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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.

Oxytocin has been a hormone of interest in understanding both depression and parenting. Here, the role of oxytocin has been explored in understanding the interaction between perinatal depression, history of trauma and subsequent longer-term child socio-emotional outcomes. Data were obtained from 203 pregnant women from the Mercy Pregnancy and Emotional Wellbeing Study (MPEWS), a pregnancy cohort study with data collected across pregnancy, postpartum and until 4 years for mother and child. Maternal antenatal depression was measured using the Structured Clinical Interview for DSM-IV (SCID-IV) together with the Childhood Trauma Questionnaire to measure maternal trauma history. Maternal oxytocin levels were measured by enzyme immunoassay following extraction at four time points across pregnancy and the postpartum. The offspring consisted of 203 children followed up from birth until 4 years of age when they were assessed for DSM 5 depression and anxiety disorders (emotional disorders) using the Preschool Age Psychiatric Assessment. Maternal oxytocin levels increased over pregnancy and the postpartum in both control and depressed women with no difference between groups. Maternal childhood trauma and antenatal antidepressant use was also not associated with maternal oxytocin levels. Lower gestational age, maternal depression and early childhood trauma, and late pregnancy oxytocin concentrations were associated with later childhood emotional disorders; together they predicted 10% of variance for emotional disorders. Oxytocin is a hormone whose role in understanding intergenerational risk from pregnancy to child emotional disorders is dependent on relational context. Future research can expand on understanding these important early predictors of childhood mental health., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Oxytocin is associated with the establishment and quality of maternal behavior in animal models. Parallel investigations in humans are now under way. This article reviews the current research examining the role of oxytocin in mother-infant relations, attachment, and bonding in humans., Methods: A systematic search was made of three electronic databases and other bibliographic sources for published research studies that examined oxytocin and mother-infant relations in humans, including attachment, maternal behavior, parenting, and mother-infant relations., Results: Eight studies were identified, all of which were unique in their methodologies, populations studied, and measures used. Seven studies found significant and strong associations between levels or patterns of oxytocin and aspects of mother-infant relations or attachment., Conclusions: Oxytocin appears to be of crucial importance for understanding mother-infant relationships. The findings of this review suggest that the pioneering, but preliminary, research undertaken to date is promising and that replication with larger samples is needed. Research that draws on more robust measures of attachment and bonding, as well as improved measures of oxytocin that include both central and peripheral levels, will elucidate the role of oxytocin in human mother-infant relationships. As the production of oxytocin is by no means restricted to mothers, the extension of the oxytocin studies to fathering, as well as to alloparental caregiving, would be an intriguing next step.