Childhood maltreatment is associated with distinct genomic and epigenetic profiles in posttraumatic stress disorder

Abstract

Childhood maltreatment is likely to influence fundamental biological processes and engrave long-lasting epigenetic marks, leading to adverse health outcomes in adulthood. We aimed to elucidate the impact of different early environment on disease-related genomewide gene expression and DNA methylation in peripheral blood cells in patients with posttraumatic stress disorder (PTSD). Compared with the same trauma-exposed controls (n = 108), geneexpression profiles of PTSD patients with similar clinical symptoms and matched adult trauma exposure but different childhood adverse events (n = 32 and 29) were almost completely nonoverlapping (98%). These differences on the level of individual transcripts were paralleled by the enrichment of several distinct biological networks between the groups. Moreover, these gene-expression changes were accompanied and likely mediated by changes in DNA methylation in the same loci to a much larger proportion in the childhood abuse (69%) vs. the non-child abuse-only group (34%). This study is unique in providing genome-wide evidence of distinct biological modifications in PTSD in the presence or absence of exposure to childhood abuse. The findings that nonoverlapping biological pathways seem to be affected in the two PTSD groups and that changes in DNA methylation appear to have a much greater impact in the childhood-abuse group might reflect differences in the pathophysiology of PTSD, in dependence of exposure to childhood maltreatment. These results contribute to a better understanding of the extent of influence of differences in trauma exposure on pathophysiological processes in stress-related psychiatric disorders and may have implications for personalized medicine.hildhood maltreatment is a complex problem that exerts an enormous impact on individuals, families, and society, and is of great significance for public health. Maltreatment during childhood likely influences fundamental biological processes and engraves long-lasting epigenetic marks, leading to adverse health outcomes in adulthood (1). Exposure to adverse life events in childhood has not only been linked to an increased susceptibility for a number of psychiatric disorders, but also to cardiovascular disease, diabetes, and chronic lung disease, possibly via long-term influences on the immune system (2-9). This finding suggests that early adverse experiences not only alter neurobiological systems leading to an increased risk for psychiatric disorders, but may have a long-lasting effect on a number of organ systems. Experience of childhood abuse might influence these biological systems via epigenetic modifications conferring lifelong susceptibility to disease. In fact, in humans, distinct epigenetic and gene-expression changes have been observed in postmortem brains of suicide victims with a history of childhood abuse compared with suicide victims without a history of childhood abuse or control subjects (10).Early life trauma is a strong risk factor for stress-related psychiatric disorders, which themselves have been shown ...

Methylation matters: FK506 binding protein 51 (FKBP5) methylation moderates the associations ofFKBP5genotype and resistant attachment with stress regulation

“…Methylation can change the threedimensional formation of the chromatin (Li & Reinberg, 2011), and subsequently affect gene transcription. DNA methylation is thought to be influenced by prenatal (BouwlandBoth et al, 2015;Cao-Lei et al, 2014;Mychasiuk, Ilnytskyy, Kovalchuk, Kolb, & Gibb, 2011;Rijlaarsdam et al, 2017) and postnatal life events (Hughes et al, 2009;Mehta et al, 2013;Murgatroyd et al, 2009), as well as by genetic background. It can therefore be seen as the dynamic interface between genes and the environment (Meaney, 2010;Van IJzendoorn, Bakermans-Kranenburg, & Ebstein, 2011).…”

Folgen früher Traumatisierung aus neurobiologischer Sicht

“…B. Mehta et al 2013;Suderman et al 2014 (Zannas et al 2016). Genomweite Studien legen zudem nahe, dass Traumatisierungen in der Kindheit Spuren in der DNA zahlreicher Gene hinterlassen.…”

The relationship between child maltreatment and exposure to traumatic events during later adolescence and young adulthood

“…Research is increasingly identifying the links between child maltreatment and epigenetic mechanisms such as increased DNA methylation and subsequent health consequences. A recent study demonstrated that different epigenetic profiles emerged within a trauma-exposed sample with posttraumatic stress disorder (PTSD) (38), and the findings indicated that DNA methylation changes were much higher among those who had been exposed to childhood trauma. Future research should explore the influence of epigenetic mechanisms on different abuse typologies.…”