Transgenerational Effects of Posttraumatic Stress Disorder in Babies of Mothers Exposed to the World Trade Center Attacks during Pregnancy

Yehuda, Rachel; Engel, Stephanie M.; Brand, Sarah; Seckl, Jonathan R.; Marcus, Sue M.; Berkowitz, Gertrud S.

doi:10.1210/jc.2005-0550

Cited by 638 publications

(408 citation statements)

References 20 publications

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“…We have previously suggested that parental PTSD may confer risk of PTSD in the offspring by affecting the predisposition to a modification that may later affect the response to a traumatic event (Yehuda et al, 2005;Yehuda et al, 2007a). This hypothesis is raised by the demonstration that low plasma cortisol levels in offspring are also associated particularly with maternal PTSD (Yehuda et al, 2007b).…”

Section: Discussionmentioning

confidence: 99%

“…The possibility that low cortisol in offspring was a transmitted risk factor was further supported by observations of lower salivary cortisol levels in year old infants born to mothers with PTSD compared to infants born to mothers without PTSD, following their direct exposure to the collapse of the World Trade Center on 9/11 during pregnancy (Yehuda et al, 2005). Although the contribution of paternal PTSD to cortisol levels in infant offspring was not examined, there was a significant effect of trimester (i.e., the effect was most present in the third trimester), consistent with in utero contributions to low cortisol in offspring.…”

Section: Introductionmentioning

confidence: 97%

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Maternal, not paternal, PTSD is related to increased risk for PTSD in offspring of Holocaust survivors

Yehuda

Bell

Bierer

et al. 2008

Journal of Psychiatric Research

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293

225

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Background-A significant association between parental PTSD and the occurrence of PTSD in offspring has been noted, consistent with the idea that risk for PTSD is transmitted from parent to child. Two recent reports linking maternal PTSD and low cortisol in offspring prompted us to examine the relative contributions of maternal vs. paternal PTSD in the prediction of PTSD and other psychiatric diagnoses.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Maternal, not paternal, PTSD is related to increased risk for PTSD in offspring of Holocaust survivors

Yehuda

Bell

Bierer

et al. 2008

Journal of Psychiatric Research

Self Cite

293

225

View full text Add to dashboard Cite

show abstract

“…Observations from the Dutch Famine study and others have demonstrated that parental stress may be transmitted via the gametes (Franklin et al, 2010;Dias and Ressler, 2014;Gapp et al, 2014) or the gestational uterine environment (Yehuda et al, 2005). More recently, animal work has demonstrated that variations in early maternal care (originally induced by the stress of removing mothers from pups and briefly handling the mothers before returning them to the home cage) results in altered neural, hormonal, cognitive, and behavioral responses in pups, that were not directly manipulated except for the brief separation from the mother, and the mother's behavior upon return (Liu et al, 1997;Caldji et al, 1998;Weaver et al, 2004).…”

Section: What Is the Intergenerational Transmission Of Stress?mentioning

confidence: 99%

“…This was true, even though in all cases offspring were born after World War II. It has also been shown that women who develop PTSD as a result of trauma exposure during pregnancy-such as having to evacuate the World Trade Center on 9/11-give birth to affected offspring with evidence of a trimester effect (Yehuda et al, 2005). The greater influence of maternal exposure during the third compared with second trimester provides evidence for the relevance of in utero effects to the transmission of biological risk.…”

Section: Clinical Observations and Significancementioning

confidence: 99%

Intergenerational Transmission of Stress in Humans

Bowers

Yehuda

2015

Neuropsychopharmacol

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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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“…Similarly, individuals conceived during the Dutch Hunger Winter during the Second World War showed hypomethylation at the insulinlike growth factor 2 gene (IGF2) and were more prone to obesity when tested decades later [9]. Another recently reported example is the transgenerational effects of posttraumatic stress disorder in babies of mothers exposed to the 9/11 terrorist attacks during pregnancy [10,11].…”

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confidence: 99%

Epigenetics and ncRNAs in Brain Function and Disease: Mechanisms and Prospects for Therapy

2013

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The most fundamental roles of non-coding RNAs (ncRNAs) and epigenetic mechanisms are the guidance of cellular differentiation in development and the regulation of gene expression in adult tissues. In brain, both ncRNAs and the various epigenetic gene regulatory mechanisms play a fundamental role in neurogenesis and normal neuronal function. Thus, epigenetic chromatin remodelling can render coding sites transcriptionally inactive by DNA methylation, histone modifications or antisense RNA interactions. On the other hand, microRNAs (miRNAs) are ncRNA molecules that can regulate the expression of hundreds of genes post-transcriptionally, typically recognising binding sites in the 3′ untranslated region (UTR) of mRNA transcripts. Furthermore, there are a myriad of interactions in the interface of miRNAs and epigenetics. For example, epigenetic mechanisms can silence miRNA coding sites, and miRNAs can be the effectors of transcriptional gene silencing, targeting complementary promoters or silencing the expression of epigenetic modifier genes like MECP2 and EZH2 leading to global changes in the epigenome. Alterations in this regulatory machinery play a key role in the pathology of complex disorders including cancer and neurological diseases. For example, miRNA genes are frequently inactivated by epimutations in gliomas. Here we describe the interactions between epigenetic and ncRNA regulatory systems and discuss therapeutic potential, with an emphasis on tumors, cognitive disorders and neurodegenerative diseases.

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Transgenerational Effects of Posttraumatic Stress Disorder in Babies of Mothers Exposed to the World Trade Center Attacks during Pregnancy

Abstract: The data suggest that effects of maternal PTSD related to cortisol can be observed very early in the life of the offspring and underscore the relevance of in utero contributors to putative biological risk for PTSD.

Cited by 638 publications

References 20 publications

Maternal, not paternal, PTSD is related to increased risk for PTSD in offspring of Holocaust survivors

Maternal, not paternal, PTSD is related to increased risk for PTSD in offspring of Holocaust survivors

Intergenerational Transmission of Stress in Humans

Epigenetics and ncRNAs in Brain Function and Disease: Mechanisms and Prospects for Therapy

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