Childhood maltreatment (CM) comprises experiences of abuse and neglect during childhood. CM causes psychological as well as biological alterations in affected individuals. In humans, it is hardly explored whether these CM consequences can be transmitted directly on a biological level to the next generation. Here, we investigated the associations between maternal CM and mitochondrial bioenergetics (mitochondrial respiration and intracellular mitochondrial density) in immune cells of mothers and compared them with those of their newborns. In n = 102 healthy mother-newborn dyads, maternal peripheral blood mononuclear cells and neonatal umbilical cord blood mononuclear cells were collected and cryopreserved shortly after parturition to measure mitochondrial respiration and intracellular mitochondrial density with high-resolution respirometry and spectrophotometric analyses, respectively. Maternal CM was assessed with the Childhood Trauma Questionnaire. Maternal and neonatal mitochondrial bioenergetics were quantitatively comparable and positively correlated. Female newborns showed higher mitochondrial respiration compared to male newborns. Maternal CM load was significantly and positively associated with mitochondrial respiration and density in mothers, but not with mitochondrial respiration in newborns. Although maternal and neonatal mitochondrial bioenergetics were positively correlated, maternal CM only had a small effect on mitochondrial density in newborns, which was not significant in this study after adjustment for multiple comparisons. The biological relevance of our finding and its consequences for child development need further investigation in future larger studies. This study reports data on mitochondrial bioenergetics of healthy mother-newborn dyads with varying degrees of CM.
Background: Child maltreatment (CM) and attachment experiences are closely linked to alterations in the human oxytocin (OXT) system. However, human data about oxytocin receptor (OXTR) protein levels are lacking. Therefore, we investigated oxytocin receptor (OXTR) protein levels in circulating immune cells and related them to circulating levels of OXT in peripheral blood. We hypothesized reduced OXTR protein levels, associated with both, experiences of CM and an insecure attachment representation.Methods: OXTR protein expressions were analyzed by western blot analyses in peripheral blood mononuclear cells (PBMC) and plasma OXT levels were determined by radioimmunoassay (RIA) in 49 mothers. We used the Childhood Trauma Questionnaire (CTQ) to assess adverse childhood experiences. Attachment representations (secure vs. insecure) were classified using the Adult Attachment Projective Picture System (AAP) and levels of anxiety and depression were assessed with the German version of the Hospital Depression and Anxiety scale (HADS-D).Results: CM-affected women showed significantly lower OXTR protein expression with significantly negative correlations between the OXTR protein expression and the CTQ sum score, whereas plasma OXT levels showed no significant differences in association with CM. Lower OXTR protein expression in PBMC were particularly pronounced in the group of insecurely attached mothers compared to the securely attached group. Anxiety levels were significantly higher in CM-affected women.Conclusion: This study demonstrated a significant association between CM and an alteration of OXTR protein expression in human blood cells as a sign for chronic, long-lasting alterations in this attachment-related neurobiological system.
Background Childhood maltreatment (CM) exerts long-lasting psychological and biological alterations in affected individuals and might also affect the endocannabinoid (eCB) system which modulates inflammation and the endocrine stress response. Here, we investigated the eCB system of women with and without CM and their infants using hair samples representing eCB levels accumulated during the last trimester of pregnancy and 10–12 months postpartum. Methods CM exposure was assessed with the Childhood Trauma Questionnaire. At both timepoints, 3 cm hair strands were collected from mothers and children (N = 170 resp. 150) to measure anandamide (AEA), 2/1-arachidonoylglycerol (2-AG/1-AG), stearoylethanolamide (SEA), oleoylethanolamide (OEA), and palmitoylethanolamide (PEA). Results Maternal hair levels of 2-AG/1-AG increased and SEA levels decreased from late pregnancy to one year postpartum. Maternal CM was associated with lower SEA levels in late pregnancy, but not one year later. In the children's hair, levels of 2-AG/1-AG increased while levels of SEA, OEA, and PEA decreased from late pregnancy to one year later. Maternal CM was not consistently associated with the eCB levels measured in children's hair. Conclusions We provide first evidence for longitudinal change in the eCB system of mothers and infants from pregnancy to one year later. While maternal CM influenced the maternal eCB system, we found no consistent intergenerational effects on early regulation of the eCB system in children. Longitudinal research on the importance of the eCB system for the course and immunoregulation of pregnancy as well as for the children's development.
The neuropeptide oxytocin (OXT) and its receptor (OXTR) modulate interpersonal relationships, particularly mother–child interactions. DNA methylation (DNAm) changes of the OXTR gene were observed in individuals who experienced Childhood Maltreatment (CM). A modulatory role of single nucleotide polymorphisms (SNP) within OXTR in association with CM on the regulation of OXTR was also postulated. Whether these CM-induced epigenetic alterations are biologically inherited by the offspring remains unknown. We thus investigated possible intergenerational effects of maternal CM exposure on DNAm and OXTR gene expression, additionally accounting for the possible influence of three SNP: rs53576 and rs2254298 (OXTR gene), and rs2740210 (OXT gene). We used the Childhood Trauma Questionnaire to classify mothers into individuals with (CM+) or without CM (CM−). Maternal peripheral immune cells were isolated from venous blood (N = 117) and fetal immune cells from the umbilical cord (N = 113) after parturition. DNA methylation was assessed using MassARRAY. Taqman assays were performed for genotyping and gene expression analyses. Among mothers, CM was not associated with OXTR mean methylation or gene expression. However, four CpG sites showed different methylation levels in CM− compared to CM+. In mothers, the OXTR rs53576 and OXT rs2740210 allelic variations interacted with CM load on the OXTR mean methylation. Maternal and newborns’ mean methylation of OXTR were positively associated within CM− dyads, but not in CM+ dyads. We show gene×environment interactions on the epigenetic regulation of the oxytocinergic signaling and show the intergenerational comparability of the OXTR DNAm might be altered in infants of CM+ mothers.
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