Transgenerational impact of intimate partner violence on methylation in the promoter of the glucocorticoid receptor

Radtke, Karl M.; Ruf, Martina; Gunter, Helen M.; Dohrmann, Katalin; Schauer, Maggie; Meyer, Axel; Elbert, Thomas

doi:10.1038/tp.2011.21

Cited by 460 publications

(338 citation statements)

References 36 publications

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“…Fourth, information on exposure to trauma prior to treatment was not available for this sample. Traumatic experiences in childhood have been demonstrated to have lasting effects on DNA methylation of both the FKBP5 and GR genes 11, 12, 14, 15, 16, 17. Therefore, we are unable to make any conclusions regarding other environmental factors that may have influenced baseline DNA methylation and subsequent changes in DNA methylation during active treatment.…”

Section: Discussionmentioning

confidence: 86%

“…Studies of early experiences in rats found that DNA methylation of the GR promoter region was altered by maternal care, which in turn was associated with GR expression and HPA responses to stress 12. In humans, stressful life events (e.g., trauma and abuse) have been associated with higher DNA methylation at the GR promoter region13, 14, 15, 16, 17, 18 as well as differential GR expression and biological markers of HPA‐axis activity, such as salivary cortisol 13, 14. Furthermore, GR methylation has been implicated in the development of PTSD following trauma 19.…”

Section: Introductionmentioning

confidence: 99%

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Hpa Axis Related Genes and Response to Psychological Therapies: Genetics and Epigenetics

et al. 2015

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BackgroundHypothalamic–pituitary–adrenal (HPA) axis functioning has been implicated in the development of stress‐related psychiatric diagnoses and response to adverse life experiences. This study aimed to investigate the association between genetic and epigenetics in HPA axis and response to cognitive behavior therapy (CBT).MethodsChildren with anxiety disorders were recruited into the Genes for Treatment project (GxT, N = 1,152). Polymorphisms of FKBP5 and GR were analyzed for association with response to CBT. Percentage DNA methylation at the FKBP5 and GR promoter regions was measured before and after CBT in a subset (n = 98). Linear mixed effect models were used to investigate the relationship between genotype, DNA methylation, and change in primary anxiety disorder severity (treatment response).ResultsTreatment response was not associated with FKBP5 and GR polymorphisms, or pretreatment percentage DNA methylation. However, change in FKBP5 DNA methylation was nominally significantly associated with treatment response. Participants who demonstrated the greatest reduction in severity decreased in percentage DNA methylation during treatment, whereas those with little/no reduction in severity increased in percentage DNA methylation. This effect was driven by those with one or more FKBP5 risk alleles, with no association seen in those with no FKBP5 risk alleles. No significant association was found between GR methylation and response.ConclusionsAllele‐specific change in FKBP5 methylation was associated with treatment response. This is the largest study to date investigating the role of HPA axis related genes in response to a psychological therapy. Furthermore, this is the first study to demonstrate that DNA methylation changes may be associated with response to psychological therapies in a genotype‐dependent manner.

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Section: Discussionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Hpa Axis Related Genes and Response to Psychological Therapies: Genetics and Epigenetics

et al. 2015

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“…A positive association was observed between methylation status of the NR3C1 promoter in offspring at 10-19 years of age and maternal exposure to intimate partner violence (IPV) during pregnancy (Radtke et al, 2011). A positive correlation was also found between maternal prenatal stress associated with living in the Democratic Republic of Congo, a region plagued by ongoing war and violence, and newborn methylation in the promoter of NR3C1 in umbilical cord blood (Mulligan et al, 2012).…”

Section: Epigeneticsmentioning

confidence: 90%

Intergenerational Transmission of Stress in Humans

Bowers

Yehuda

2015

Neuropsychopharmacol

409

269

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The hypothesis that offspring are affected by parental trauma or stress exposure, first noted anecdotally, is now supported empirically by data from Holocaust survivor offspring cohorts and other populations. These findings have been extended to less extreme forms of stress, where differential physical, behavioral, and cognitive outcomes are observed in affected offspring. Parental stress-mediated effects in offspring could be explained by genetics or social learning theory. Alternatively, biological variations stemming from stress exposure in parents could more directly have an impact on offspring, a concept we refer to here as 'intergenerational transmission', via changes to gametes and the gestational uterine environment. We further extend this definition to include the transmission of stress to offspring via early postnatal care, as animal studies demonstrate the importance of early maternal care of pups in affecting offsprings' long-term behavioral changes. Here, we review clinical observations in offspring, noting that offspring of stress-or trauma-exposed parents may be at greater risk for physical, behavioral, and cognitive problems, as well as psychopathology. Furthermore, we review findings concerning offspring biological correlates of parental stress, in particular, offspring neuroendocrine, epigenetic, and neuroanatomical changes, in an attempt to determine the extent of parental stress effects. Although understanding the etiology of effects in offspring is currently impeded by methodological constraints, and limitations in our knowledge, we summarize current information and conclude by presenting hypotheses that have been prompted by recent studies in the field.

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“…Precisely, the NR3C1 locus was found to be hypermethylated in children whose mothers suffered from depression and anxiety during the third trimester of their pregnancy (51). Women's experience of intimate partner violence during pregnancy also has been associated with increased NR3C1 methylation in their adolescent offspring (52). When women were exposed to the Tutsi genocide during pregnancy, their children had higher methylation of the NR3C1 exon 1F than offspring from nonexposed women (53).…”

Section: Discussionmentioning

confidence: 99%

Prenatal loss of father during World War One is predictive of a reduced lifespan in adulthood

Todd

Valleron

Bougnères

2017

Proc. Natl. Acad. Sci. U.S.A.

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Although early-life stress is known to alter health, its long-term consequences on mortality remain largely unknown. Thanks to unique French legislation established in 1917 for war orphans and children of disabled soldiers, we were able to study the adult mortality of individuals born in 1914–1916 whose fathers were killed during World War 1. Vital information and socio-demographic characteristics were extracted manually from historical civil registers for 5,671 children born between 1 August 1914 and 31 December 1916 who were granted the status of “pupille de la Nation” (orphan of the Nation). We used a database comprising 1.4 million deceased soldiers to identify war orphans and collect information on their fathers and then paired each orphan with a nonorphan from the same birth register matched for date of birth, sex, and mother’s age at the infant’s birth. Mortality between ages 31 and 99 y was analyzed for 2,365 orphan/nonorphan pairs. The mean loss of adult lifespan of orphans who had lost their father before birth was 2.4 y (95% CI: 0.7, 3.9 y) and was the result of increased mortality before age 65 y. Adult lifespan was not reduced when the father’s death occurred after the infant’s birth. These results support the notion that intrauterine exposure to a major psychological maternal stress can affect human longevity.

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Transgenerational impact of intimate partner violence on methylation in the promoter of the glucocorticoid receptor

Cited by 460 publications

References 36 publications

Hpa Axis Related Genes and Response to Psychological Therapies: Genetics and Epigenetics

Hpa Axis Related Genes and Response to Psychological Therapies: Genetics and Epigenetics

Intergenerational Transmission of Stress in Humans

Prenatal loss of father during World War One is predictive of a reduced lifespan in adulthood

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