understanding the longitudinal course of mental health disorders.

The present study used quantitative and qualitative methods to explore how lonely young people are seen from others’ perspectives, in terms of their personality, behavior, and life circumstances. Data were drawn from the Environmental Risk Longitudinal Twin Study, a cohort of 2,232 individuals born in the U.K. in the mid-1990s. When participants were aged 18, they provided self-reports of loneliness, and informant ratings of loneliness were provided by interviewers, as well as participants’ parents and siblings. Interviewers further provided Big Five personality ratings and detailed written notes in which they documented their perceptions of the participants and their reflections on the content of the interview. In the quantitative section of the article, regression analyses were used to examine the perceptibility of loneliness and how participants’ loneliness related to their perceived personality traits. The informant ratings of participants’ loneliness showed good agreement with self-reports. Furthermore, loneliness was associated with lower perceived conscientiousness, agreeableness, and extroversion and higher perceived neuroticism. Within-twin pair analyses indicated that these associations were partly explained by common underlying genetic influences. In the qualitative section of the study, the loneliest 5% of study participants ( N = 108) were selected, and thematic analysis was applied to the study interviewers’ notes about those participants. Three themes were identified and named: “uncomfortable in own skin,” “clustering of risk,” and “difficulties accessing social resources.” These results add depth to the current conceptualization of loneliness and emphasize the complexity and intersectional nature of the circumstances severely lonely young adults live in.

Little is known about the genetic architecture of traits affecting educational attainment other than cognitive ability. We used Genomic Structural Equation Modeling and prior genome-wide association studies (GWAS) of educational attainment (n = 1,131,881) and cognitive test performance (n = 257,841) to estimate SNP associations with educational attainment variation that is independent of cognitive ability.We identified 157 genome-wide significant loci and a polygenic architecture accounting for 57% of genetic variance in educational attainment. Non-cognitive genetics were enriched in the same brain tissues and cell types as cognitive performance but showed different associations with gray-matter brain volumes. Non-cognitive genetics were further distinguished by associations with personality traits, less risky behavior,and increased risk for certain psychiatric disorders.For socioeconomic success and longevity, non-cognitive and cognitive-performance genetics demonstrated similar-magnitude associations. By conducting a GWAS of a phenotype that was not directly measured, we offer a first view of genetic architecture of non-cognitive skills influencing educational success.

Objective Prediction models have become frequent in the medical literature, but most published studies are conducted in a single setting. Heterogeneity between development and validation samples has been posited as a major obstacle for the generalization of models. We aimed to develop a multivariable prognostic model using sociodemographic variables easily obtainable from adolescents at age 15 to predict a depressive disorder diagnosis at age 18, and to evaluate its generalizability in two samples from diverse socioeconomic and cultural settings. Method Data from the 1993 Pelotas Birth Cohort were used to develop the prediction model, and its generalizability was evaluated in two representative cohort studies: the Environmental Risk (E-Risk) Longitudinal Twin Study and the Dunedin Multidisciplinary Health and Development Study. Results At age 15, 2,192 adolescents with no evidence of current or previous depression were included (44.6% male). The apparent C-statistic of the models derived in Pelotas ranged from 0.76 to 0.79, and the model obtained from a penalized logistic regression was selected for subsequent external evaluation. Major discrepancies between the samples were identified, impacting the external prognostic performance of the model (Dunedin and E-Risk C-statistics of 0.63 and 0.59, respectively). The implementation of recommended strategies to account for this heterogeneity among samples improved the model’s calibration in both samples. Conclusion An adolescent depression risk score comprising easily obtainable predictors was developed with good prognostic performance in a Brazilian sample. Heterogeneity among settings was not trivial, but strategies to deal with sample diversity were identified as pivotal for providing better risk stratification across samples. Future efforts should focus on developing better methodological approaches for incorporating heterogeneity in prognostic research.

Accumulating evidence suggests that individuals exposed to victimization at key developmental stages may have different epigenetic fingerprints compared to those exposed to no/minimal stressful events, however results are inconclusive. This study aimed to strengthen causal inference regarding the impact of adolescent victimization on the epigenome by controlling for genetic variation, age, gender, and shared environmental exposures. We conducted longitudinal epigenome-wide association analyses (EWAS) on DNA methylation (DNAm) profiles of 118 monozygotic (MZ) twin pairs from the Environmental Risk study with and without severe adolescent victimization generated using buccal DNA collected at ages 5, 10 and 18, and the Illumina EPIC array. Additionally, we performed cross-sectional EWAS on age-18 blood and buccal DNA from the same individuals to elucidate tissue-specific signatures of severe adolescent victimization. Our analyses identified 20 suggestive differentially methylated positions (DMPs) (P

Background Bullying victimisation has been associated with increased risk of suicide ideation and attempt throughout the lifespan, but no study has yet examined whether it translates to a greater risk of death by suicide. We aimed to determine the association of bullying victimisation with suicide mortality. Methods Participants were drawn from the 1958 British birth cohort, a prospective follow-up of all births in 1 week in Britain in 1958. We conducted logistic regressions on 14 946 participants whose mothers reported bullying victimisation at 7 and 11 years with linked information on suicide deaths through the National Health Service Central Register. Results Fifty-five participants (48 males) had died by suicide between the age 18 and 52 years. Bullying victimisation was associated with suicide mortality; a one standard deviation increases in bullying victimisation linked to an increased odds for suicide mortality [odds ratio (OR) 1.29; 1.02–1.64] during adulthood. The OR attenuated by 11% after adjustment for individual (e.g. behavioural and emotional problems) and familial characteristics (e.g. adverse childhood experiences, 1.18; 0.92–1.51). Analysis of bullying victimisation frequency categories yields similar results: compared with individuals who had not been bullied, those who had been frequently bullied had an increased odds for suicide mortality (OR 1.89; 0.99–3.62). Conclusion Our study suggests that individuals who have been frequently bullied have a small increased risk of dying by suicide, when no other risk factors is considered. Suicide prevention might start in childhood, with bullying included in a range of inter-correlated vulnerabilities encompassing behavioural and emotional difficulties and adverse experiences within the family.

The present study used a longitudinal and discordant twin design to explore in depth the developmental associations between victimization and loneliness from mid-childhood to young adulthood. The data were drawn from the Environmental Risk (E-Risk) Longitudinal Twin Study, a birth cohort of 2,232 individuals born in England and Wales during 1994–1995. Diverse forms of victimization were considered, differing across context, perpetrator, and timing of exposure. The results indicated that exposure to different forms of victimization was associated with loneliness in a dose–response manner. In childhood, bullying victimization was uniquely associated with loneliness, over and above concurrent psychopathology, social isolation, and genetic risk. Moreover, childhood bullying victimization continued to predict loneliness in young adulthood, even in the absence of ongoing victimization. Within-twin pair analyses further indicated that this longitudinal association was explained by genetic confounds. In adolescence, varied forms of victimization were correlated with young adult loneliness, with maltreatment, neglect, and cybervictimization remaining robust to controls for genetic confounds. These findings indicate that vulnerability to loneliness in victimized young people varies according to the specific form of victimization in question, and also to the developmental period in which it was experienced.

Objectives: Examine the extent to which cognitive/psychological characteristics predict later polyvictimization. We employ a twin-based design that allows us to test the social neurocriminology hypothesis that environmental factors influence brain-based characteristics and influence behaviors like victimization.Methods: Using data from the Environmental Risk Longitudinal Twin Study (N = 1986), we capitalize on the natural experiment embedded in a discordant-twin design that allows for the adjustment of family environments and genetic factors. Results: The findings indicate that self-control, as well as symptoms of conduct disorder and anxiety, are related to polyvictimization even after adjusting for family environments and partially adjusting for genetic influences. After fully adjusting for genetic factors, only self-control was a statistically significant predictor of polyvictimization.Conclusion: The findings suggest polyvictimization is influenced by cognitive/psychological characteristics that individuals carry with them across contexts. Policies aimed at reducing victimization risks should consider interventions that address cognitive functioning and mental health.

Background: Attention deficit/hyperactivity disorder (ADHD) is associated with emotional problems and their co-occurrence often leads to worse outcomes. We investigated the developmental associations between ADHD and emotional problems from childhood to early adolescence and examined the genetic and environmental contributions to their developmental link. We further tested whether this developmental association remained across the transition to young adulthood. Methods: We used data from the Environmental Risk (E-Risk) Longitudinal Twin Study, a cohort of 2,232 British twins. In childhood, ADHD and emotional problems were assessed at ages 5, 7, 10 and 12 with mothers’ and teachers’ reports. At age 18, we used self-reported symptoms according to DSM-5 criteria for ADHD, and DSM-IV for anxiety and depression. Results: Longitudinal analyses showed that earlier ADHD was associated with later emotional problems consistently across childhood. However, earlier emotional problems were not associated with later ADHD symptoms. The developmental association between ADHD and later emotional problems in childhood was entirely explained by common genetic factors. Consistent with results in childhood, earlier symptoms of ADHD were associated with later emotional problems during the transition to young adulthood. Conclusions: Our findings demonstrate that ADHD symptoms are predictors of the development of emotional problems, from childhood up to young adulthood, through shared genetic influences. Interventions targeting ADHD symptoms might prevent the development of emotional problems. Clinicians treating youth with ADHD must be aware of their risk for developing emotional problems, and ought to assess, monitor, and treat emotional problems alongside ADHD symptoms from childhood to adulthood.

Children from lower-income households are at increased risk for poor health, educational failure, and behavioral problems. This social gradient is one of the most reproduced findings in health and social science. How people view their position in social hierarchies also signals poor health. However, when adolescents’ views of their social position begin to independently relate to well-being is currently unknown. A cotwin design was leveraged to test whether adolescents with identical family backgrounds, but who viewed their family’s social status as higher than their same-aged and sex sibling, experienced better well-being in early and late adolescence. Participants were members of the Environmental Risk Longitudinal Twin Study, a representative cohort of British twins (n = 2,232) followed across the first 2 decades of life. By late adolescence, perceptions of subjective family social status (SFSS) robustly correlated with multiple indicators of health and well-being, including depression; anxiety; conduct problems; marijuana use; optimism; not in education, employment, or training (NEET) status; and crime. Findings held controlling for objective socioeconomic status both statistically and by cotwin design after accounting for measures of childhood intelligence (IQ), negative affect, and prior mental health risk and when self-report, informant report, and administrative data were used. Little support was found for the biological embedding of adolescents’ perceptions of familial social status as indexed by inflammatory biomarkers or cognitive tests in late adolescence or for SFSS in early adolescence as a robust correlate of well-being or predictor of future problems. Future experimental studies are required to test whether altering adolescents’ subjective social status will lead to improved well-being and social mobility.

What impact does formal punishment have on antisocial conduct—does it deter or promote it? The findings from a long line of research on the labeling tradition indicate formal punishments have the opposite‐of‐intended consequence of promoting future misbehavior. In another body of work, the results show support for deterrence‐based hypotheses that punishment deters future misbehavior. So, which is it? We draw on a nationally representative sample of British adolescent twins from the Environmental Risk (E‐Risk) Longitudinal Twin Study to perform a robust test of the deterrence versus labeling question. We leverage a powerful research design in which twins can serve as the counterfactual for their co‐twin, thereby ruling out many sources of confounding that have likely impacted prior studies. The pattern of findings provides support for labeling theory, showing that contact with the justice system—through spending a night in jail/prison, being issued an anti‐social behaviour order (ASBO), or having an official record—promotes delinquency. We conclude by discussing the impact these findings may have on criminologists’ and practitioners’ perspective on the role of the juvenile justice system in society.

Purpose To investigate whether (1) depression is associated with increased risk of past-year intimate partner violence (IPV) perpetration, disaggregated by sex, after controlling for potential confounders; (2) observed associations are mediated by alcohol misuse or past-year IPV victimisation. Methods Systematic review and individual participant data (IPD) meta-mediation analysis of general population surveys of participants aged 16 years or older, that were conducted in a high-income country setting, and measured mental disorder and IPV perpetration in the last 12 months. Results Four datasets contributed to meta-mediation analyses, with a combined sample of 12,679 participants. Depression was associated with a 7.4% and 4.8% proportion increase of past-year physical IPV perpetration among women and men, respectively. We found no evidence of mediation by alcohol misuse. Among women, past-year IPV victimisation mediated 45% of the total effect of depression on past-year IPV perpetration. Past-year severe IPV victimisation mediated 60% of the total effect of depression on past-year severe IPV perpetration. We could not investigate IPV victimisation as a mediator among men due to perfect prediction. Conclusions Mental health services, criminal justice services, and domestic violence perpetrator programmes should be aware that depression is associated with increased risk of IPV perpetration. Interventions to reduce IPV victimisation might help prevent IPV perpetration by women. Data collection on mental disorder and IPV perpetration should be strengthened in future population-based surveys, with greater consistency of data collection across surveys, as only four studies were able to contribute to the meta-mediation analysis.

Purpose Bullying behaviours and other conduct problems often co-occur. However, we do not yet know whether bullying behaviours are associated with early factors and later poor outcomes independently of conduct problems. While there are differing, specific interventions for bullying behaviours and for conduct problems, it is unclear if such specificity is justified given parallels between both behaviours. Methods We used prospective data from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative sample of 2232 children. Mothers and teachers reported on children’s bullying behaviours and conduct problems at ages 7 and 10. We collected measures of risk factors, including temperament and family factors, when children were age 5. We assessed behavioural, emotional, educational and social problems when participants reached the ages of 12 and 18. Results Bullying behaviours and conduct problems co-occurred in childhood. Our findings indicated that bullying behaviours and other conduct problems were independently associated with the same risk factors. Furthermore, they were associated with the same poor outcomes at both ages 12 and 18. Despite this, bullying behaviours were uniquely associated with behavioural, emotional, educational and social problems at age 18. Conclusions Our findings suggest that anti-bullying programmes and interventions aimed at reducing conduct problems could benefit from greater integration. Furthermore, our study highlights the mental health problems children who bully may face in later years and the need to consider those in intervention plans.

BackgroundPeer victimization is associated with a wide range of mental health problems in youth, yet few studies described its association with mental health comorbidities.MethodsTo test the association between peer victimization timing and intensity and mental health comorbidities, we used data from 1216 participants drawn from the Quebec Longitudinal Study of Child Development, a population-based birth cohort. Peer victimization was self-reported at ages 6–17 years, and modeled as four trajectory groups: low, childhood-limited, moderate adolescence-emerging, and high-chronic. The outcomes were the number and the type of co-occurring self-reported mental health problems at age 20 years. Associations were estimated using negative binomial and multinomial logistic regression models and adjusted for parent, family, and child characteristics using propensity score inverse probability weights.ResultsYouth in all peer victimization groups had higher rates of co-occurring mental health problems and higher likelihood of comorbid internalizing-externalizing problems [odds ratios ranged from 2.06, 95% confidence interval (CI) 1.52–2.79 for childhood-limited to 4.34, 95% CI 3.15–5.98 for high-chronic victimization] compared to those in the low victimization group. The strength of these associations was highest for the high-chronic group, followed by moderate adolescence-emerging and childhood-limited groups. All groups also presented higher likelihood of internalizing-only problems relative to the low peer victimization group.ConclusionsIrrespective of timing and intensity, self-reported peer victimization was associated with mental health comorbidities in young adulthood, with the strongest associations observed for high-chronic peer victimization. Tackling peer victimization, especially when persistent over time, could play a role in reducing severe and complex mental health problems in youth.

Inflammation is associated with poor physical and mental health including major depressive disorder (MDD). Moreover, there is evidence that childhood adversity - a risk factor for MDD - becomes biologically embedded via elevated inflammation. However, the risk of developing MDD arises from multiple sources and yet there has been little investigation of the links between individuals' constellation of MDD risk and subsequent inflammation. We therefore examined associations between individual risk for MDD calculated in early adolescence and levels of inflammation six years later. We use data from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative UK birth cohort of 2,232 children followed to age 18 with 93% retention. Participants' individual risk for developing future MDD was calculated at age 12 using a recently developed prediction model comprising multiple psychosocial factors. Plasma levels of three inflammation biomarkers were measured at age 18: C-reactive protein (CRP), interleukin-6 (IL-6), and a newer biomarker, soluble urokinase plasminogen activator receptor (suPAR), which is thought to reflect the level of systemic chronic inflammation. MDD risk scores calculated at age 12 were positively associated with levels of suPAR (but not CRP or IL-6) at age 18 after adjusting for key covariates (b = 1.70, 95% CI = 0.46 - 2.95, p = 0.007). Adolescents at high risk of MDD (risk scores ≥ 90th centile) had significantly higher mean levels of suPAR six years later than adolescents who had been identified as low risk (risk scores ≤ 10th centile) (b = 0.41, 95% CI = 0.18 - 0.64, p 0.001). Findings support the notion that childhood psychosocial risk for MDD leads to increased levels of low-grade inflammation. If replicated in studies with repeated assessments of inflammation biomarkers throughout childhood and adolescence, these findings would support targeted interventions to reduce inflammation, as measured by suPAR, for adolescents at high risk of MDD to potentially prevent development of depression and physical health problems related to chronic inflammation.

BackgroundNeurodevelopmental disorders (NDs) are associated with experiences of victimization, but mechanisms remain unclear. We explored sex differences and the role of familial factors and externalizing problems in the association between several NDs and violent victimization in adolescence and young adulthood.MethodsIndividuals born in Sweden 1985–1997, residing in Sweden at their 15th birthday, were followed until date of violent victimization causing a hospital visit or death, death due to other causes, emigration, or December 31, 2013, whichever came first. The exposures were diagnoses of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), intellectual disability (ID) and other NDs. We used three different Cox regression models: a crude model, a model adjusted for familial confounding using sibling-comparisons, and a model additionally adjusted for externalizing problems.ResultsAmong 1 344 944 individuals followed, on average, for 5 years, 74 487 were diagnosed with NDs and 37 765 had a hospital visit or died due to violence. ADHD was associated with an increased risk of violent victimization in males [hazard ratio (HR) 2.56; 95% confidence interval (CI) 2.43–2.70) and females (HR 5.39; 95% CI 4.97–5.85). ASD and ID were associated with an increased risk of violent victimization in females only. After adjusting for familial factors and externalizing problems, only ADHD was associated with violent victimization among males (HR 1.27; 95% CI 1.06–1.51) and females (HR 1.69; 95% CI 1.21–2.36).ConclusionsFemales with NDs and males with ADHD are at greater risk of being victim of severe violence during adolescence and young adulthood. Relevant mechanisms include shared familial liability and externalizing problems. ADHD may be independently associated with violent victimization.

Background:Measures to quantify changes in the pace of biological aging in response to intervention are needed to evaluate geroprotective interventions for humans. Previously, we showed that quantification of the pace of biological aging from a DNA-methylation blood test was possible (Belsky et al., 2020). Here, we report a next-generation DNA-methylation biomarker of Pace of Aging, DunedinPACE (for Pace of Aging Calculated from the Epigenome).Methods:We used data from the Dunedin Study 1972–1973 birth cohort tracking within-individual decline in 19 indicators of organ-system integrity across four time points spanning two decades to model Pace of Aging. We distilled this two-decade Pace of Aging into a single-time-point DNA-methylation blood-test using elastic-net regression and a DNA-methylation dataset restricted to exclude probes with low test-retest reliability. We evaluated the resulting measure, named DunedinPACE, in five additional datasets.Results:DunedinPACE showed high test-retest reliability, was associated with morbidity, disability, and mortality, and indicated faster aging in young adults with childhood adversity. DunedinPACE effect-sizes were similar to GrimAge Clock effect-sizes. In analysis of incident morbidity, disability, and mortality, DunedinPACE and added incremental prediction beyond GrimAge.Conclusions:DunedinPACE is a novel blood biomarker of the pace of aging for gerontology and geroscience.Funding:This research was supported by US-National Institute on Aging grants AG032282, AG061378, AG066887, and UK Medical Research Council grant MR/P005918/1.

BACKGROUND AND AIM: Air pollution exposure has been shown to damage the brain but its associations with the development of psychopathology are not fully characterized. This study tested whether ear...

Soluble urokinase-type plasminogen activator receptor (suPAR) is a chronic inflammation marker associated with the development of a range of diseases, including cancer and cardiovascular disease. The genetics of suPAR remain unexplored but may shed light on the biology of the marker and its connection to outcomes. We report a heritability estimate of 60% for the variation in suPAR and performed a genome-wide association meta-analysis on suPAR levels measured in Iceland (N = 35,559) and in Denmark (N = 12,177). We identified 13 independently genome-wide significant sequence variants associated with suPAR across 11 distinct loci. Associated variants were found in and around genes encoding uPAR (PLAUR), its ligand uPA (PLAU), the kidney-disease-associated gene PLA2R1 as well as genes with relations to glycosylation, glycoprotein biosynthesis, and the immune response. These findings provide new insight into the causes of variation in suPAR plasma levels, which may clarify suPAR’s potential role in associated diseases, as well as the underlying mechanisms that give suPAR its prognostic value as a unique marker of chronic inflammation., Dowsett and colleagues used a genome-wide association approach to investigate the genetic influence on soluble urokinase-type plasminogen activator receptor presence in the plasma of humans. Their findings indicate a 60% heritability factor in British twins, and using a wide sample of Northern European genome samples they identify eleven genetic loci associated with an increase or decrease of this chronic inflammation marker.

This study tested implications of new genetic discoveries for understanding the association between parental investment and children's educational attainment. A novel design matched genetic data from 860 British mothers and their children with home-visit measures of parenting: the E-Risk Study. Three findings emerged. First, both mothers' and children's education-associated genetics, summarized in a genome-wide polygenic score, predicted parenting -- a gene-environment correlation. Second, accounting for genetic influences slightly reduced associations between parenting and children's attainment -- indicating some genetic confounding. Third, mothers' genetics influenced children's attainment over and above genetic mother-to-child transmission, via cognitively-stimulating parenting -- an environmentally-mediated effect. Findings imply that, when interpreting parents' effects on children, environmentalists must consider genetic transmission, but geneticists must also consider environmental transmission.

Background Childhood psychotic symptoms have been associated with various psychiatric disorders in adulthood but their role as early markers of poor outcomes during the crucial transition to adulthood is largely unknown. Therefore, we investigated associations between age-12 psychotic symptoms and a range of mental health problems and functional outcomes at age 18. Methods Data were used from the Environmental Risk Longitudinal Twin Study, a nationally representative birth cohort of 2232 twins born in 1994–1995 in England and Wales, followed to age 18 with 93% retention. Childhood psychotic symptoms were assessed in structured interviews at age 12. At age 18, study members’ mental health problems, functional outcomes, risky behaviors, and offending were measured using self-reports and official records. Results Children with psychotic symptoms (N = 125, 5.9%) were more likely to experience a range of mental health problems in young adulthood than children without such symptoms. They were also more likely to be obese, smoke cigarettes, be lonely, be parents, and report a lower quality of life, but not more likely to commit crimes. Childhood psychotic symptoms predicted these poor outcomes over and above other emotional and behavioral problems during childhood. Nevertheless, twin analyses indicated that these associations were largely accounted for by shared family factors. Conclusions Psychotic symptoms in childhood signal risk for pervasive mental health and functional difficulties in young adulthood and thus may provide a useful screen for an array of later problems. However, early psychotic symptoms and poor outcomes may be manifestations of shared environmental and genetic risks.

Young people's life chances can be predicted by characteristics of their neighbourhood1. Children growing up in disadvantaged neighbourhoods exhibit worse physical and mental health and suffer poorer educational and economic outcomes than children growing up in advantaged neighbourhoods. Increasing recognition that aspects of social inequalities tend, in fact, to be geographical inequalities2-5 is stimulating research and focusing policy interest on the role of place in shaping health, behaviour and social outcomes. Where neighbourhood effects are causal, neighbourhood-level interventions can be effective. Where neighbourhood effects reflect selection of families with different characteristics into different neighbourhoods, interventions should instead target families or individuals directly. To test how selection may affect different neighbourhood-linked problems, we linked neighbourhood data with genetic, health and social outcome data for >7,000 European-descent UK and US young people in the E-Risk and Add Health studies. We tested selection/concentration of genetic risks for obesity, schizophrenia, teen pregnancy and poor educational outcomes in high-risk neighbourhoods, including genetic analysis of neighbourhood mobility. Findings argue against genetic selection/concentration as an explanation for neighbourhood gradients in obesity and mental health problems. By contrast, modest genetic selection/concentration was evident for teen pregnancy and poor educational outcomes, suggesting that neighbourhood effects for these outcomes should be interpreted with care.

BackgroundPositive social relationships are known to mitigate the negative effects of stress on mental health. However, the direction of association between social resources and mental health remains unclear, and it is not known whether higher than average levels of social resources confer additional benefits, in the short and longer term.AimsTo investigate the concurrent and longitudinal contribution of higher levels of social resources in reducing the risk of mental health symptoms after exposure to stress at age 45, and to identify life-course precursors of mid-life social resources.MethodThe National Child Development Study (NCDS) is a prospective birth cohort of over 17 000 births in 1958. We tested concurrent and longitudinal associations between different levels of social resources at age 45 and mental health symptoms among individuals exposed to stress and verified whether prior mental health symptoms (age 42) explained these associations. We also tested a range of child, family and adult precursors of mid-life social resources.ResultsHigher than average levels of social resources were required to confer benefits to mental health among individuals exposed to high stress levels, both concurrently at age 45 and in the longer term at age 50. In general, these associations were not attributable to prior mental health symptoms. Key predictors of mid-life social resources included evidence of early sociability.ConclusionsHaving a broad network of social ties and better personal support helps individuals withstand exposure to higher levels of stress. Given that sociable children had better mid-life social resources, early intervention may benefit individuals' social resources later in life.

Children who grow up in neighborhoods with more green vegetation show enhanced cognitive development in specific domains over short timespans. However, it is unknown if neighborhood greenery per se is uniquely predictive of children's overall cognitive development measured across many years. The E-Risk Longitudinal Study, a nationally representative 1994-5 birth-cohort of children in Britain (n = 1658 urban and suburban-dwelling participants), was used to test whether residential neighborhood greenery uniquely predicts children's cognitive development across childhood and adolescence. Greenery exposure was assessed from ages 5 to 18 using the satellite imagery-based normalized difference vegetation index (NDVI) in 1-mile buffers around the home. Fluid and crystalized intellectual performance was assessed in the home at ages 5, 12, and 18 using the Wechsler Intelligence Scale, and executive function, working memory, and attention ability were assessed in the home at age 18 using the Cambridge Neuropsychological Test Automated Battery. Children living in residences surrounded by more neighborhood greenery scored significantly higher, on average, on IQ measures at all ages. However, the association between greenery and cognitive measures did not hold after accounting for family or neighborhood socioeconomic status. After adjustment for study covariates, child greenery exposure was not a significant predictor of longitudinal increases in IQ across childhood and adolescence or of executive function, working memory, or attention ability at age 18. Children raised in greener neighborhoods exhibit better overall cognitive ability, but the association is likely accounted for by family and neighborhood socioeconomic factors., Highlights • We tested whether neighborhood greenery predicts child cognitive development. • Satellite-imagery measures of greenery were related to cognitive ability assessed at ages 5, 12, and 18. • Children raised in greener neighborhoods showed greater ability at all ages. • Children raised in greener neighborhoods also showed greater growth in crystalized cognitive ability from age 5 to 12. • However, the positive associations were best accounted for by family/neighborhood socioeconomic factors.

BackgroundComplex traumas are traumatic experiences that involve multiple interpersonal threats during childhood or adolescence, such as repeated abuse. These traumas are hypothesised to cause more severe psychopathology and poorer cognitive function than other non-complex traumas. However, empirical testing has been limited to clinical/convenience samples and cross-sectional designs.AimsTo investigate psychopathology and cognitive function in young people exposed to complex, non-complex or no trauma, from a population-representative longitudinal cohort, and to consider the role of pre-existing vulnerabilities.MethodParticipants were from the Environmental Risk Longitudinal Twin Study, a population-representative birth cohort of 2232 British children. At age 18 years (93% participation), we assessed lifetime exposure to complex and non-complex trauma, past-year psychopathology and current cognitive function. We also prospectively assessed early childhood vulnerabilities: internalising and externalising symptoms at 5 years of age, IQ at 5 years of age, family history of mental illness, family socioeconomic status and sex.ResultsParticipants exposed to complex trauma had more severe psychopathology and poorer cognitive function at 18 years of age, compared with both trauma-unexposed participants and those exposed to non-complex trauma. Early childhood vulnerabilities predicted risk of later complex trauma exposure, and largely explained associations of complex trauma with cognitive deficits, but not with psychopathology.ConclusionsBy conflating complex and non-complex traumas, current research and clinical practice underestimate the severity of psychopathology, cognitive deficits and pre-existing vulnerabilities linked with complex trauma. A better understanding of the mental health needs of people exposed to complex trauma could inform the development of new, more effective interventions.

Key Points Question Is exposure to outdoor air pollution in childhood and adolescence associated with the development of psychopathology at the transition to adulthood? Findings In this cohort study of 2039 UK-born children followed up for 2 decades, early-life exposure to nitrogen oxides was significantly associated with general psychopathology at 18 years of age, representing greater internalizing, externalizing, and thought disorder symptoms. The associations were not attributable to individual or family-level factors or to disadvantageous neighborhood characteristics. Meaning These findings suggest that exposure to nitrogen oxides in early life may be a nonspecific risk factor for the development of psychopathology as young people begin the transition to adulthood., Importance Air pollution exposure damages the brain, but its associations with the development of psychopathology are not fully characterized. Objective To assess whether air pollution exposure in childhood and adolescence is associated with greater psychopathology at 18 years of age. Design, Setting, and Participants The Environmental-Risk Longitudinal Twin Study is a population-based cohort study of 2232 children born from January 1, 1994, to December 4, 1995, across England and Wales and followed up to 18 years of age. Pollution data generation was completed on April 22, 2020; data were analyzed from April 27 to July 31, 2020. Exposures High-resolution annualized estimates of outdoor nitrogen oxides (NOx) and particulate matter with aerodynamic diameter less than 2.5 μm (PM2.5) linked to home addresses at the ages of 10 and 18 years and then averaged. Main Outcomes and Measures Mental health disorder symptoms assessed through structured interview at 18 years of age and transformed through confirmatory factor analysis into continuous measures of general psychopathology (primary outcome) and internalizing, externalizing, and thought disorder symptoms (secondary outcomes) standardized to a mean (SD) of 100 (15). Hypotheses were formulated after data collection, and analyses were preregistered. Results A total of 2039 participants (1070 [52.5%] female) had full data available. After adjustment for family and individual factors, each interquartile range increment increase in NOx exposure was associated with a 1.40-point increase (95% CI, 0.41-2.38; P = .005) in general psychopathology. There was no association between continuously measured PM2.5 and general psychopathology (b = 0.45; 95% CI, −0.26 to 1.11; P = .22); however, those in the highest quartile of PM2.5 exposure scored 2.04 points higher (95% CI, 0.36-3.72; P = .02) than those in the bottom 3 quartiles. Copollutant models, including both NOx and PM2.5, implicated NOx alone in these significant findings. NOx exposure was associated with all secondary outcomes, although associations were weakest for internalizing (adjusted b = 1.07; 95% CI, 0.10-2.04; P = .03), medium for externalizing (adjusted b = 1.42; 95% CI, 0.53-2.31; P = .002), and strongest for thought disorder symptoms (adjusted b = 1.54; 95% CI, 0.50-2.57; P = .004). Despite NOx concentrations being highest in neighborhoods with worse physical, social, and economic conditions, adjusting estimates for neighborhood characteristics did not change the results. Conclusions and Relevance Youths exposed to higher levels of outdoor NOx experienced greater psychopathology at the transition to adulthood. Air pollution may be a nonspecific risk factor for the development of psychopathology., This cohort study examines the association between exposure to outdoor air pollution in childhood and adolescence with the development of psychopathology at the transition to adulthood.

Exposure to victimization in childhood has been linked to the development of psychosis. However, little is known about how childhood victimization is translated into biological risk for psychosis. One possibility is via increased inflammation. This study aimed to investigate the association between childhood victimization, psychotic experiences (PEs) in adolescence and inflammatory markers using data from a general population cohort. Participants were 1,419 British-born children followed from birth to age 18 years as part of the Environmental Risk Longitudinal Twin Study. Childhood victimization was measured prospectively using multiple sources from birth to age 12 years. PEs were assessed during private interviews with participants at age 18 years for the period since age 12. Plasma C-reactive protein (CRP), interleukin-6 (IL-6), and soluble urokinase plasminogen activator receptor (suPAR) levels were measured from plasma samples collected from participants at 18 years. Young people with both PEs and childhood victimization were more likely to belong to a group with elevated suPAR, CRP and IL-6 levels at 18 years of age (OR = 3.34, 95% CI 1.69–6.59, p = 0.001) than those with no childhood victimization and without PEs. However, this association was attenuated when adjusted for other risk factors for elevated inflammation at age 18 (OR = 1.94, 95% CI 0.94–4.04, p = 0.075). In contrast, presence of PEs without childhood victimization was not significantly associated with age-18 inflammatory markers and neither was childhood victimization without PEs (all p’s greater than 0.05). The current study highlights that inflammatory dysregulation is mostly present in adolescents reporting PEs who also experienced childhood victimization, though this seemed to be largely due to concurrent inflammation-related risk factors.