Association between DNA methylation and ADHD symptoms from birth to school age: A prospective meta-analysis

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

Epigenetics applied to child and adolescent mental health: Progress, challenges and opportunities

BACKGROUND: Epigenetic processes are fast emerging as a promising molecular system in the search for both biomarkers and mechanisms underlying human health and disease risk, including psychopathology. METHODS: In this review, we discuss the application of epigenetics (specifically DNA methylation) to research in child and adolescent mental health, with a focus on the use of developmentally sensitive datasets, such as prospective, population-based cohorts. We look back at lessons learned to date, highlight current developments in the field and areas of priority for future research. We also reflect on why epigenetic research on child and adolescent mental health currently lags behind other areas of epigenetic research and what we can do to overcome existing barriers. RESULTS: To move the field forward, we advocate for the need of large-scale, harmonized, collaborative efforts that explicitly account for the time-varying nature of epigenetic and mental health data across development. CONCLUSION: We conclude with a perspective on what the future may hold in terms of translational applications as more robust signals emerge from epigenetic research on child and adolescent mental health

Epigenetics applied to child and adolescent mental health: Progress, challenges and opportunities

BackgroundEpigenetic processes are fast emerging as a promising molecular system in the search for both biomarkers and mechanisms underlying human health and disease risk, including psychopathology.MethodsIn this review, we discuss the application of epigenetics (specifically DNA methylation) to research in child and adolescent mental health, with a focus on the use of developmentally sensitive datasets, such as prospective, population-based cohorts. We look back at lessons learned to date, highlight current developments in the field and areas of priority for future research. We also reflect on why epigenetic research on child and adolescent mental health currently lags behind other areas of epigenetic research and what we can do to overcome existing barriers.ResultsTo move the field forward, we advocate for the need of large-scale, harmonized, collaborative efforts that explicitly account for the time-varying nature of epigenetic and mental health data across development.ConclusionWe conclude with a perspective on what the future may hold in terms of translational applications as more robust signals emerge from epigenetic research on child and adolescent mental health

Mapping 2007-08 Tuition And Fees In Higher Education

Using data sets from US News & World Report and the Association to Advance Collegiate Schools of Business, this paper isolates 10 factors that account for 90 percent of the variation in tuition and fees across 523 institutions of higher learning in the United States.  It is hoped that the results will give guidance to schools by quantifying the costs and benefits of making a given change to their tuition and fee structure.&nbsp

Epigenetic signatures of childhood abuse and neglect:Implications for psychiatric vulnerability

Childhood maltreatment is a key risk factor for poor mental and physical health. Recently, variation in epigenetic processes, such as DNA methylation, has emerged as a potential pathway mediating this association; yet, the extent to which different forms of maltreatment may be characterized by unique vs shared epigenetic signatures is currently unknown. In this study, we quantified DNA methylation across the genome in buccal epithelial cell samples from a high-risk sample of inner-city youth (n = 124; age = 16-24; 53% female), 68% of whom reported experiencing at least one form of maltreatment while growing up. Our analyses aimed to identify methylomic variation associated with exposure to five major types of childhood maltreatment. We found that: (i) maltreatment types differ in the extent to which they associate with methylomic variation, with physical exposures showing the strongest associations; (ii) many of the identified loci are annotated to genes previously implicated in stress-related outcomes, including psychiatric and physical disorders (e.g. GABBR1, GRIN2D, CACNA2D4, PSEN2); and (iii) based on gene ontology analyses, maltreatment types not only show unique methylation patterns enriched for specific biological processes (e.g. physical abuse and cardiovascular function), but also share a ‘common’ epigenetic signature enriched for biological processes related to neural development and organismal growth. A stringent set of sensitivity analyses were also run to identify high-confidence associations. Together, findings lend novel insights into epigenetic signatures of childhood abuse and neglect, point to novel potential biomarkers for future investigation and support a molecular link between maltreatment and poor health outcomes. Nevertheless, it will be important in future to replicate findings, as the use of cross-sectional data and high rates of polyvictimization in our study make it difficult to fully disentangle the shared vs unique epigenetic signatures of maltreatment types. Furthermore, studies will be needed to test the role of potential moderators in the identified associations, including age of onset and chronicity of maltreatment exposure. <br/

Using Openly Accessible Resources to Strengthen Causal Inference in Epigenetic Epidemiology of Neurodevelopment and Mental Health

The recent focus on the role of epigenetic mechanisms in mental health has led to several studies examining the association of epigenetic processes with psychiatric conditions and neurodevelopmental traits. Some studies suggest that epigenetic changes might be causal in the development of the psychiatric condition under investigation. However, other scenarios are possible, e.g., statistical confounding or reverse causation, making it particularly challenging to derive conclusions on causality. In the present review, we examine the evidence from human population studies for a possible role of epigenetic mechanisms in neurodevelopment and mental health and discuss methodological approaches on how to strengthen causal inference, including the need for replication, (quasi-)experimental approaches and Mendelian randomization. We signpost openly accessible resources (e.g., &ldquo;MR-Base&rdquo; &ldquo;EWAS catalog&rdquo; as well as tissue-specific methylation and gene expression databases) to aid the application of these approaches