Stress, particularly when experienced early in life, can have profound implications for mental health. Previous research covering various tissues such as the brain, suggests that the detrimental impact of early-life stress (ELS) on mental health is mediated via epigenetic modifications including DNA methylation. Genes of the hypothalamic–pituitary–adrenal axis—in particular, the glucocorticoid receptor (hGR) gene—stand out as key targets for ELS. Even though the link between hGR methylation and either ELS or psychopathology is fairly well established, the mutually dependent relationships between ELS, DNA methylation and psychopathology remain to be uncovered. The specific psychopathology an individual might develop in the aftermath of stressful events can be highly variable, however, most studies investigating hGR methylation and psychopathology suffer from being limited to a single symptom cluster of mental disorders. Here, we screened volunteers for childhood maltreatment and analyzed whether it associates with hGR methylation in lymphocytes and a range of measures of psychological ill-health. hGR methylation in lymphocytes most likely reflects methylation patterns found in the brain and thus provides valuable insights into the etiology of psychopathology. We find the interaction between childhood maltreatment and hGR methylation to be strongly correlated with an increased vulnerability to psychopathology providing evidence of epigenome × environment interactions. Furthermore, our results indicate an additive effect of childhood maltreatment and hGR methylation in predicting borderline personality disorder (BPD)-associated symptoms, suggesting that the combination of both ELS and DNA methylation that possibly represents unfavorable events experienced even earlier in life poses the risk for BPD.

Research has shown the harmful potential of institutional care on young children; however, little is known about the consequences of institutional care on infants in Sub-Saharan Africa. We compared 35 Tanzanian children who were institutionalized at birth to 4 years of age with a matched group of 35 children who were institutionalized at 5 to 14 years of age. We examined adverse childhood experiences over the course of their entire lives, in their family of origin and in institutional care, and mental health problems at primary school age, such as depressive symptoms, aggressive behavior, and internalizing and externalizing problems. Results showed that early institutionalized children reported more adverse experiences during their time in institutional care and a greater variety of mental health problems than did late institutionalized children. Moreover, maltreatment in institutional care was positively related to mental health problems only in early institutionalized children. We conclude that adverse experiences in institutional care play an important role for early institutionalized children who need special care from adequately educated caregivers. Therefore, training concepts focusing on the needs of the youngest children have to be developed, tested, and established. Countries such as Tanzania need policies that apply to all orphanages to ensure an adequate standard of quality in childcare.

Background: Previous research reveals an association between traumatic stress and an increased risk for numerous diseases, including cancer. At the molecular level, stress may increase carcinogenesis via increased DNA damage and impaired DNA repair mechanisms. We assessed DNA breakage in peripheral blood mononuclear cells from individuals with post-traumatic stress disorder (PTSD) and measured the cellular capacity to repair single-strand breaks after exposure to ionizing X-radiation. We also investigated the effect of psychotherapy on both DNA breakage and DNA repair. Methods: In a first study we investigated DNA breakage and repair in 34 individuals with PTSD and 31 controls. Controls were subdivided into 11 trauma-exposed subjects and 20 individuals without trauma exposure. In a second study, we analysed the effect of psychotherapy (Narrative Exposure Therapy) on DNA breakage and repair. Thirty-eight individuals with PTSD were randomly assigned to either a treatment or a waitlist control condition. Follow-up was performed 4 months and 1 year after therapy. Results: In study 1 we found higher levels of basal DNA breakage in individuals with PTSD and trauma-exposed subjects than in controls, indicating that traumatic stress is associated with DNA breakage. However, single-strand break repair was unimpaired in individuals with PTSD. In study 2, we found that psychotherapy reversed not only PTSD symptoms, but also DNA strand break accumulation. Conclusion: Our results show - for the first time in vivo - an association between traumatic stress and DNA breakage; they also demonstrate changes at the molecular level, i.e., the integrity of DNA, after psychotherapeutic interventions.

BackgroundAnecdotal evidence suggests the frequently traumatic nature of female genital mutilation (FGM). At present, systematic research on the psychological sequelae of this tradition has remained limited. The study provides preliminary, high-quality psychodiagnostic data on potential psychopathological consequences of FGM, with a focus on posttraumatic stress disorder (PTSD), shutdown dissociation and other stress-related variables.MethodsWe investigated a convenience sample of N = 167 women, supported by the women’s affairs headquarters in Jijiga (capital of the Ethiopian Somali Region) and a local Ethiopian non-governmental organization. Our main outcome measures were PTSD (PSS-I) and shutdown dissociation (ShuD). We also assessed depression and anxiety (HSCL-25), major depression, substance abuse and dependence, suicidality and psychotic disorders (M.I.N.I.; sub-scales A., B., K., and L.). In addition, we collected hair samples to assess hair cortisol concentrations (HCC) as a neuroendocrinological measure.ResultsThe majority of women endured FGM (FGM I: 36%, FGM II/III: 52%) and, regardless of the level of the physical invasiveness, almost all women reported having felt intense fear and/or helplessness. FGM II/III, the more invasive form, was associated with a greater vulnerability to PTSD symptoms (p < .001) and shutdown dissociation (p < .001). Symptoms of depression (p < .05) and anxiety (p < .01) were also elevated. Random forest regression with conditional inference trees revealed evidence of an alteration of the cortisol levels in relation to the age when FGM was experienced (< 1 year) and the invasiveness of the procedure.ConclusionMore extensive forms of FGM are associated with more severe psychopathological symptoms – particularly with an increased vulnerability to PTSD. Higher hair cortisol levels in women who experienced FGM before their first year of age or had more severe forms of FGM indicate long-term neuroendocrinological consequences of FGM and trauma in general on the stress system.