Environmental Risk Longitudinal Twin Study Research Articles

Adolescent Victimization and Early-Adult Psychopathology: Approaching Causal Inference Using a Longitudinal Twin Study to Rule Out Noncausal Explanations.

Adolescence is the peak age for both victimization and mental disorder onset. Previous research has reported associations between victimization exposure and many psychiatric conditions. However, causality remains controversial. Within the Environmental Risk Longitudinal Twin Study, we tested whether seven types of adolescent victimization increased risk of multiple psychiatric conditions and approached causal inference by systematically ruling out noncausal explanations. Longitudinal within-individual analyses showed that victimization was followed by increased mental health problems over a childhood baseline of emotional/behavioral problems. Discordant-twin analyses showed that victimization increased risk of mental health problems independent of family background and genetic risk. Both childhood and adolescent victimization made unique contributions to risk. Victimization predicted heightened generalized liability (the “p factor”) to multiple psychiatric spectra, including internalizing, externalizing, and thought disorders. Results recommend violence reduction and identification and treatment of adolescent victims to reduce psychiatric burden.

In the eye of the beholder: Perceptions of neighborhood adversity and psychotic experiences in adolescence.

Adolescent psychotic experiences increase risk for schizophrenia and other severe psychopathology in adulthood. Converging evidence implicates urban and adverse neighborhood conditions in the etiology of adolescent psychotic experiences, but the role of young people's personal perceptions of disorder (i.e., physical and social signs of threat) in their neighborhood is unknown. This was examined using data from the Environmental Risk Longitudinal Twin Study, a nationally representative birth cohort of 2,232 British twins. Participants were interviewed at age 18 about psychotic phenomena and perceptions of disorder in the neighborhood. Multilevel, longitudinal, and genetically sensitive analyses investigated the association between perceptions of neighborhood disorder and adolescent psychotic experiences. Adolescents who perceived higher levels of neighborhood disorder were significantly more likely to have psychotic experiences, even after accounting for objectively/independently measured levels of crime and disorder, neighborhood- and family-level socioeconomic status, family psychiatric history, adolescent substance and mood problems, and childhood psychotic symptoms: odds ratio = 1.62, 95% confidence interval [1.27, 2.05], p < .001. The phenotypic overlap between adolescent psychotic experiences and perceptions of neighborhood disorder was explained by overlapping common environmental influences, rC = .88, 95% confidence interval [0.26, 1.00]. Findings suggest that early psychological interventions to prevent adolescent psychotic experiences should explore the role of young people's (potentially modifiable) perceptions of threatening neighborhood conditions.

Is low cognitive functioning a predictor or consequence of major depressive disorder? A test in two longitudinal birth cohorts.

Cognitive impairment has been identified as an important aspect of major depressive disorder (MDD). We tested two theories regarding the association between MDD and cognitive functioning using data from longitudinal cohort studies. One theory, the cognitive reserve hypothesis, suggests that higher cognitive ability in childhood decreases risk of later MDD. The second, the scarring hypothesis, instead suggests that MDD leads to persistent cognitive deficits following disorder onset. We tested both theories in the Dunedin Study, a population-representative cohort followed from birth to midlife and assessed repeatedly for both cognitive functioning and psychopathology. We also used data from the Environmental Risk Longitudinal Twin Study to test whether childhood cognitive functioning predicts future MDD risk independent of family-wide and genetic risk using a discordant twin design. Contrary to both hypotheses, we found that childhood cognitive functioning did not predict future risk of MDD, nor did study members with a past history of MDD show evidence of greater cognitive decline unless MDD was accompanied by other comorbid psychiatric conditions. Our results thus suggest that low cognitive functioning is related to comorbidity, but is neither an antecedent nor an enduring consequence of MDD. Future research may benefit from considering cognitive deficits that occur during depressive episodes from a transdiagnostic perspective.

From Childhood Conduct Problems to Poor Functioning at Age 18 Years: Examining Explanations in a Longitudinal Cohort Study

ObjectiveChildhood conduct problems are associated with poor functioning in early adulthood. We tested a series of hypotheses to understand the mechanisms underlying this association.MethodWe used data from the Environmental Risk (E-Risk) Longitudinal Twin Study, a birth cohort of 2,232 twins born in England and Wales in 1994 and 1995, followed up to age 18 years with 93% retention. Severe conduct problems in childhood were assessed at ages 5, 7, and 10 years using parent and teacher reports. Poor functioning at age 18 years, including cautions and convictions, daily cigarette smoking, heavy drinking, and psychosocial difficulties, was measured through interviews with participants and official crime record searches.ResultsParticipants 18 years old with versus without a childhood history of severe conduct problems had greater rates of each poor functional outcome, and they were more likely to experience multiple poor outcomes. This association was partly accounted for by concurrent psychopathology in early adulthood, as well as by early familial risk factors, both genetic and environmental. Childhood conduct problems, however, continued to predict poor outcomes at age 18 years after accounting for these explanations.ConclusionChildren with severe conduct problems display poor functioning at age 18 years because of concurrent problems in early adulthood and familial risk factors originating in childhood. However, conduct problems also exert a lasting effect on young people’s lives independent of these factors, pointing to early conduct problems as a target for early interventions aimed at preventing poor functional outcomes.

Measuring childhood maltreatment to predict early-adult psychopathology: Comparison of prospective informant-reports and retrospective self-reports

Both prospective informant-reports and retrospective self-reports may be used to measure childhood maltreatment, though both methods entail potential limitations such as underestimation and memory biases. The validity and utility of standard measures of childhood maltreatment requires clarification in order to inform the design of future studies investigating the mental health consequences of maltreatment. The present study assessed agreement between prospective informant-reports and retrospective self-reports of childhood maltreatment, as well as the comparative utility of both reports for predicting a range of psychiatric problems at age 18. Data were obtained from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally-representative birth cohort of 2232 children followed to 18 years of age (with 93% retention). Childhood maltreatment was assessed in two ways: (i) prospective informant-reports from caregivers, researchers, and clinicians when children were aged 5, 7, 10 and 12; and (ii) retrospective self-reports of maltreatment experiences occurring up to age 12, obtained at age 18 using the Childhood Trauma Questionnaire. Participants were privately interviewed at age 18 concerning several psychiatric problems including depression, anxiety, self-injury, alcohol/cannabis dependence, and conduct disorder. There was only slight to fair agreement between prospective and retrospective reports of childhood maltreatment (all Kappa's ≤ 0.31). Both prospective and retrospective reports of maltreatment were associated with age-18 psychiatric problems, though the strongest associations were found when maltreatment was retrospectively self-reported. These findings indicate that prospective and retrospective reports of childhood maltreatment capture largely non-overlapping groups of individuals. Young adults who recall being maltreated have a particularly elevated risk for psychopathology.

Associations between adolescent cannabis use and neuropsychological decline: a longitudinal co-twin control study.

This study tested whether adolescents who used cannabis or met criteria for cannabis dependence showed neuropsychological impairment prior to cannabis initiation and neuropsychological decline from before to after cannabis initiation. A longitudinal co-twin control study. Participants were 1989 twins from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative birth cohort of twins born in England and Wales from 1994 to 1995. Frequency of cannabis use and cannabis dependence were assessed at age 18. Intelligence quotient (IQ) was obtained at ages 5, 12 and 18. Executive functions were assessed at age 18. Compared with adolescents who did not use cannabis, adolescents who used cannabis had lower IQ in childhood prior to cannabis initiation and lower IQ at age 18, but there was little evidence that cannabis use was associated with IQ decline from ages 12-18. For example, adolescents with cannabis dependence had age 12 and age 18 IQ scores that were 5.61 (t=-3.11, P=0.002) and 7.34 IQ points (t=-5.27, P<0.001) lower than adolescents without cannabis dependence, but adolescents with cannabis dependence did not show greater IQ decline from age 12-18 (t=-1.27, P=0.20). Moreover, adolescents who used cannabis had poorer executive functions at age 18 than adolescents who did not use cannabis, but these associations were generally not apparent within twin pairs. For example, twins who used cannabis more frequently than their co-twin performed similarly to their co-twin on five of six executive function tests (Ps>0.10). The one exception was that twins who used cannabis more frequently than their co-twin performed worse on one working memory test (Spatial Span reversed; β=-0.07, P=0.036). Short-term cannabis use in adolescence does not appear to cause IQ decline or impair executive functions, even when cannabis use reaches the level of dependence. Family background factors explain why adolescent cannabis users perform worse on IQ and executive function tests.

Childhood victimization and inflammation in young adulthood: A genetically sensitive cohort study

ObjectiveChildhood victimization is an important risk factor for later immune-related disorders. Previous evidence has demonstrated that childhood victimization is associated with elevated levels of inflammation biomarkers measured decades after exposure. However, it is unclear whether this association is (1) already detectable in young people, (2) different in males and females, and (3) confounded by genetic liability to inflammation. Here we sought to address these questions. MethodParticipants were 2232 children followed from birth to age 18years as part of the Environmental Risk (E-Risk) Longitudinal Twin Study. Childhood victimization was measured prospectively from birth to age 12years. Inflammation was measured through C-reactive protein (CRP) levels in dried blood spots at age 18years. Latent genetic liability for high inflammation levels was assessed through a twin-based method. ResultsGreater exposure to childhood victimization was associated with higher CRP levels at age 18 (serum-equivalent means were 0.65 in non-victimized Study members, 0.74 in those exposed to one victimization type, and 0.81 in those exposed to poly-victimization; p=0.018). However, this association was driven by a significant association in females (serum-equivalent means were 0.75 in non-victimized females, 0.87 in those exposed to one type of victimization, and 1.19 in those exposed to poly-victimization; p=0.010), while no significant association was observed in males (p=0.19). Victimized females showed elevated CRP levels independent of latent genetic influence, as well as childhood socioeconomic status, and waist-hip ratio and body temperature at the time of CRP assessment. ConclusionChildhood victimization is associated with elevated CRP levels in young women, independent of latent genetic influences and other key risk factors. These results strengthen causal inference about the effects of childhood victimization on inflammation levels in females by accounting for potential genetic confounding.

Protective Factors for Psychotic Symptoms Among Poly-victimized Children.

BackgroundExperiencing victimization in early life has been repeatedly shown to be associated with the emergence of psychotic symptoms in childhood. However, most victimized children do not develop psychotic symptoms and why this occurs is not fully understood. This study investigated which individual, family-level, and wider community characteristics were associated with an absence of psychotic symptoms among children at risk for psychosis by virtue of their exposure to multiple victimization experiences (poly-victimization).MethodsParticipants were from the Environmental Risk Longitudinal Twin Study, a nationally representative cohort of 2232 UK-born twins. Exposure to maltreatment, bullying and domestic violence prior to age 12 was determined from interviews with mothers, children, and observations by research workers at ages 5, 7, 10, and 12. Children were interviewed about psychotic symptoms at age 12. Protective factors were measured at ages 5, 7, 10, and 12.ResultsChildhood poly-victimization was associated with age-12 psychotic symptoms (OR = 4.61, 95% CI 2.82–7.52), but the majority of poly-victimized children did not report symptoms (80.7%). Having a relatively high IQ, more positive atmosphere at home, and higher levels of neighborhood social cohesion were found to be protective against childhood psychotic symptoms among poly-victimized children and also in the whole sample. However, “protected” poly-victimized children displayed elevated levels of other mental health problems compared to nonvictimized children.ConclusionsChildren’s characteristics, family context, and the wider community were all found to protect children from developing early psychotic symptoms, even when they were victimized multiple times. These findings indicate targets for multilevel preventive interventions.

Buffering effects of safe, supportive, and nurturing relationships among women with childhood histories of maltreatment.

Adults who were victims of childhood maltreatment tend to have poorer health compared with adults who did not experience abuse. However, many are in good health. We tested whether safe, supportive, and nurturing relationships buffer women with a history of childhood maltreatment from poor health outcomes in later life. Participants included women from the Environmental Risk (E-Risk) Longitudinal Twin Study who were involved in an intimate relationship at some point by the time their twin children were 10 years old. Women were initially interviewed in 1999-2000 (mean age = 33 years) and 2, 5, and 7 years later. They reported on their physical and mental health, and their health-risk behaviours. Compared with women who did not experience abuse in childhood, women with histories of maltreatment were at elevated risk for mental, physical, and health-risk behaviours, including major depressive disorder, sleep, and substance use problems. Cumulatively, safe, supportive, and nurturing relationships characterized by a lack of violence, emotional intimacy, and social support buffered women with a history of maltreatment from poor health outcomes. Our findings emphasize that negative social determinants of health - such as a childhood history of maltreatment - confer risk for psychopathology and other physical health problems. If, however, a woman's current social circumstances are sufficiently positive, they can promote good health, particularly in the face of past adversity.

Cumulative Effects of Neighborhood Social Adversity and Personal Crime Victimization on Adolescent Psychotic Experiences.

Background: Little is known about the impact of urbanicity, adverse neighborhood conditions and violent crime victimization on the emergence of adolescent psychotic experiences. Methods: Participants were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally-representative cohort of 2232 British twins who were interviewed about adolescent psychotic experiences at age 18. Urbanicity, neighborhood characteristics, and personal victimization by violent crime were measured during childhood and adolescence via geocoded census data, surveys of over 5000 immediate neighbors of the E-Risk participants, and interviews with participants themselves. Results: Adolescents raised in urban vs rural neighborhoods were significantly more likely to have psychotic experiences (OR = 1.67, 95% CI = 1.21–2.30, P = .002). This association remained significant after considering potential confounders including family socioeconomic status, family psychiatric history, and adolescent substance problems (OR = 1.43, 95% CI = 1.01–2.03, P = .042), but became nonsignificant after considering adverse social conditions in urban neighborhoods such as low social cohesion and high neighborhood disorder (OR = 1.35, 95% CI = 0.94–1.92, P = .102). The combined association of adverse neighborhood social conditions and personal crime victimization with adolescent psychotic experiences (adjusted OR = 4.86, 95% CI = 3.28–7.20, P < .001) was substantially greater than for either exposure alone, highlighting a potential interaction between neighborhood conditions and crime victimization (interaction contrast ratio = 1.81, 95% CI = −0.03 to 3.65) that was significant at the P = .054 level. Conclusions: Cumulative effects of adverse neighborhood social conditions and personal victimization by violent crime during upbringing partly explain why adolescents in urban settings are more likely to report psychotic experiences. Early intervention efforts for psychosis could be targeted towards victimized youth living in urban and socially adverse neighborhoods.

Sleeping with one eye open: loneliness and sleep quality in young adults.

Feelings of loneliness are common among young adults, and are hypothesized to impair the quality of sleep. In the present study, we tested associations between loneliness and sleep quality in a nationally representative sample of young adults. Further, based on the hypothesis that sleep problems in lonely individuals are driven by increased vigilance for threat, we tested whether past exposure to violence exacerbated this association. Data were drawn from the Environmental Risk (E-Risk) Longitudinal Twin Study, a birth cohort of 2232 twins born in England and Wales in 1994 and 1995. We measured loneliness using items from the UCLA Loneliness Scale, and sleep quality using the Pittsburgh Sleep Quality Index. We controlled for covariates including social isolation, psychopathology, employment status and being a parent of an infant. We examined twin differences to control for unmeasured genetic and family environment factors. Feelings of loneliness were associated with worse overall sleep quality. Loneliness was associated specifically with subjective sleep quality and daytime dysfunction. These associations were robust to controls for covariates. Among monozygotic twins, within-twin pair differences in loneliness were significantly associated with within-pair differences in sleep quality, indicating an association independent of unmeasured familial influences. The association between loneliness and sleep quality was exacerbated among individuals exposed to violence victimization in adolescence or maltreatment in childhood. Loneliness is robustly associated with poorer sleep quality in young people, underscoring the importance of early interventions to mitigate the long-term outcomes of loneliness. Special care should be directed towards individuals who have experienced victimization.

Childhood Bullying Victimization and Overweight in Young Adulthood: A Cohort Study.

To test whether bullied children have an elevated risk of being overweight in young adulthood and whether this association is: (1) consistent with a dose-response relationship, namely, its strength increases with the chronicity of victimization; (2) consistent across different measures of overweight; (3) specific to bullying and not explained by co-occurring maltreatment; (4) independent of key potential confounders; and (5) consistent with the temporal sequence of bullying preceding overweight. A representative birth cohort of 2,232 children was followed to age 18 years as part of the Environmental Risk Longitudinal Twin Study. Childhood bullying victimization was reported by mothers and children during primary school and early secondary school. At the age-18 follow-up, we assessed a categorical measure of overweight, body mass index, and waist-hip ratio. Indicators of overweight were also collected at ages 10 and 12. Co-twin body mass and birth weight were used to index genetic and fetal liability to overweight, respectively. Bullied children were more likely to be overweight than non-bullied children at age 18, and this association was (1) strongest in chronically bullied children (odds ratio = 1.69; 95% confidence interval [CI] = 1.21-2.35); (2) consistent across measures of overweight (body mass index: b = 1.12; 95% CI = 0.37-1.87; waist-hip ratio: b = 1.76; 95% CI = 0.84-2.69); (3) specific to bullying and not explained by co-occurring maltreatment; (4) independent of child socioeconomic status, food insecurity, mental health, and cognition, and pubertal development; and (5) not present at the time of bullying victimization, and independent of childhood weight and genetic and fetal liability. Childhood bullying victimization predicts overweight in young adulthood.

ADHD and Sleep Quality: Longitudinal Analyses From Childhood to Early Adulthood in a Twin Cohort

Attention-deficit/hyperactivity disorder (ADHD) is associated with poor sleep quality, but there is more to learn about the longitudinal association and aetiology of this association. We investigated the following: (a) Is there an association between childhood ADHD and poor sleep quality in young adulthood? (b) Is this driven by the long-term effects of childhood ADHD or concurrent associations with ADHD in young adulthood? (c) To what extent do genetic and environmental influences explain the overlap between symptoms of ADHD and poor sleep quality? Participants were from the Environmental Risk Longitudinal Twin Study of 2,232 twin children born in the United Kingdom in 1994–1995. We ascertained ADHD diagnoses at ages 5, 7, 10, 12, and 18. We assessed sleep quality using the Pittsburgh Sleep Quality Index at age 18. We used regression models to examine longitudinal associations and bivariate twin modelling to test genetic and environmental influences. Children with ADHD had poorer sleep quality in young adulthood, but only if their ADHD persisted. Adults with ADHD had more sleep problems than those without ADHD, over and above psychiatric comorbidity and maternal insomnia. ADHD and sleep problems in young adulthood were associated because of genetic (55%) and nonshared environmental influences (45%). Should ADHD remit, children with ADHD do not appear to have an increased risk of later sleep problems. Good quality sleep is important for multiple areas of functioning, and a better understanding of why adults with ADHD have poorer sleep quality will further the goal of improving treatments.

Parental monitoring and knowledge: Testing bidirectional associations with youths' antisocial behavior.

In the present study, we used separate measures of parental monitoring and parental knowledge and compared their associations with youths' antisocial behavior during preadolescence, between the ages of 10 and 12. Parental monitoring and knowledge were reported by mothers, fathers, and youths taking part in the Environmental Risk (E-Risk) Longitudinal Twin Study that follows 1,116 families with twins. Information on youths' antisocial behavior was obtained from mothers as well as teachers. We report two main findings. First, longitudinal cross-lagged models revealed that greater parental monitoring did not predict less antisocial behavior later, once family characteristics were taken into account. Second, greater youth antisocial behavior predicted less parental knowledge later. This effect of youths' behavior on parents' knowledge was consistent across mothers', fathers', youths', and teachers' reports, and robust to controls for family confounders. The association was partially genetically mediated according to a Cholesky decomposition twin model; youths' genetically influenced antisocial behavior led to a decrease in parents' knowledge of youths' activities. These two findings question the assumption that greater parental monitoring can reduce preadolescents' antisocial behavior. They also indicate that parents' knowledge of their children's activities is influenced by youths' behavior.

Evaluation of the Persistence, Remission, and Emergence of Attention-Deficit/Hyperactivity Disorder in Young Adulthood.

Attention-deficit/hyperactivity disorder (ADHD) is now recognized to occur in adulthood and is associated with a range of negative outcomes. However, less is known about the prospective course of ADHD into adulthood, the risk factors for its persistence, and the possibility of its emergence in young adulthood in nonclinical populations. To investigate childhood risk factors and young adult functioning of individuals with persistent, remitted, and late-onset young adult ADHD. The study sample was the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative birth cohort of 2232 twins born in England and Wales from January 1, 1994, to December 4, 1995. Evaluation of childhood ADHD (ages 5, 7, 10, and 12 years) included prenatal and perinatal factors, clinical characteristics, and aspects of the family environment. Among participants aged 18 years, ADHD symptoms and associated impairment, overall functioning, and other mental health disorders were examined. Data analysis was conducted from February 19 to September 10, 2015. Attention-deficit/hyperactivity disorder according to DSM-IV diagnostic criteria in childhood and DSM-5 diagnostic criteria in young adulthood. Of 2232 participants in the E-Risk Study, 2040 were included in the present analysis. In total, 247 individuals met diagnostic criteria for childhood ADHD; of these, 54 (21.9%) also met diagnostic criteria for the disorder at age 18 years. Persistence was associated with more symptoms (odds ratio [OR], 1.11 [95% CI, 1.04-1.19]) and lower IQ (OR, 0.98 [95% CI, 0.95-1.00]). At age 18 years, individuals with persistent ADHD had more functional impairment (school/work: OR, 3.30 [95% CI, 2.18-5.00], home/with friends: OR, 6.26 [95% CI, 3.07-12.76]), generalized anxiety disorder (OR, 5.19 [95% CI, 2.01-13.38]), conduct disorder (OR, 2.03 [95% CI, 1.03-3.99]), and marijuana dependence (OR, 2.88 [95% CI, 1.07-7.71]) compared with those whose ADHD remitted. Among 166 individuals with adult ADHD, 112 (67.5%) did not meet criteria for ADHD at any assessment in childhood. Results from logistic regressions indicated that individuals with late-onset ADHD showed fewer externalizing problems (OR, 0.93 [95% CI, 0.91-0.96]) and higher IQ (OR, 1.04 [95% CI, 1.02-1.07]) in childhood compared with the persistent group. However, at age 18 years, those with late-onset ADHD demonstrated comparable ADHD symptoms and impairment as well as similarly elevated rates of mental health disorders. We identified heterogeneity in the DSM-5 young adult ADHD population such that this group consisted of a large, late-onset ADHD group with no childhood diagnosis, and a smaller group with persistent ADHD. The extent to which childhood-onset and late-onset adult ADHD may reflect different causes has implications for genetic studies and treatment of ADHD.

Why Are Children in Urban Neighborhoods at Increased Risk for Psychotic Symptoms? Findings From a UK Longitudinal Cohort Study

Background:Urban upbringing is associated with a 2-fold adulthood psychosis risk, and this association replicates for childhood psychotic symptoms. No study has investigated whether specific features of urban neighborhoods increase children’s risk for psychotic symptoms, despite these early psychotic phenomena elevating risk for schizophrenia and other psychiatric disorders in adulthood.Methods:Analyses were conducted on over 2000 children from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally-representative cohort of UK-born twins. Neighborhood-level characteristics were assessed for each family via: a geodemographic discriminator indexing neighborhood-level deprivation, postal surveys of over 5000 residents living alongside the children, and in-home interviews with the children’s mothers. Children were interviewed about psychotic symptoms at age 12. Analyses were adjusted for important family-level confounders including socioeconomic status (SES), psychiatric history, and maternal psychosis.Results:Urban residency at age-5 (OR = 1.80, 95% CI = 1.16–2.77) and age-12 (OR = 1.76, 95% CI = 1.15–2.69) were both significantly associated with childhood psychotic symptoms, but not with age-12 anxiety, depression, or antisocial behavior. The association was not attributable to family SES, family psychiatric history, or maternal psychosis, each implicated in childhood mental health. Low social cohesion, together with crime victimization in the neighborhood explained nearly a quarter of the association between urbanicity and childhood psychotic symptoms after considering family-level confounders.Conclusions:Low social cohesion and crime victimization in the neighborhood partly explain why children in cities have an elevated risk of developing psychotic symptoms. Greater understanding of the mechanisms leading from neighborhood-level exposures to psychotic symptoms could help target interventions for emerging childhood psychotic symptoms.

Methylomic markers of persistent childhood asthma: a longitudinal study of asthma-discordant monozygotic twins.

BackgroundAsthma is the most common chronic inflammatory disorder in children. The aetiology of asthma pathology is complex and highly heterogeneous, involving the interplay between genetic and environmental risk factors that is hypothesized to involve epigenetic processes. Our aim was to explore whether methylomic variation in early childhood is associated with discordance for asthma symptoms within monozygotic (MZ) twin pairs recruited from the Environmental Risk (E-Risk) longitudinal twin study. We also aimed to identify differences in DNA methylation that are associated with asthma that develops in childhood and persists into early adulthood as these may represent useful prognostic biomarkers.ResultsWe examined genome-wide patterns of DNA methylation in buccal cell samples collected from 37 MZ twin pairs discordant for asthma at age 10. DNA methylation at individual CpG sites demonstrated significant variability within discordant MZ twin pairs with the top-ranked nominally significant differentially methylated position (DMP) located in the HGSNAT gene. We stratified our analysis by assessing DNA methylation differences in a sub-group of MZ twin pairs who remained persistently discordant for asthma at age 18. The top-ranked nominally significant DMP associated with persisting asthma is located in the vicinity of the HLX gene, which has been previously implicated in childhood asthma.ConclusionsWe identified DNA methylation differences associated with childhood asthma in peripheral DNA samples from discordant MZ twin pairs. Our data suggest that differences in DNA methylation associated with childhood asthma which persists into early adulthood are distinct from those associated with asthma which remits.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-015-0163-4) contains supplementary material, which is available to authorized users.

Etiology of Pervasive Versus Situational Antisocial Behaviors: A Multi-Informant Longitudinal Cohort Study.

The aim of this study was to disentangle pervasive from situational antisocial behaviors using multiple informants, and to investigate their genetic and environmental etiologies in preadolescence and across time. Antisocial behaviors were assessed in 2,232 twins from the Environmental Risk (E‐Risk) Longitudinal Twin Study at ages 5 and 12. Pervasive antisocial behaviors were defined as behaviors that mothers, teachers, interviewers, and twins themselves agreed on. Results from a psychometric model indicated that the variation in children's pervasive antisocial behaviors was mostly accounted for by familial influences that originated in childhood, whereas situational behaviors were explained by newly emerging nonshared environmental and genetic influences. This study shows that children's pervasive and situational antisocial behaviors have distinct etiologies that could guide research and treatment.

Measuring adolescents' exposure to victimization: The Environmental Risk (E-Risk) Longitudinal Twin Study.

This paper presents multilevel findings on adolescents' victimization exposure from a large longitudinal cohort of twins. Data were obtained from the Environmental Risk (E-Risk) Longitudinal Twin Study, an epidemiological study of 2,232 children (1,116 twin pairs) followed to 18 years of age (with 93% retention). To assess adolescent victimization, we combined best practices in survey research on victimization with optimal approaches to measuring life stress and traumatic experiences, and introduce a reliable system for coding severity of victimization. One in three children experienced at least one type of severe victimization during adolescence (crime victimization, peer/sibling victimization, Internet/mobile phone victimization, sexual victimization, family violence, maltreatment, or neglect), and most types of victimization were more prevalent among children from low socioeconomic backgrounds. Exposure to multiple victimization types was common, as was revictimization; over half of those physically maltreated in childhood were also exposed to severe physical violence in adolescence. Biometric twin analyses revealed that environmental factors had the greatest influence on most types of victimization, while severe physical maltreatment from caregivers during adolescence was predominantly influenced by heritable factors. The findings from this study showcase how distinct levels of victimization measurement can be harmonized in large-scale studies of health and development.

Methylomic analysis of monozygotic twins discordant for childhood psychotic symptoms

Childhood psychotic symptoms are associated with increased rates of schizophrenia, other psychiatric disorders, and suicide attempts in adulthood; thus, elucidating early risk indicators is crucial to target prevention efforts. There is considerable discordance for psychotic symptoms between monozygotic twins, indicating that child-specific non-genetic factors must be involved. Epigenetic processes may constitute one of these factors and have not yet been investigated in relation to childhood psychotic symptoms. Therefore, this study explored whether differences in DNA methylation at age 10 were associated with monozygotic twin discordance for psychotic symptoms at age 12. The Environmental Risk (E-Risk) Longitudinal Twin Study cohort of 2,232 children (1,116 twin pairs) was assessed for age-12 psychotic symptoms and 24 monozygotic twin pairs discordant for symptoms were identified for methylomic comparison. Children provided buccal samples at ages 5 and 10. DNA was bisulfite modified and DNA methylation was quantified using the Infinium HumanMethylation450 array. Differentially methylated positions (DMPs) associated with psychotic symptoms were subsequently tested in post-mortem prefrontal cortex tissue from adult schizophrenia patients and age-matched controls. Site-specific DNA methylation differences were observed at age 10 between monozygotic twins discordant for age-12 psychotic symptoms. Similar DMPs were not found at age 5. The top-ranked psychosis-associated DMP (cg23933044), located in the promoter of the C5ORF42 gene, was also hypomethylated in post-mortem prefrontal cortex brain tissue from schizophrenia patients compared to unaffected controls. These data tentatively suggest that epigenetic variation in peripheral tissue is associated with childhood psychotic symptoms and may indicate susceptibility to schizophrenia and other mental health problems.