Enduring effects of severe developmental adversity, including nutritional deprivation, on cortisol metabolism in aging Holocaust survivors
Open accessAbstract
Objective In animal models, early life exposure to major environmental challenges such as malnutrition and stress results in persisting cardiometabolic, neuroendocrine and affective effects. While such effects have been associated with pathogenesis, the widespread occurrence of 'developmental programming' suggests it has adaptive function. Glucocorticoids may mediate 'programming' and their metabolism is known to be affected by early life events in rodents. To examine these relationships in humans, cortisol metabolism and cardiometabolic disease manifestations were examined in Holocaust survivors in relation to age at exposure and affective dysfunction, notably lifetime posttraumatic stress disorder (PTSD).Methods Fifty-one Holocaust survivors and 22 controls without Axis I disorder collected 24-h urine samples and were evaluated for psychiatric disorders and cardiometabolic diagnoses. Corticosteroids and their metabolites were assayed by gas chromatography-mass spectroscopy (GC-MS); cortisol was also measured by radioimmunoassay (RIA).Results Holocaust survivors showed reduced cortisol by RIA, and decreased levels of 5alpha-tetrahydrocortisol (5alpha-THF) and total glucocorticoid production by GC-MS. The latter was associated with lower cortisol metabolism by 5alpha-reductase and 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type-2. The greatest decrements were associated with earliest age of Holocaust exposure and less severe PTSD symptomatology. Cardiometabolic manifestations were associated with decreased 11beta-HSD-2 activity. In controls, 5alpha-reductase was positively associated with trauma-related symptoms (i.e., to traumatic exposures unrelated to the Holocaust).Conclusion Extreme malnutrition and related stress during development is associated with long-lived alterations in specific pathways of glucocorticoid metabolism. These effects may be adaptive and link with lower risks of cardiometabolic and stress-related disorders in later life.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Lower 11β-HSD-2 activity was observed in Holocaust survivors compared with control subjects, presumably reflecting an enduring adaptive response to extreme nutritional deprivation.
“For example, lower 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD-2) activity was observed in Holocaust survivors compared with control subjects, presumably reflecting an enduring adaptive response to extreme nutritional deprivation (19).”
From Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation (2016) · cites this paper as [19]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
1 retracted
Bremner, J. D., Vythilingam, M., Anderson, G., Vermetten, E. H. G. J. M., McGlashan, T. H., Heninger, G. R., Rasmusson, A. M., Southwick, S. M., & Charney, D. S. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(02)01912-1 · Cited by 111 · see citing works
RetractedThe development of a Clinician-Administered PTSD Scale
Blake, D. D., Weathers, F. W., Nagy, L. M., Kaloupek, D. G., Gusman, F. D., Charney, D. S., & Keane, T. M. (1995) · Journal of Traumatic Stress · doi:10.1002/jts.2490080106 · Cited by 5,024 · see citing works
Heim, C. (2000) · JAMA · doi:10.1001/jama.284.5.592 · Cited by 1,968 · see citing works
Living with the Past: Evolution, Development, and Patterns of Disease
Gluckman, P. D., & Hanson, M. A. (2004) · Science · doi:10.1126/science.1095292 · Cited by 1,917 · see citing works
Mineralocorticoid action: target tissue specificity is enzyme, not receptor, mediated
Funder, J. W., Pearce, P. T., Smith, R., & Smith, A. I. (1988) · Science · doi:10.1126/science.2845584 · Cited by 1,628 · see citing works
Glucose tolerance in adults after prenatal exposure to famine
Ravelli, A., van der Meulen, J., Michels, R., Osmond, C., Barker, D., Hales, C., & Bleker, O. (1998) · The Lancet · doi:10.1016/s0140-6736(97)07244-9 · Cited by 1,606 · see citing works
Post-Traumatic Stress Disorder
Yehuda, R. (2002) · New England Journal of Medicine · doi:10.1056/nejmra012941 · Cited by 1,134 · see citing works
Steroid 5α-reductase: two genes/two enzymes
Russell, D. W., & Wilson, J. D. (1994) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.63.070194.000325 · Cited by 1,105 · see citing works
Post-traumatic stress disorder in the community: an epidemiological study
Davidson, J. R. T., Hughes, D., Blazer, D. G., & George, L. K. (1991) · Psychological Medicine · doi:10.1017/s0033291700022352 · Cited by 969 · see citing works
Glucocorticoid exposure in utero: new model for adult hypertension
Benediktsson, R., Lindsay, R. S., Noble, J., Seckl, J. R., & Edwards, C. R. W. (1993) · The Lancet · doi:10.1016/0140-6736(93)90138-7 · Cited by 862 · see citing works
Heim, C., Newport, D. J., Bonsall, R., Miller, A. H., & Nemeroff, C. B. (2001) · American Journal of Psychiatry · doi:10.1176/appi.ajp.158.4.575 · Cited by 746 · see citing works
Schizophrenia After Prenatal Exposure to the Dutch Hunger Winter of 1944-1945
Susser, E. (1992) · Archives of General Psychiatry · doi:10.1001/archpsyc.1992.01820120071010 · Cited by 727 · see citing works
Seckl, J. R., & Walker, B. R. (2001) · Endocrinology · doi:10.1210/endo.142.4.8114 · Cited by 714 · see citing works
Yehuda, R., Engel, S. M., Brand, S. R., Seckl, J., Marcus, S. M., & Berkowitz, G. S. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-0550 · Cited by 711 · see citing works
Tissue-Specific Dysregulation of Cortisol Metabolism in Human Obesity
Rask, E., Olsson, T., Söderberg, S., Andrew, R., Livingstone, D. E. W., Johnson, O., & Walker, B. R. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.3.7453 · Cited by 657 · see citing works
SECKL, J. R., & MEANEY, M. J. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1314.006 · Cited by 556 · see citing works
Current status of cortisol findings in post-traumatic stress disorder
Yehuda, R. (2002) · Psychiatric Clinics of North America · doi:10.1016/s0193-953x(02)00002-3 · Cited by 511 · see citing works
Hypothalamic-pituitary-adrenal axis dysregulation in sexually abused girls
Bellis, M. D. D., Chrousos, G. P., Dorn, L. D., Burke, L. P., Helmers, K. F., Kling, M. A., Trickett, P. K., & Putnam, F. W. (1994) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.78.2.8106608 · Cited by 508 · see citing works
Structured Clinical Interview for DSM-IV (SCID)
Kübler, U. (2013) · Springer eBooks · doi:10.1007/978-1-4419-1005-9_66 · Cited by 445 · see citing works
Early onset of coronary artery disease after prenatal exposure to the Dutch famine
Painter, R. C., de Rooij, S. R., Bossuyt, P. M., Simmers, T. A., Osmond, C., Barker, D. J. P., Bleker, O. P., & Roseboom, T. J. (2006) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/84.1.322 · Cited by 392 · see citing works
Early onset of coronary artery disease after prenatal exposure to the Dutch famine
Painter, R. C., de Rooij, S. R., Bossuyt, P. M., Simmers, T. A., Osmond, C., Barker, D. J., Bleker, O. P., & Roseboom, T. J. (2006) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/84.2.322 · Cited by 392 · see citing works
Kaffman, A., & Meaney, M. J. (2007) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2007.01730.x · Cited by 385 · see citing works
Obesity and Gender Influence Cortisol Secretion and Metabolism in Man
Andrew, R., Phillips, D. I. W., & Walker, B. R. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.5.4951 · Cited by 351 · see citing works
Lindsay, R. S., Lindsay, R. M., Edwards, C. R. W., & Seckl, J. R. (1996) · Hypertension · doi:10.1161/01.hyp.27.6.1200 · Cited by 301 · see citing works
Antenatal corticosteroid therapy and blood pressure at 14 years of age in preterm children
Doyle, L. W., FORD, G. W., Davis, N., & Callanan, C. (2000) · Clinical Science · doi:10.1042/cs0980137 · Cited by 250 · see citing works
Glucocorticoid “Programming” and PTSD Risk
SECKL, J. R., & MEANEY, M. J. (2006) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1364.027 · Cited by 234 · see citing works
Cortisol and Catecholamines in Posttraumatic Stress Disorder
Young, E. A., & Breslau, N. (2004) · Archives of General Psychiatry · doi:10.1001/archpsyc.61.4.394 · Cited by 223 · see citing works
Yehuda, R., Golier, J. A., Yang, R.-K., & Tischler, L. (2004) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.02.010 · Cited by 196 · see citing works
Yau, J. L. W., Noble, J., Kenyon, C. J., Hibberd, C. J., Kotelevtsev, Y. V., Mullins, J. J., & Seckl, J. R. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.071562698 · Cited by 190 · see citing works
Circadian Rhythm of Salivary Cortisol in Holocaust Survivors With and Without PTSD
Yehuda, R., Golier, J. A., & Kaufman, S. (2005) · American Journal of Psychiatry · doi:10.1176/appi.ajp.162.5.998 · Cited by 177 · see citing works
Westerbacka, J., Yki‐Järvinen, H., Vehkavaara, S., Häkkinen, A., Andrew, R., Wake, D. J., Seckl, J. R., & Walker, B. R. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030596 · Cited by 176 · see citing works
Deficient inactivation of cortisol by 11β‐hydroxysteroid dehydrogenase in essential hypertension
Walker, B. R., Stewart, P. M., Shackleton, C. H. L., Padfield, P. L., & Edwards, C. R. W. (1993) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1993.tb01778.x · Cited by 174 · see citing works
Seckl, J. R. (2001) · Endocrinology · doi:10.1210/en.142.4.1371 · Cited by 172 · see citing works
Dannan, G. A., Guengerich, F. P., & Waxman, D. J. (1986) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)67446-0 · Cited by 167 · see citing works
Phillips, D. I. W. (2007) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2007.01801.x · Cited by 144 · see citing works
Gustafsson, J.-Α., & Stenbeŕg, Å. (1974) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)42988-8 · Cited by 142 · see citing works
Molecular Basis of Human Salt Sensitivity: The Role of the 11β-Hydroxysteroid Dehydrogenase Type 2*
Lovati, E., Ferrari, P., Dick, B., Jostarndt, K., Frey, B. M., Frey, F. J., Schorr, U., & Sharma, A. M. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.10.6098 · Cited by 142 · see citing works
Best, R., & Walker, B. R. (1997) · Clinical Endocrinology · doi:10.1046/j.1365-2265.1997.2471061.x · Cited by 126 · see citing works
Rasmuson, S., Andrew, R., Näsman, B., Seckl, J. R., Walker, B. R., & Olsson, T. (2001) · Biological Psychiatry · doi:10.1016/s0006-3223(00)01015-5 · Cited by 99 · see citing works
Longitudinal Assessment of Cognitive Performance in Holocaust Survivors with and without PTSD
Yehuda, R., Tischler, L., Golier, J. A., Grossman, R., Brand, S. R., Kaufman, S., & Harvey, P. D. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.03.069 · Cited by 86 · see citing works
Antenatal corticosteroid therapy and blood pressure at 14 years of age in preterm children
Doyle, L. W., Ford, G. W., Davis, N. M., et al. (2000) · Clinical Science · doi:10.1042/cs19990211 · Cited by 85 · see citing works
Influence of short-term dietary weight loss on cortisol secretion and metabolism in obese men
Johnstone, A. M., Faber, P., Andrew, R., Gibney, E. R., Elia, M., Lobley, G. E., Stubbs, R. J., & Walker, B. (2004) · European Journal of Endocrinology · doi:10.1530/eje.0.1500185 · Cited by 79 · see citing works
Obesity and Gender Influence Cortisol Secretion and Metabolism in Man
Andrew, R. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.83.5.1806 · Cited by 79 · see citing works
Self-citationGlucocorticoid metabolism and the Metabolic Syndrome: associations in an elderly cohort
Andrew, R., Galé, C. R., Walker, B. R., Seckl, J. R., & Martyn, C. N. (2002) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-2002-34591 · Cited by 78 · see citing works
Psychometric properties of the Civilian version of the Mississippi PTSD scale
Lauterbach, D., Vrana, S. R., King, D. W., & King, L. A. (1997) · Journal of Traumatic Stress · doi:10.1023/a:1024801607043 · Cited by 78 · see citing works
Ten‐year follow‐up study of cortisol levels in aging holocaust survivors with and without PTSD
Yehuda, R., Morris, A. T., Labinsky, E., Zemelman, S., & Schmeidler, J. (2007) · Journal of Traumatic Stress · doi:10.1002/jts.20228 · Cited by 65 · see citing works
Prevalence of Somatic and Psychiatric Disorders Among Former Prisoners of War
Eberly, R. E., & Engdahl, B. E. (1991) · Psychiatric Services · doi:10.1176/ps.42.8.807 · Cited by 63 · see citing works
Molecular Basis of Human Salt Sensitivity: The Role of the 11 -Hydroxysteroid Dehydrogenase Type 2
Lovati, E. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.84.10.3745 · Cited by 56 · see citing works
Paterson, J. M., Holmes, M. C., Kenyon, C. J., Carter, R., Mullins, J. J., & Seckl, J. R. (2006) · Endocrinology · doi:10.1210/en.2006-0603 · Cited by 46 · see citing works
van der Hal, E., van IJzendoorn, M. H., & Bakermans‐Kranenburg, M. J. (2007) · American Journal of Orthopsychiatry · doi:10.1037/0002-9432.77.4.514 · Cited by 35 · see citing works
Sense of coherence moderates late effects of early childhood Holocaust exposure
van der Hal, E., van IJzendoorn, M. H., & Bakermans‐Kranenburg, M. J. (2008) · Journal of Clinical Psychology · doi:10.1002/jclp.20528 · Cited by 30 · see citing works
Shimada, M., Murayama, N., Nagata, K., Hashimoto, H., Ishikawa, H., & Yamazoe, Y. (1997) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1996.9764 · Cited by 24 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
11β-hydroxysteroid dehydrogenases: Intracellular gate-keepers of tissue glucocorticoid action
Chapman, K., Holmes, M., & Seckl, J. (2013) · Physiological Reviews · doi:10.1152/physrev.00020.2012 · Cited by 887 · see citing works
Glucocorticoids, prenatal stress and the programming of disease
Harris, A., & Seckl, J. (2011) · Hormones and Behavior · doi:10.1016/j.yhbeh.2010.06.007 · Cited by 871 · see citing works
Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation
Yehuda, R., Daskalakis, N. P., Bierer, L. M., Bader, H. N., Klengel, T., Holsboer, F., & Binder, E. B. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.08.005 · Cited by 782 · see citing works
Intergenerational Transmission of Stress in Humans
Bowers, M. E., & Yehuda, R. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.247 · Cited by 564 · see citing works
Yehuda, R., Daskalakis, N. P., Desarnaud, F., Makotkine, I., Lehrner, A. L., Koch, E., Flory, J. D., Buxbaum, J. D., Meaney, M. J., & Bierer, L. M. (2013) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2013.00118 · Cited by 358 · see citing works
Yehuda, R., Flory, J. D., Bierer, L. M., Henn-Haase, C., Lehrner, A., Desarnaud, F., Makotkine, I., Daskalakis, N. P., Marmar, C. R., & Meaney, M. J. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.02.006 · Cited by 293 · see citing works
Minireview: Stress-related psychiatric disorders with low cortisol levels: A metabolic hypothesis
Yehuda, R., & Seckl, J. (2011) · Endocrinology · doi:10.1210/en.2011-1218 · Cited by 276 · see citing works
Glucocorticoids, developmental ‘programming’ and the risk of affective dysfunction
Seckl, J. R. (2007) · Progress in Brain Research · doi:10.1016/s0079-6123(07)67002-2 · Cited by 245 · see citing works
Self-citationEndocrine aspects of post-traumatic stress disorder and implications for diagnosis and treatment
Daskalakis, N. P., Lehrner, A., & Yehuda, R. (2013) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2013.05.004 · Cited by 209 · see citing works
Dashorst, P., Mooren, T. M., Kleber, R. J., de Jong, P. J., & Huntjens, R. J. C. (2019) · European Journal of Psychotraumatology · doi:10.1080/20008198.2019.1654065 · Cited by 207 · see citing works
Adulthood trauma and HPA-axis functioning in healthy subjects and PTSD patients: A meta-analysis
Klaassens, E. R., Giltay, E. J., Cuijpers, P. J., van Veen, T., & Zitman, F. G. (2011) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.07.003 · Cited by 179 · see citing works
Neural Regulation of the Stress Response: The Many Faces of Feedback
Myers, B., McKlveen, J. M., & Herman, J. P. (2012) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-012-9801-y · Cited by 175 · see citing works
“Despite GC hyposecretion, PTSD patients may actually have prolonged GC exposure following stress due to reduced activity of GC-metabolizing enzymes (Yehuda et al. 2009; Yehuda and Seckl 2011).”
Roberts, A. G., & Lopez‐Duran, N. L. (2018) · Comprehensive Psychiatry · doi:10.1016/j.comppsych.2018.10.008 · Cited by 131 · see citing works
Cultural trauma and epigenetic inheritance
Lehrner, A. L., & Yehuda, R. (2018) · Development and Psychopathology · doi:10.1017/s0954579418001153 · Cited by 128 · see citing works
Minireview: Transgenerational Inheritance of the Stress Response: A New Frontier in Stress Research
Matthews, S. G., & Phillips, D. I. W. (2009) · Endocrinology · doi:10.1210/en.2009-0916 · Cited by 118 · see citing works
Pineles, S., Nillni, Y., Pinna, G., Irvine, J., Webb, A., Hall, K. A. A., Hauger, R., Miller, M. W., Resick, P., Orr, S., et al. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.04.024 · Cited by 99 · see citing works
Hair cortisol concentrations in mental disorders: A systematic review
Koumantarou Malisiova, E., Mourikis, I., Darviri, C., Nicolaides, N. C., Zervas, I. M., Papageorgiou, C., & Chrousos, G. P. (2021) · Physiology & Behavior · doi:10.1016/j.physbeh.2020.113244 · Cited by 99 · see citing works
Transgenerational inheritance of stress pathology
Matthews, S. G., & Phillips, D. I. (2011) · Experimental Neurology · doi:10.1016/j.expneurol.2011.01.009 · Cited by 91 · see citing works
Chang, J. P., Su, K., Mondelli, V., & Pariante, C. M. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01550-0 · Cited by 91 · see citing works
Metabolomic analysis of male combat veterans with post traumatic stress disorder
Mellon, S. H., Bersani, F. S., Lindqvist, D., Hammamieh, R., Donohue, D., Dean, K., Jett, M., Yehuda, R., Flory, J., Reus, V. I., et al. (2019) · PLOS ONE · doi:10.1371/journal.pone.0213839 · Cited by 85 · see citing works
Programming the Brain and Behaviour by Early‐Life Stress: A Focus on Neuroactive Steroids
Brunton, P. J. (2015) · Journal of Neuroendocrinology · doi:10.1111/jne.12265 · Cited by 85 · see citing works
Intergenerational Effects of Maternal Holocaust Exposure on <i>FKBP5</i> Methylation
Bierer, L. M., Bader, H. N., Daskalakis, N. P., Lehrner, A., Provençal, N., Wiechmann, T., Klengel, T., Makotkine, I., Binder, E. B., & Yehuda, R. (2020) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2019.19060618 · Cited by 86 · see citing works
Self-citationPsychological Distress and Metabolomic Markers: A Systematic Review
Zhu, Y., Jha, S. C., Shutta, K. H., Huang, T., Balasubramanian, R., Clish, C. B., Hankinson, S. E., & Kubzansky, L. D. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104954 · Cited by 89 · see citing works
Matheson, K., Seymour, A. M., Landry, J., Ventura, K., Arsenault, E., & Anisman, H. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph19116455 · Cited by 88 · see citing works
Räikkönen, K., Lahti‐Pulkkinen, M., Heinonen, K., Pesonen, A., Wahlbeck, K., Kajantie, E., Osmond, C., Barker, D. J. P., & Eriksson, J. G. (2010) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2010.07.003 · Cited by 77 · see citing works
Rasmusson, A. M., King, M. W., Valovski, I. T., Gregor, K. L., Scioli, E. R., Pineles, S. L., Hamouda, M., Nillni, Y. I., Anderson, G. M., & Pinna, G. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.11.027 · Cited by 71 · see citing works
Early Adverse Care, Stress Neurobiology, and Prevention Science: Lessons Learned
Bruce, J., Gunnar, M. R., Pears, K. C., & Fisher, P. A. (2013) · Prevention Science · doi:10.1007/s11121-012-0354-6 · Cited by 70 · see citing works
Maternal Exposure to the Holocaust and Health Complaints in Offspring
Flory, J. D., Bierer, L. M., & Yehuda, R. (2011) · Disease Markers · doi:10.1155/2011/250470 · Cited by 67 · see citing works
Rasmusson, A. M., & Pineles, S. L. (2018) · Current Psychiatry Reports · doi:10.1007/s11920-018-0908-9 · Cited by 62 · see citing works
Bierer, L. M., Bader, H. N., Daskalakis, N. P., Lehrner, A. L., Makotkine, I., Seckl, J. R., & Yehuda, R. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.06.001 · Cited by 57 · see citing works
Sex-specific effects of prenatal stress on glucose homoeostasis and peripheral metabolism in rats.
Brunton, P., Sullivan, K., Kerrigan, D., Russell, J., Seckl, J., & Drake, A. (2013) · Journal of Endocrinology · doi:10.1530/joe-12-0540 · Cited by 59 · see citing works
Increased Systemic Cortisol Metabolism in Patients With Schizophrenia and Bipolar Disorder
Steen, N. E., Methlie, P., Lorentzen, S., Hope, S., Barrett, E. A., Larsson, S., Mork, E., Almås, B., Løvås, K., Agartz, I., et al. (2011) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.10m06068yel · Cited by 52 · see citing works
Zhang, Q., Chen, Z., Chen, S., Xu, Y., & Deng, H. (2016) · Steroids · doi:10.1016/j.steroids.2016.12.008 · Cited by 50 · see citing works
The public reception of putative epigenetic mechanisms in the transgenerational effects of trauma
Yehuda, R., Lehrner, A. L., & Bierer, L. M. (2018) · Current Zoology · doi:10.1093/eep/dvy018 · Cited by 51 · see citing works
Brunton, P. J., Donadio, M. V. F., Yao, S. T., Greenwood, M., Seckl, J. R., Murphy, D., & Russell, J. A. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.5104-13.2015 · Cited by 48 · see citing works
Ageing Holocaust survivors in Australia
Paratz, E. D., & Katz, B. (2011) · The Medical Journal of Australia · doi:10.5694/j.1326-5377.2011.tb03771.x · Cited by 42 · see citing works
Mbiydzenyuy, N. E., Hemmings, S. M. J., & Qulu, L. (2022) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2022.977416 · Cited by 40 · see citing works
Bader, H. N., Bierer, L. M., Lehrner, A., Makotkine, I., Daskalakis, N. P., & Yehuda, R. (2014) · Frontiers in Endocrinology · doi:10.3389/fendo.2014.00103 · Cited by 36 · see citing works
Self-citationGillespie, C. F., Almli, L. M., Smith, A. K., Bradley, B., Kerley, K. A., Crain, D. F., Mercer, K. B., Weiss, T., Phifer, J. E., Tang, Y., et al. (2013) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32147 · Cited by 34 · see citing works
The biological impacts of Indigenous residential school attendance on the next generation
Chief Moon-Riley, K., Copeland, J. L., Metz, G. A. S., & Currie, C. L. (2019) · SSM - Population Health · doi:10.1016/j.ssmph.2018.100343 · Cited by 34 · see citing works
Cortisol metabolism in critical illness
Boonen, E., & den Berghe, G. V. (2014) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000066 · Cited by 32 · see citing works
Iozzo, P., Holmes, M. C., Schmidt, M. V., Cirulli, F., Guzzardi, M. A., Berry, A., Balsevich, G., Andreassi, M. G., Wesselink, J., Liistro, T., et al. (2014) · Obesity Facts · doi:10.1159/000362656 · Cited by 30 · see citing works
Dmytriv, T. R., Tsiumpala, S. A., Semchyshyn, H. M., Storey, K. B., & Lushchak, V. I. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1222826 · Cited by 33 · see citing works
Genome‐wide DNA methylation investigation of glucocorticoid exposure within buccal samples
Braun, P., Tanaka‐Sahker, M., Chan, A. C., Jellison, S. S., Klisares, M. J., Hing, B. W. Q., Shabbir, Y., Gaul, L. N., Nagahama, Y., Robles, J., et al. (2019) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12835 · Cited by 29 · see citing works
Laham, B. J., Murthy, S. S., Hanani, M., Clappier, M., Boyer, S., Vasquez, B., & Gould, E. (2022) · Nature Communications · doi:10.1038/s41467-022-35068-w · Cited by 29 · see citing works
Lehrner, A. L., Hildebrandt, T., Bierer, L. M., Flory, J. D., Bader, H. N., Makotkine, I., & Yehuda, R. (2021) · Behaviour Research and Therapy · doi:10.1016/j.brat.2021.103924 · Cited by 28 · see citing works
A latent profile analysis of PTSD symptoms among UK treatment seeking veterans
Murphy, D., Ross, J., Busuttil, W., Greenberg, N., & Armour, C. (2019) · European Journal of Psychotraumatology · doi:10.1080/20008198.2018.1558706 · Cited by 26 · see citing works
Fraga, M. C., de Moura, E. G., Silva, J. O., Bonomo, I. T., Filgueiras, C. C., Abreu‐Villaça, Y., Passos, M. C. F., Lisboa, P. C., & Manhães, A. C. (2011) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2011.07.007 · Cited by 26 · see citing works
Rasmusson, A. M., Pineles, S. L., Brown, K. D., & Pinna, G. (2021) · Journal of Neuroendocrinology · doi:10.1111/jne.13062 · Cited by 24 · see citing works
SRD5A2 is associated with increased cortisol metabolism in schizophrenia spectrum disorders
Steen, N. E., Tesli, M., Kähler, A. K., Methlie, P., Hope, S., Barrett, E. A., Larsson, S., Mork, E., Løvås, K., Røssberg, J. I., et al. (2010) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2010.08.013 · Cited by 21 · see citing works
Posttraumatic Stress Disorder and Dementia in Holocaust Survivors
Sperling, W., Kreil, S. K., & Biermann, T. (2011) · The Journal of Nervous and Mental Disease · doi:10.1097/nmd.0b013e31820c71e0 · Cited by 21 · see citing works
Vin‐Raviv, N., Dekel, R., Barchana, M., Linn, S., & Keinan‐Boker, L. (2013) · International Psychogeriatrics · doi:10.1017/s1041610213002081 · Cited by 19 · see citing works
Stoye, D. Q., Andrew, R., Grobman, W. A., Adam, E. K., Wadhwa, P. D., Buß, C., Entringer, S., Miller, G. E., Boardman, J. P., Seckl, J. R., et al. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgz313 · Cited by 19 · see citing works
Vanaelst, B., Rivet, N., Huybrechts, I., Ludes, B., Henauw, S. D., & Raul, J. (2013) · Analytical Methods · doi:10.1039/c3ay26570f · Cited by 18 · see citing works
Endocrine Aspects of PTSD: Hypothalamic-Pituitary-Adrenal (HPA) Axis and Beyond
Daskalakis, N. P., McGill, M. A., Lehrner, A. L., & Yehuda, R. (2015) · Springer eBooks · doi:10.1007/978-3-319-08613-2_130-1 · Cited by 18 · see citing works
Glucocorticoid Regulation of Food-Choice Behavior in Humans: Evidence from Cushing's Syndrome
Moeller, S. J., Couto, L., Cohen, V. V., Lalazar, Y., Makotkine, I., Williams, N., Yehuda, R., Goldstein, R. Z., & Geer, E. B. (2016) · Frontiers in Neuroscience · doi:10.3389/fnins.2016.00021 · Cited by 16 · see citing works
Endocrine Aspects of PTSD: Hypothalamic-Pituitary-Adrenal (HPA) Axis and Beyond
Daskalakis, N. P., McGill, M. A., Lehrner, A. L., & Yehuda, R. (2016) · Springer eBooks · doi:10.1007/978-3-319-08359-9_130 · Cited by 16 · see citing works
Klinger-König, J., Frenzel, S., Hannemann, A., Wittfeld, K., Bülow, R., Friedrich, N., Nauck, M. A., Völzke, H., & Grabe, H. J. (2021) · Neurobiology of Stress · doi:10.1016/j.ynstr.2021.100416 · Cited by 14 · see citing works
Maternal Diet, Oocyte Nutrition and Metabolism, and Offspring Health
Velazquez, M. A., & Fleming, T. P. (2012) · Springer eBooks · doi:10.1007/978-0-85729-826-3_22 · Cited by 12 · see citing works
Gonçalves, R., Lages, A. C., Rodrigues, H., Pedrozo, A. L., Coutinho, E. S. F., Neylan, T., Figueira, I. L. D. V., & Ventura, P. R. (2011) · Archives of Clinical Psychiatry (São Paulo) · doi:10.1590/s0101-60832011000400008 · Cited by 12 · see citing works
Plag, J., Schumacher, S., Schmid, U., & Ströhle, A. (2013) · Neuropsychiatry · doi:10.2217/npy.13.6 · Cited by 12 · see citing works
Developmental and adult stress: effects of steroids and neurosteroids
Gore, I. R., & Gould, E. (2024) · Stress · doi:10.1080/10253890.2024.2317856 · Cited by 11 · see citing works
Aftermath of Genocide: Holocaust Survivors' Dissociation Moderates Offspring Level of Cortisol
van IJzendoorn, M. H., Fridman, A., Bakermans‐Kranenburg, M. J., & Sagi‐Schwartz, A. (2012) · Journal of Loss and Trauma · doi:10.1080/15325024.2012.679132 · Cited by 10 · see citing works
Bar-Sadeh, B., Amichai, O. E., Pnueli, L., Begum, K., Leeman, G., Emes, R. D., Stöger, R. J., Bentley, G. R., & Melamed, P. (2022) · BMC Biology · doi:10.1186/s12915-021-01219-6 · Cited by 9 · see citing works
Transgenerational risks by exposure in utero
Velazquez, M. A., & Fleming, T. P. (2013) · Cambridge University Press eBooks · doi:10.1017/cbo9781139135030.031 · Cited by 8 · see citing works
Vanaelst, B., Michels, N., Huybrechts, I., Clays, E., Flórez, M. R., Balcaen, L. I. L., Resano, M., Aramendía, M., Vanhaecke, F., Rivet, N., et al. (2013) · Biological Trace Element Research · doi:10.1007/s12011-013-9647-2 · Cited by 8 · see citing works
Stress and its effects across generations
Engmann, O., & Mansuy, I. M. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-813983-7.00018-5 · Cited by 7 · see citing works
Rasmusson, A. M., Novikov, O., Brown, K. D., Pinna, G., & Pineles, S. L. (2022) · Current Opinion in Endocrine and Metabolic Research · doi:10.1016/j.coemr.2022.100359 · Cited by 6 · see citing works
Somatic Diseases in Child Survivors of the Holocaust With Posttraumatic Stress Disorder
Sperling, W., Kreil, S., & Biermann, T. (2012) · The Journal of Nervous and Mental Disease · doi:10.1097/nmd.0b013e318253229e · Cited by 6 · see citing works
Sleep Disorders Among Holocaust Survivors
Lurie, I. (2017) · The Journal of Nervous and Mental Disease · doi:10.1097/nmd.0000000000000717 · Cited by 4 · see citing works
The meaning, challenges, and characteristics of art therapy for older Holocaust survivors
Israeli, R., Regev, D., & Goldner, L. (2021) · The Arts in Psychotherapy · doi:10.1016/j.aip.2021.101783 · Cited by 3 · see citing works
Epigenetics in Posttraumatic Stress Disorder
Hunter, R. G. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-417114-5.00016-4 · Cited by 3 · see citing works
Cultural Appropriation and Substance Use Disorder: A Case Report
Gallop, A., Chen, B. B., Gulati, V., & Barnes, A. A. (2020) · Journal of Child & Adolescent Substance Abuse · doi:10.1080/1067828x.2020.1805838 · Cited by 2 · see citing works
Sleep Disorders Among Holocaust Survivors
Lurie, I., & Levav, I. (2017) · Springer eBooks · doi:10.1007/978-1-4939-7148-0_33 · Cited by 2 · see citing works
Early Life Origins of Severe Personality Disorders: The Helsinki Birth Cohort Study
Lahti‐Pulkkinen, M. (2012) · Työväentutkimus Vuosikirja · Cited by 1 · see citing works
Glucocorticoids, Developmental “Programming,” and the Risk of Affective Dysfunction
Olabi, B., & Seckl, J. R. (2011) · Wiley eBooks · doi:10.1002/9783527633968.ch5 · Cited by 1 · see citing works
Early-life environment programs reproductive strategies through epigenetic regulation of SRD5A1Preprint
Bar-Sadeh, B., Eden, O., Pnueli, L., Begum, K., Leeman, G., Emes, R. D., Stöger, R. J., Bentley, G. R., & Melamed, P. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.09.16.299560 · Cited by 1 · see citing works
Contributos da Epigenética no âmbito da Medicina Legal
de SoutoSantos, R. T. (2013) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) · doi:10.34626/zz0h-qt21
Epigenetics - a cause for optimism?
Hanson, M. A. (2015) · Progress in Neurology and Psychiatry · doi:10.1002/pnp.377
Lebensqualität und psychische Belastung bei Vertriebenen des Zweiten Weltkrieges
Mathematisch-naturwissenschaftlichen Fakultät, I. (2013)
Gonçalves, R., Lages, A. C., Rodrigues, H., Pedrozo, A. L., da Silva, E. A., Coutinho, F., Neylan, T., Figueira, I. L. D. V., & Ventura, P. R. (2011)
Neuroendocrine Aspects of Posttraumatic Stress Disorder
Bader, H. N., & Yehuda, R. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-803592-4.00080-8
Developmental ORIgins of Healthy and Unhealthy AgeiNg
Iozzo, P., Holmes, M. C., Schmidt, M. V., Cirulli, F., Guzzardi, M. A., Berry, A., Balsevich, G., Andreassi, M. G., Wesselink, J., Liistro, T., et al. (2016)
Epigenetics in posttraumatic stress disorder
Richter, T. A., & Hunter, R. G. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-823577-5.00035-0 · Cited by 1 · see citing works
Straub, R. H. (2022) · Springer eBooks · doi:10.1007/978-3-662-65238-1_4
Chronic Immune System Activation
Straub, R. H. (2023) · Springer eBooks · doi:10.1007/978-3-662-66751-4_4
Bowe, C., Thomas, C. J., & Mackey, P. (2025) · Child and Adolescent Social Work Journal · doi:10.1007/s10560-025-01027-9
Ouss, L. (2012) · doi:10.3917/lps.mouch.2012.01.0212
Oxytocin as regulator of stress and inflammation in aging
Wright, K. D., Horta, M., Hayes, A., & Ebner, N. C. (2026) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2026.106924
- Authors
- Yehuda, R., Bierer, L. M., Andrew, R., Schmeidler, J., & Seckl, J. R.
- Affiliations
- James J. Peters VA Medical Center (US)
- The Queen's Medical Research Institute (GB)
- Corresponding author
- Yehuda, Rachel
- Venue
- Journal of Psychiatric Research
- Publisher
- Elsevier BV
- Published
- 2009-06
- Volume
- 43
- Issue
- 9
- Pages
- 877-883
- ISSN
- 0022-3956 (ISSN-L)
- PMC
- PMC2749458
- OpenAlex
- W2164552675
- Cited by
- 90
- References
- 51
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 7 · 2021: 6 · 2020: 5 · 2019: 5 · 2018: 7 · 2017: 2 · 2016: 5 · 2015: 7 · 2014: 6 · 2013: 13 · 2012: 6
- FWCI
- 2.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Psychiatric Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- Wellcome Trust
- National Institute of Mental Health (R01MH064675)
- National Center for Research Resources (M01RR000071)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Keywords
- Holocaust survivors, developmental adversity, early-life malnutrition, cortisol metabolism, glucocorticoid metabolism, post-traumatic stress disorder, 11β-hydroxysteroid dehydrogenase type 2, 5α-reductase, aging, cardiometabolic disease, age at exposure
- MeSH terms
- Adrenal Cortex Hormones, Aged, Aged, 80 and over, Aging, Chromatography, Gas, Female, Glucocorticoids, Humans, Hydrocortisone, Jews, Life Change Events, Male, Middle Aged, Radioimmunoassay, Mass Spectrometry, Stress Disorders, Post-Traumatic, Stress, Psychological, Tetrahydrocortisol, Case-Control Studies, Survivors, Holocaust, 11-beta-Hydroxysteroid Dehydrogenases, Cholestenone 5 alpha-Reductase, Malnutrition
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
