Childhood maltreatment (CM) is an established major risk factor for a number of negative health outcomes later in life. While epigenetic mechanisms, such as DNA methylation (DNAm), have been proposed as a means of embedding this environmental risk factor, little is known about its timing and trajectory, especially in very young children. It is also not clear whether additional environmental adversities, often experienced by these children, converge on similar DNAm changes. Here, we calculated a cumulative adversity score, which additionally to CM includes socioeconomic status (SES), other life events, parental psychopathology and epigenetic biomarkers of prenatal smoking and alcohol consumption. We investigated the effects of CM alone as well as the adversity score on longitudinal DNAm trajectories in the Berlin Longitudinal Child Study. This is a cohort of 173 children aged 3–5 years at baseline of whom 86 were exposed to CM. These children were followed-up for 2 years with extensive psychometric and biological assessments as well as saliva collection at 5 time points providing genome-wide DNAm levels. Overall, only a few DNAm patterns were stable over this timeframe, but less than 10 DNAm regions showed significant changes. At baseline, neither CM nor the adversity score associated with DNAm changes. However, in 6 differentially methylated regions (DMRs), CM and the adversity score significantly moderated DNAm trajectories over time. A number of these DMRs have previously been associated with adverse prenatal exposures. In our study, children exposed to CM also presented with epigenetic signatures indicative of increased prenatal exposure to tobacco and alcohol, as compared to non-CM exposed children. These epigenetic signatures of prenatal exposure strongly correlate with DNAm regions associated with CM and the adversity score. Finally, weighted correlation network analysis revealed a module of CpGs exclusively associated with CM. While our study identifies DNAm loci specifically associated with CM, especially within long non-coding RNAs, the majority of associations were found with the adversity score with convergent association with indicators of adverse prenatal exposures. This study highlights the importance of mapping not only of the epigenome but also the exposome and extending the observational timeframe to well before birth.

Lasting effects of adversity, such as exposure to childhood adversity (CA) on disease risk, may be embedded via epigenetic mechanisms but findings from human studies investigating the main effects of such exposure on epigenetic measures, including DNA methylation (DNAm), are inconsistent. Studies in perinatal tissues indicate that variability of DNAm at birth is best explained by the joint effects of genotype and prenatal environment. Here, we extend these analyses to postnatal stressors. We investigated the contribution of CA, cis genotype (G), and their additive (G + CA) and interactive (G × CA) effects to DNAm variability in blood or saliva from five independent cohorts with a total sample size of 1074 ranging in age from childhood to late adulthood. Of these, 541 were exposed to CA, which was assessed retrospectively using self-reports or verified through social services and registries. For the majority of sites (over 50%) in the adult cohorts, variability in DNAm was best explained by G + CA or G × CA but almost never by CA alone. Across ages and tissues, 1672 DNAm sites showed consistency of the best model in all five cohorts, with G × CA interactions explaining most variance. The consistent G × CA sites mapped to genes enriched in brain-specific transcripts and Gene Ontology terms related to development and synaptic function. Interaction of CA with genotypes showed the strongest contribution to DNAm variability, with stable effects across cohorts in functionally relevant genes. This underscores the importance of including genotype in studies investigating the impact of environmental factors on epigenetic marks.

We investigated peripheral blood mononuclear cell gene expression responses to acute psychosocial stress to identify molecular pathways relevant to the stress response. Blood samples were obtained from 10 healthy male subjects before, during and after (at 0, 30, and 60 min) a standardized psychosocial laboratory stressor. Ribonucleic acid (RNA) was extracted and gene expression measured by hybridization to a 20,000-gene microarray. Gene Set Expression Comparisons (GSEC) using defined pathways were used for the analysis. Forty-nine pathways were significantly changed from baseline to immediately after the stressor (p < 0.05), implicating cell cycle, cell signaling, adhesion and immune responses. The comparison between stress and recovery (measured 30 min later) identified 36 pathways, several involving stress-responsive signaling cascades and cellular defense mechanisms. These results have relevance for understanding molecular mechanisms of the physiological stress response, and might be used to further study adverse health outcomes of psychosocial stress.

Despite common notion that the correlation of socioeconomic status with child cognitive performance may be driven by both environmentally– and genetically–mediated transactional pathways, there is a lack of longitudinal and genetically informed research that examines these postulated associations. The present study addresses whether family income predicts associative memory growth and hippocampal development in middle childhood and tests whether these associations persist when controlling for DNA–based polygenic scores of educational attainment. Participants were 142 6–to–7–year–old children, of which 127 returned when they were 8–to–9 years old. Longitudinal analyses indicated that the association of family income with children's memory performance and hippocampal volume remained stable over this age range and did not predict change. On average, children from economically disadvantaged background showed lower memory performance and had a smaller hippocampal volume. There was no evidence to suggest that differences in memory performance were mediated by differences in hippocampal volume. Further exploratory results suggested that the relationship of income with hippocampal volume and memory in middle childhood is not primarily driven by genetic variance captured by polygenic scores of educational attainment, despite the fact that polygenic scores significantly predicted family income.

Chronic fatigue syndrome (CFS) is a common and debilitating illness [1]. As yet the pathophysiology of CFS remains inchoate, so pharmacologic management aims to alleviate symptoms and is not curative. Cognitive-behavioral therapy and graded exercise therapy appear to be the most effective treatments for CFS [2]. Such therapies require that patients understand, adhere to and practice specific activities to manage their thoughts and expenditure of physical energy. This necessary understanding and commitment are heavily impacted by patients’ coping styles and concomitant psychopathology. In a previous population-based study, we found that people with CFS were significantly more likely to use maladaptive everyday coping strategies than non-fatigued matched controls [3]. In another population-based study, we found that about 60% of people with CFS suffered psychiatric comorbidity; in particular affective and anxiety disorders [4], and displayed maladaptive personality styles [5]. In the current population-based study, we examined coping styles in CFS and how these are affected by depression and anxiety.

Aims: Recent research has revealed that early life trauma (ELS), including abuse (sexual and/or physical) and neglect, produce lasting changes in the CNS. We posited that cognitive deficits, often observed in psychiatric patients, result, in part, due to the neurobiological consequences of ELS. Additionally, we hypothesized that the nature and magnitude of cognitive deficits would differ according to the subtype of ELS experienced. Method: The Cambridge Neuropsychological Test Automated Battery (CANTAB) was used to assess neurocognitive functioning in 93 subjects (60 with ELS and 33 without). In the patients with a history of ELS, 35% and 16.7%, respectively, met criteria for current major depression and PTSD. Results: Significant associations between ELS status and CANTAB measures of memory and executive and emotional functioning were found. Conclusions: These data suggest that exposure to ELS results in a cascade of neurobiological changes associated with cognitive deficits in adulthood that vary according to the type of trauma experienced.