Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation

Yehuda, Rachel; Daskalakis, Nikolaos P.; Bierer, Linda M.; Bader, Heather N.; Klengel, Torsten; Holsboer, Florian; Binder, Elisabeth B.

doi:10.1016/j.biopsych.2015.08.005

Cited by 569 publications

(428 citation statements)

References 56 publications

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“…The idea that intergenerational stress transmission is adaptive for offspring might explain findings where parents and offspring had opposite biological correlates of parental stress. For instance, Holocaust survivors exhibited inverse 11β-HSD2 activity and FKBP5 methylation compared with their offspring Bierer et al, 2014;Yehuda et al, 2015). If these original effects in parents reflect exposure to extreme stress, perhaps opposite marks or activity in offspring are intended to promote resilience in a similar context.…”

Section: Discussionmentioning

confidence: 99%

Intergenerational Transmission of Stress in Humans

Bowers

Yehuda

2015

Neuropsychopharmacol

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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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Section: Discussionmentioning

confidence: 99%

Intergenerational Transmission of Stress in Humans

Bowers

Yehuda

2015

Neuropsychopharmacol

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394

269

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“…More recent evidence shows that the offspring of male mice, who consumed a low protein diet during late childhood (from weaning until sexual maturity), have elevated expression of many genes in liver tissue and exhibit changes in cytosine methylation (Carone et al, 2010). Similarly, it has been shown that the offspring of Holocaust survivors had altered gene expression levels related to cortisol (Yehuda, 2015). Many studies argue that the most likely mechanism behind such phenomena are environmentally induced but heritable changes in the epigenome (Morgan et al, 1999, Rakyan et al, 2003, Ng et al, 2010.…”

Section: Introductionmentioning

confidence: 99%

Transgenerational effects of childhood conditions on third generation health and education outcomes

Berg

Pinger

2016

Economics & Human Biology

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General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Phone: +49-621-181-1923; Fax: +49-228-73-9239. AbstractThis paper examines the extent to which pre-puberty nutritional conditions in one generation affect productivity-related outcomes in later generations. Recent findings from the biological literature suggest that the so-called slow growth period around age 9 is a sensitive period for male germ cell development. We build on this evidence and investigate whether undernutrition at those ages transmits to children and grandchildren. Our findings indicate that third generation males (females) tend to have higher mental health scores if their paternal grandfather (maternal grandmother) was exposed to a famine during the slow growth period. These effects appear to reflect biological responses to adaptive expectations about scarcity in the environment, and as such they can be seen as an economic correctional mechanism in evolution, with marked socio-economic implications for the offspring.

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“…Stress-and well-being-related methylation signals may be passed on from one generation to the next. The methylation of FKBP5, an important regulator of the glucocorticoid receptor, was recently found to be altered both in holocaust survivors and their adult offspring, pointing to a transgenerational effect of preconception parental trauma (Yehuda et al 2016). …”

Section: A Third Research Question Is About the Molecular Mechanisms mentioning

confidence: 99%

Happiness and its molecular fingerprints

Probst‐Hensch

2017

Int Rev Econ

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Happiness and well-being are in part heritable, but modifiable traits. The promotion of well-being and happiness, much like the primary prevention of noncommunicable diseases (NCD), will become increasingly important in a world that is facing an NCD epidemic due to demographic aging and urbanization. The costs for the often lifelong treatment of NCDs are already high and may increase further with the arrival of expensive personalized medicine. The effective promotion of happiness at the individual and population level in order to guide policy requires a causal and mechanistic understanding of its modifiable determinants. With more than half of the world's population living in cities, it becomes, for example, important to understand how environmental, social, and lifestyle characteristics of urban life influence well-being. Yet, the correlation between many of these factors and the fact that they act in concert poses a large challenge in causal inference. The -omics biomarkers which form a pillar of personalized medicine are at the same time essential research instruments of modern-day observational epidemiology. The paper discusses how they can be applied to overcome the challenges researchers face in studies on the association of complex risk and protective patterns with specific well-being phenotypes and their relation to diseases. Important concepts are discussed in the context of well-being that were recently developed by epidemiologists to stimulate more investments into the understanding of the modifiable part of health (e.g., Exposome; Meet-in-the-Middle; Mendelian Randomization) to match the huge investments that went into genetic research.

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Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation

Abstract: This is the first demonstration of an association of preconception parental trauma with epigenetic alterations that is evident in both exposed parent and offspring, providing potential insight into how severe psychophysiological trauma can have intergenerational effects.

Cited by 569 publications

References 56 publications

Intergenerational Transmission of Stress in Humans

Intergenerational Transmission of Stress in Humans

Transgenerational effects of childhood conditions on third generation health and education outcomes

Happiness and its molecular fingerprints

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