Elsevier

Psychoneuroendocrinology

Volume 40, February 2014, Pages 213-220
Psychoneuroendocrinology

Maternal PTSD associates with greater glucocorticoid sensitivity in offspring of Holocaust survivors

https://doi.org/10.1016/j.psyneuen.2013.11.019Get rights and content

Summary

Intergenerational effects of trauma have been observed clinically in a wide range of populations, and parental PTSD has been associated with an increased risk for psychopathology in offspring. In studies of Holocaust survivor offspring, parental PTSD, and particularly maternal PTSD, has been associated with increased risk for PTSD, low basal urinary cortisol excretion and enhanced cortisol suppression in response to dexamethasone. Such findings implicate maternally derived glucocorticoid programming in the intergenerational transmission of trauma-related consequences, potentially resulting from in utero influences or early life experiences. This study investigated the relative influence of Holocaust exposure and PTSD in mothers and fathers on glucocorticoid sensitivity in offspring. Eighty Holocaust offspring and 15 offspring of non-exposed Jewish parents completed evaluations and provided blood and urine samples. Glucocorticoid sensitivity was evaluated using the lysozyme suppression test (LST), an in vitro measure of glucocorticoid receptor sensitivity in a peripheral tissue, the dexamethasone suppression test (DST), and 24-h urinary cortisol excretion. Maternal PTSD was associated with greater glucocorticoid sensitivity in offspring across all three measures of glucocorticoid function. An interaction of maternal and paternal PTSD on the DST and 24-h urinary cortisol showed an effect of decreased glucocorticoid sensitivity in offspring with paternal, but not maternal, PTSD. Although indirect, these findings are consistent with the hypothesis that epigenetic programming may be involved in the intergenerational transmission of trauma-related effects on glucocorticoid regulation.

Section snippets

Participants

The study was approved by the Institutional Review Board of the Mount Sinai School of Medicine (MSSM), and all subjects provided written informed consent prior to participation. Participants were recruited through print and online advertisements in Jewish news outlets, second generation and other Jewish electronic mailing lists, advertisements at MSSM, and by word-of-mouth. Of the 120 participants recruited from 2010 through 2012, 94 were offspring of at least one Holocaust survivor and 26 were

Results

Sample characteristics and comparisons between the offspring and control groups are reported in Table 2. The groups were not significantly different in age, gender, BMI or education. The offspring group was more likely than the comparison group to have a current anxiety disorder diagnosis and to report symptoms of depression and anxiety on self report measures. Offspring were also more likely to report more child abuse and neglect on the Childhood Trauma Questionnaire. Offspring had higher 24-h

Discussion

The major finding in this study is the demonstration of greater glucocorticoid sensitivity as indicated by both the LST and the DST, and lower urinary cortisol excretion in offspring, in association with maternal PTSD. Previous studies have demonstrated lower plasma cortisol levels in offspring in association with maternal PTSD (Yehuda et al., 2007b). Additionally, higher cortisol suppression in response to DEX has been demonstrated in an independent cohort of Holocaust offspring in association

Role of funding source

This work was supported by 1RC1MH088101-01 “Identification of an Epigenetic Risk Marker for PTSD” and Grant Number #UL1TR000067 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH). The NIMH and NIH had no further role in the study design; in the collection, analysis and interpretation of the data; in the writing of the report; or in the decision to submit the paper for publication.

Conflict of interest statement

The authors have no conflict of interest to report.

Acknowledgements

We gratefully acknowledge Erin Koch for database management.

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      90% of the genes associated with mental health in children were also previously reported to be resistant to demethylation, highlighting them as candidates for transgenerational epigenetic inheritance. As same as for depression, studies have demonstrated that offspring of PTSD holocaust survivors presents higher risk for PTSD in adult life (Yehuda et al., 1998, 2001; Yehuda et al., 2008; Danieli et al., 2017) and this effect could be mediated by epigenetic inheritance mechanisms, such as decreased methylation and increased expression of FKBP5 (Yehuda et al., 2016; Bierer et al., 2020;), and decreased NR3C1 methylation (Yehuda et al., 2014) and increased glucocorticoid sensitivity (Yehuda et al., 2007a,b; Bader et al., 2014; Lehrner et al., 2014). Scharf (2007) also showed that grandchildren of holocaust survivor also present impaired psychological functioning, suggesting possible traces of trauma in the third generation.

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