The Tutsi genocide and transgenerational transmission of maternal stress: epigenetics and biology of the HPA axis

Perroud, Nader; Rutembesa, Eugène; Paoloni-Giacobino, Ariane; Mutabaruka, Jean; Mutesa, Léon; Stenz, Ludwig; Malafosse, Alain; Karege, Félicien

doi:10.3109/15622975.2013.866693

Cited by 267 publications

(173 citation statements)

References 38 publications

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“…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). NR3C1 is not the only locus where DNA methylation is modified by maternal stress.…”

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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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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“…Perroud et al similarly found hypermethylation of the NR3C1 promoter in offspring born to Tutsi widows pregnant during the genocide of ethnic Tutsis in Rwanda (Perroud et al, 2014). However, another study has reported that there is a nonsignificant effect of perinatal stress, defined as the sum of maternal psychological problems during pregnancy or the 3 months after delivery, on NR3C1 methylation in adolescent offspring (van der Knaap et al, 2014).…”

Section: Epigeneticsmentioning

confidence: 99%

Intergenerational Transmission of Stress in Humans

Bowers

Yehuda

2015

Neuropsychopharmacol

379

260

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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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“…Moreover, exposed mothers and their children had higher methylation of the NR3C1 exon 1F than nonexposed groups and exposed mothers showed higher methylation of CpGs located within the NR3C2 coding sequence than nonexposed mothers (Perroud et al. 2014). Therefore, this research emphasized that transgenerational impact of a trauma is a reality not only from a clinical point of view but also from a biological one.…”

Section: Genetic Services In Rwandamentioning

confidence: 99%

Medical genetics and genomic medicine in Rwanda

Uwineza

Mutesa

2015

Molec Gen & Gen Med

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The Tutsi genocide and transgenerational transmission of maternal stress: epigenetics and biology of the HPA axis

Abstract: PTSD was associated with NR3C1 epigenetic modifications that were similarly found in the mothers and their offspring, modifications that may underlie the possible transmission of biological alterations of the HPA axis.

Cited by 267 publications

References 38 publications

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

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

Intergenerational Transmission of Stress in Humans

Medical genetics and genomic medicine in Rwanda

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