Maternal PTSD associates with greater glucocorticoid sensitivity in offspring of Holocaust survivors
Open accessAbstract
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.
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Maternal PTSD was associated with lower urinary cortisol levels and greater GR sensitivity as measured by the lysozyme inhibition test and the dexamethasone suppression test.
“Specifically, maternal PTSD was associated with lower urinary cortisol levels as well as greater GR sensitivity as measured by the lysozyme inhibition test (an in vitro measure of that sensitivity in peripheral tissue) as well as the dexamethasone suppression test (DST).”
From Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms (2018) · cites this paper as [63]
An interaction of maternal and paternal PTSD on urinary cortisol and the DST demonstrated decreased glucocorticoid sensitivity in offspring with paternal, but not maternal, PTSD.
“An interaction of maternal and paternal PTSD on urinary cortisol and the DST demonstrated a decreased glucocorticoid sensitivity in offspring with paternal, but not maternal, PTSD.”
From Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms (2018) · cites this paper as [63]
Several measures of GR sensitivity were directionally different in offspring of mothers vs. fathers with PTSD.
“In another study, several measures of GR sensitivity were found to be directionally different in offspring of mothers vs. fathers with PTSD 63 .”
From Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms (2018) · cites this paper as [63]
Alterations of FKBP5 have been associated with both PTSD and intergenerational effects.
“alterations of which have been associated with both PTSD and intergenerational effects (27,28).”
From Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation (2016) · cites this paper as [27]
The Results report an association between maternal PTSD and offspring glucocorticoid sensitivity, and the Discussion considers possible intergenerational mechanisms. Neither section identifies FKBP5 or links alterations of it to PTSD or intergenerational effects (searched: FKBP5 and FK506-binding protein 5). (LLM, conf=0.72)
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- Authors
- Lehrner, A., Bierer, L. M., Passarelli, V., Pratchett, L. C., Flory, J. D., Bader, H. N., Harris, I. R., Bedi, A., Daskalakis, N. P., Makotkine, I., & Yehuda, R.
- Affiliations
- James J. Peters VA Medical Center (US)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Lehrner, Amy
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2014-02
- Volume
- 40
- Pages
- 213-220
- ISSN
- 0306-4530 (ISSN-L)
- PMC
- PMC3967845
- OpenAlex
- W2013520895
- Cited by
- 160
- References
- 54
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 9 · 2023: 11 · 2022: 7 · 2021: 11 · 2020: 40 · 2019: 11 · 2018: 13 · 2017: 12 · 2016: 11 · 2015: 14 · 2014: 9
- FWCI
- 5.16
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR000067)
- National Institute of Mental Health (RC1MH088101)
- National Center for Research Resources (M01RR000071)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Keywords
- maternal PTSD, Holocaust survivors, intergenerational trauma, glucocorticoid sensitivity, glucocorticoid receptor sensitivity, dexamethasone suppression test, urinary cortisol, epigenetic programming
- MeSH terms
- Adult, Aged, Anxiety Disorders, Depressive Disorder, Fathers, Female, Glucocorticoids, Humans, Hydrocortisone, Male, Middle Aged, Mothers, Pregnancy, Prenatal Exposure Delayed Effects, Stress Disorders, Post-Traumatic, Case-Control Studies, Child of Impaired Parents, Survivors, Holocaust, Young Adult
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