Psychiatric symptoms are interrelated and found to be largely captured by a general psychopathology factor (GPF). Although epigenetic mechanisms, such as DNA methylation (DNAm), have been linked to... Show morePsychiatric symptoms are interrelated and found to be largely captured by a general psychopathology factor (GPF). Although epigenetic mechanisms, such as DNA methylation (DNAm), have been linked to individual psychiatric outcomes, associations with GPF remain unclear. Using data from 440 children aged 10 years participating in the Generation R Study, we examined the associations of DNAm with both general and specific (internalizing, externalizing) factors of psychopathology. Genome-wide DNAm levels, measured in peripheral blood using the Illumina 450K array, were clustered into wider co-methylation networks ('modules') using a weighted gene co-expression network analysis. One co-methylated module associated with GPF after multiple testing correction, while none associated with the specific factors. This module comprised of 218 CpG probes, of which 198 mapped onto different genes. The CpG most strongly driving the association with GPF was annotated to FZD1, a gene that has been implicated in schizophrenia and wider neurological processes. Associations between the probes contained in the co-methylated module and GPF were supported in an independent sample of children from the Avon Longitudinal Study of Parents and Children (ALSPAC), as evidenced by significant correlations in effect sizes. These findings might contribute to improving our understanding of dynamic molecular processes underlying complex psychiatric phenotypes. Show less
DNA methylation (DNAm) is known to play a pivotal role in childhood health and development, but a comprehensive characterization of genome-wide DNAm trajectories across this age period is currently... Show moreDNA methylation (DNAm) is known to play a pivotal role in childhood health and development, but a comprehensive characterization of genome-wide DNAm trajectories across this age period is currently lacking. We have therefore performed a series of epigenome-wide association studies in 5019 blood samples collected at multiple time-points from birth to late adolescence from 2348 participants of two large independent cohorts. DNAm profiles of autosomal CpG sites (CpGs) were generated using the Illumina Infinium HumanMethylation450 BeadChip. Change over time was widespread, observed at over one-half (53%) of CpGs. In most cases, DNAm was decreasing (36% of CpGs). Inter-individual variation in linear trajectories was similarly widespread (27% of CpGs). Evidence for non-linear change and inter-individual variation in non-linear trajectories was somewhat less common (11 and 8% of CpGs, respectively). Very little inter-individual variation in change was explained by sex differences (0.4% of CpGs) even though sex-specific DNAm was observed at 5% of CpGs. DNAm trajectories were distributed non-randomly across the genome. For example, CpGs with decreasing DNAm were enriched in gene bodies and enhancers and were annotated to genes enriched in immune-developmental functions. In contrast, CpGs with increasing DNAm were enriched in promoter regions and annotated to genes enriched in neurodevelopmental functions. These findings depict a methylome undergoing widespread and often non-linear change throughout childhood. They support a developmental role for DNA methylation that extends beyond birth into late adolescence and has implications for understanding life-long health and disease. DNAm trajectories can be visualized at http://epidelta.mrcieu. ac.uk. Show less
The underlying mechanisms of paternal responses to infant signals are poorly understood. Vasopressin has previously been proposed to affect these responses. Using a double-blind, placebo-controlled... Show moreThe underlying mechanisms of paternal responses to infant signals are poorly understood. Vasopressin has previously been proposed to affect these responses. Using a double-blind, placebo-controlled, within-subject design (N = 25 expectant fathers), we examined the effect of vasopressin administration on the use of excessive handgrip force during exposure to infant crying versus matched control sounds, while participants saw morphed images representing their own infant versus an unknown infant. We found that, compared to placebo, AVP administration elicited more excessive force while viewing an unknown infant image compared to viewing the image representing one’s own infant, while the reverse was true under placebo. The results are discussed in light of vasopressin’s role in parenting and parental protection among human fathers. Show less
Cao, C.; Rijlaarsdam, J.; Voort, A. van der; Ji, L.; Zhang, W.; Bakermans-Kranenburg, M.J. 2018
Family adversity has been associated with children's bullying behaviors. The evidence is, however, dominated by mothers' perceptions of the family environment and a focus on mothers' behaviors.... Show moreFamily adversity has been associated with children's bullying behaviors. The evidence is, however, dominated by mothers' perceptions of the family environment and a focus on mothers' behaviors. This prospective population-based study examined whether children's bullying behaviors were associated with mother- and father-reported family adversity, assessed before and after child birth. Peer-nominations were used to assess bullying behaviors of 1298 children in elementary school (mean age 7.5 years). The following paternal risk factors were prospectively associated with children's bullying behaviors: (1) father-reported prenatal family distress, (2) fathers' hostility at preschool age, and (3) fathers' harsh disciplinary practices at preschool age, but effect sizes were relatively small. The effect of maternal risk factors was less consistent, only mother-reported family distress in childhood was associated with children's bullying behaviors. The associations were independent of background family risk factors (i.e., life stress, contextual factors, and other background factors such as parental education and risk taking record) and early childhood externalizing problems. Moreover, our results indicated that father-reported family adversity predicted children's bullying behaviors over and above the background family risk factors, early childhood externalizing problems and mother-reported family adversity. We also demonstrated that the association of fathers' prenatal hostility and family distress with subsequent bullying behavior of their child at school was partly mediated by fathers' harsh disciplinary practices at preschool age. Our findings highlight the importance of fathers' behaviors in the development of children's bullying behaviors. Show less
BackgroundConduct problems (CP) and attention deficit hyperactivity disorder (ADHD) are often comorbid and have each been linked to ‘unhealthy diet’. Early‐life diet also associates with DNA... Show moreBackgroundConduct problems (CP) and attention deficit hyperactivity disorder (ADHD) are often comorbid and have each been linked to ‘unhealthy diet’. Early‐life diet also associates with DNA methylation of the insulin‐like growth factor 2 gene (IGF2), involved in fetal and neural development. We investigated the degree to which prenatal high‐fat and ‐sugar diet might relate to ADHD symptoms via IGF2 DNA methylation for early‐onset persistent (EOP) versus low CP youth. MethodsParticipants were 164 youth with EOP (n = 83) versus low (n = 81) CP drawn from the Avon Longitudinal Study of Parents and Children. We assessed if the interrelationships between high‐fat and ‐sugar diet (prenatal, postnatal), IGF2 methylation (birth and age 7, collected from blood), and ADHD symptoms (age 7–13) differed for EOP versus low CP youth. ResultsPrenatal ‘unhealthy diet’ was positively associated with IGF2 methylation at birth for both the EOP and low CP youth. For EOP only: (a) higher IGF2 methylation predicted ADHD symptoms; and (b) prenatal ‘unhealthy diet’ was associated with higher ADHD symptoms indirectly via higher IGF2 methylation. ConclusionsPreventing ‘unhealthy diet’ in pregnancy might reduce the risk of ADHD symptoms in EOP youth via lower offspring IGF2 methylation. Show less
