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Developmental or fetal programming has emerged as a major model for understanding the early and persisting effects of prenatal exposures on the health and development of the child and adult. We leverage the power of a 14-year prospective study to examine the persisting effects of prenatal anxiety, a key candidate in the developmental programming model, on symptoms of behavioral and emotional problems across five occasions of measurement from age 4 to 13 years. The study is based on the Avon Longitudinal Study of Parents and Children cohort, a prospective, longitudinal study of a large community sample in the west of England (n = 7,944). Potential confounders included psychosocial and obstetric risk, postnatal maternal mood, paternal pre- and postnatal mood, and parenting. Results indicated that maternal prenatal anxiety predicted persistently higher behavioral and emotional symptoms across childhood with no diminishment of effect into adolescence. Elevated prenatal anxiety (top 15%) was associated with a twofold increase in risk of a probable child mental disorder, 12.31% compared with 6.83%, after allowing for confounders. Results were similar with prenatal depression. These analyses provide some of the strongest evidence to date that prenatal maternal mood has a direct and persisting effect on her child's psychiatric symptoms and support an in utero programming hypothesis.

Little is currently known about how maternal depression symptoms and unhealthy nutrition during pregnancy may developmentally interrelate to negatively affect child cognitive function. To test whether prenatal maternal depression symptoms predict poor prenatal nutrition, and whether this in turn prospectively associates with reduced postnatal child cognitive function. In 6979 mother-offspring pairs participating in the Avon Longitudinal Study of Parents and Children (ALSPAC) in the UK, maternal depression symptoms were assessed five times between 18 weeks gestation and 33 months old. Maternal reports of the nutritional environment were assessed at 32 weeks gestation and 47 months old, and child cognitive function was assessed at age 8 years. During gestation, higher depressive symptoms were related to lower levels of healthy nutrition and higher levels of unhealthy nutrition, each of which in turn was prospectively associated with reduced cognitive function. These results were robust to postnatal depression symptoms and nutrition, as well as a range of potential prenatal and postnatal confounds (i.e. poverty, teenage mother, low maternal education, parity, birth complications, substance use, criminal lifestyle, partner cruelty towards mother). Prenatal interventions aimed at the well-being of children of parents with depression should consider targeting the nutritional environment.

This study explored whether early elementary school aged children's externalizing problems impede academic functioning and foster negative social experiences such as peer victimization, thereby making these children vulnerable for developing internalizing problems and possibly increasing their externalizing problems. It also explored whether early internalizing problems contributed to an increase in externalizing problems. The study examined 1,558 Canadian children from ages 6 to 8 years. Externalizing and internalizing problems, peer victimization, and school achievement were assessed annually. Externalizing problems lead to academic underachievement and experiences of peer victimization. Academic underachievement and peer victimization, in turn, predicted increases in internalizing problems and in externalizing problems. These pathways applied equally to boys and girls. No links from internalizing to externalizing problems were found.

There is an extensive body of literature linking ADHD to overweight and obesity. Research indicates that impulsivity features of ADHD account for a degree of this overlap. The neural and polygenic correlates of this association have not been thoroughly examined. In participants of the IMAGEN study, we found that impulsivity symptoms and body mass index (BMI) were associated (r = 0.10, n = 874, p = 0.014 FWE corrected), as were their respective polygenic risk scores (PRS) (r = 0.17, n = 874, p = 6.5 × 10−6 FWE corrected). We then examined whether the phenotypes of impulsivity and BMI, and the PRS scores of ADHD and BMI, shared common associations with whole-brain grey matter and the Monetary Incentive Delay fMRI task, which associates with reward-related impulsivity. A sparse partial least squared analysis (sPLS) revealed a shared neural substrate that associated with both the phenotypes and PRS scores. In a last step, we conducted a bias corrected bootstrapped mediation analysis with the neural substrate score from the sPLS as the mediator. The ADHD PRS associated with impulsivity symptoms (b = 0.006, 90% CIs = 0.001, 0.019) and BMI (b = 0.009, 90% CIs = 0.001, 0.025) via the neuroimaging substrate. The BMI PRS associated with BMI (b = 0.014, 95% CIs = 0.003, 0.033) and impulsivity symptoms (b = 0.009, 90% CIs = 0.001, 0.025) via the neuroimaging substrate. A common neural substrate may (in part) underpin shared genetic liability for ADHD and BMI and the manifestation of their (observable) phenotypic association.

In general, mothers with depression experience more environmental and family risk factors, and lead riskier lifestyles, than mothers who are not depressed. To test whether the exposure of a child to risk factors associated with mental health adds to the prediction of child psychopathology beyond exposure to maternal depression. In 7429 mother-offspring pairs participating in the Avon Longitudinal Study of Parents and Children in the UK, maternal depression was assessed when the children were aged 1.5 years; multiple risk factor exposures were examined between birth and 2 years of age; and DSM-IV-based externalising and internalising diagnoses were evaluated when the children were 7.5 years of age. Children of clinically depressed mothers were exposed to more risk factors associated with maternal mental health. Maternal depression increased diagnoses of externalising and internalising disorders, but a substantial portion of these associations was explained by increased risk factor exposure (41% for externalising and 37% for internalising disorders). At the same time, these risk exposures significantly increased the odds of both externalising and internalising diagnoses, over and above the influence of maternal depression. Children of clinically depressed mothers are exposed to both maternal psychopathology and risks that are associated with maternal mental health. These results may explain why treating mothers with depression shows beneficial effects for children, but does not completely neutralise the increased risk of psychopathology and impairment.

Attention-deficit and hyperactivity disorder (ADHD) is a common childhood disorder with a substantial genetic component. However, the extent to which epigenetic mechanisms play a role in the etiology of the disorder is unknown. We performed epigenome-wide association studies (EWAS) within the Pregnancy And Childhood Epigenetics (PACE) Consortium to identify DNA methylation sites associated with ADHD symptoms at two methylation assessment periods: birth and school age. We examined associations of both DNA methylation in cord blood with repeatedly assessed ADHD symptoms (age 4–15 years) in 2477 children from 5 cohorts and of DNA methylation at school age with concurrent ADHD symptoms (age 7–11 years) in 2374 children from 9 cohorts, with 3 cohorts participating at both timepoints. CpGs identified with nominal significance ( p  < 0.05) in either of the EWAS were correlated between timepoints ( ρ  = 0.30), suggesting overlap in associations; however, top signals were very different. At birth, we identified nine CpGs that predicted later ADHD symptoms ( p  < 1 × 10 –7 ), including ERC2 and CREB5 . Peripheral blood DNA methylation at one of these CpGs (cg01271805 in the promoter region of ERC2 , which regulates neurotransmitter release) was previously associated with brain methylation. Another (cg25520701) lies within the gene body of CREB5 , which previously was associated with neurite outgrowth and an ADHD diagnosis. In contrast, at school age, no CpGs were associated with ADHD with p  < 1 × 10 −7 . In conclusion, we found evidence in this study that DNA methylation at birth is associated with ADHD. Future studies are needed to confirm the utility of methylation variation as biomarker and its involvement in causal pathways.

This study used a sample of 551 children surveyed yearly from ages 6 to 13 to examine the longitudinal associations among early behavior, middle-childhood peer rejection and friendedness, and early-adolescent depressive symptoms, loneliness, and delinquency. The study tested a sequential mediation hypothesis in which (a) behavior problems in the early school years are associated with middle-childhood peer rejection and (b) rejection, in turn, leads to lower friendedness and subsequently higher adolescent internalizing-but not externalizing-problems. Results supported this sequential mediation model for internalizing outcomes and revealed an additional path from early disruptiveness to loneliness via peer rejection alone. No evidence of sequential mediation was observed for delinquency.

There is increasing evidence that youth who follow the early onset persistent (EOP), adolescent-onset (AO) and childhood-limited (CL) trajectories of conduct problems show varying patterns of health, mental health, educational, and social outcomes in adulthood. However, there has been no systematic review and meta-analysis on outcomes associated with different conduct problems trajectories. We systematically reviewed the literature of longitudinal studies considering outcomes of three conduct problems trajectories: EOP, AO, and CL compared with individuals with low levels of conduct problems (low). We performed a series of meta-analyses comparing each trajectory to the low group for eight different outcomes in early adulthood or later. Thirteen studies met our inclusion criteria. Outcomes were mental health (depression), cannabis use, alcohol use, self-reported aggression, official records of antisocial behaviour, poor general health, poor education, and poor employment. Overall, EOP individuals showed significant higher risk of poor outcome followed by AO individuals, CL individuals, and finally participants in the low group. All conduct problems trajectories showed higher risk of poor psychosocial outcomes compared to the low group, but the magnitude of risk differed across trajectories, with a general trend for the EOP to perform significantly worse, followed by the AO and CL. Early intervention is recommended across domains to maximise likelihood of desistance from antisocial behaviour and improvement on several psychosocial outcomes.

Depression and psychosis are often comorbid; they also have overlapping genetic and environmental risk factors, including trauma and area-level exposures. The present study aimed to advance understanding of this comorbidity via a network approach, by (1) identifying bridge nodes that connect clusters of lifetime depression and psychosis symptoms and (2) evaluating the influence of polygenic and environmental risk factors in these symptoms. This study included data from European ancestry participants in UK Biobank, a large population-based sample ( N  = 77,650). In Step 1, a network model identified bridge nodes between lifetime symptoms of depression and psychosis and functional impairment. In Step 2, genetic and environmental risk factors were incorporated to examine the degree to which symptoms associated with polygenic risk scores for depression and schizophrenia, lifetime exposure to trauma and area-level factors (including deprivation, air pollution and greenspace). Feelings of worthlessness, beliefs in unreal conspiracy against oneself, depression impairment and psychosis impairment emerged as bridges between depression and psychosis symptoms. Polygenic risk scores for depression and schizophrenia were predominantly linked with depression and psychosis impairment, respectively, rather than with specific symptoms. Cumulative trauma emerged as a bridge node associating deprivation with feelings of worthlessness and beliefs in unreal conspiracy, indicating that the experience of trauma is prominently linked with the co-occurrence of depression and psychosis symptoms related to negative views of oneself and others. These key symptoms and risk factors provide insights into the lifetime co-occurrence of depression and psychosis.

Emerging research in epigenetics has shown that there is variability in how environmental exposures “get under the skin” through mechanisms like DNA methylation to influence gene expression that may lead to differential adaptations to stress. This is the first study to examine prospectively the relationship between DNA methylation at birth and resilience to prenatal environmental stressors in several domains (conduct, hyperactivity, emotional problems, and global symptomatology) in middle childhood. We focused on DNA methylation in the vicinity of the oxytocin receptor ( OXTR ) gene as it has been previously associated with impairments in social–cognitive processes that may underlie a wide range of childhood psychopathology. Participants were 91 youth exposed to pre- and postnatal adversity with established conduct problem trajectories drawn from the Avon Longitudinal Study of Parents and Children. Consistent with our hypothesis, OXTR DNA methylation was predictive of resilience in the conduct problems domain in middle childhood. DNA methylation profiles did not predict resilience in domains of emotional, hyperactivity, and global symptomatology, suggesting a potential role for OXTR in the development of conduct problems in particular. However, individuals who were resilient to conduct problems were also broadly resilient across multiple domains. Therefore, future research should elucidate the biological pathways between OXTR DNA methylation and gene expression and its relation to impairments in social behavior.