title: Elevation of 11β-hydroxysteroid dehydrogenase type 2 activity in Holocaust survivor offspring: evidence for an intergenerational effect of maternal trauma exposure.
abstract: BACKGROUND
  Adult offspring of Holocaust survivors comprise an informative cohort in which to study intergenerational transmission of the effects of trauma exposure. Lower cortisol and enhanced glucocorticoid sensitivity have been previously demonstrated in Holocaust survivors with PTSD, and in offspring of Holocaust survivors in association with maternal PTSD. In other work, reduction in the activity of the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD-2), which inactivates cortisol, was identified in Holocaust survivors in comparison to age-matched, unexposed Jewish controls. Therefore, we investigated glucocorticoid metabolism in offspring of Holocaust survivors to evaluate if similar enzymatic decrements would be observed that might help to explain glucocorticoid alterations previously shown for Holocaust offspring.
  
  
  METHODS
  Holocaust offspring (n=85) and comparison subjects (n=27) were evaluated with clinical diagnostic interview and self-rating scales, and asked to collect a 24-h urine sample from which concentrations of cortisol and glucocorticoid metabolites were assayed by GCMS. 11β-HSD-2 activity was determined as the ratio of urinary cortisone to cortisol.
  
  
  RESULTS
  Significantly reduced cortisol excretion was observed in Holocaust offspring compared to controls (p=.046), as had been shown for Holocaust survivors. However, 11β-HSD-2 activity was elevated for offspring compared to controls (p=.008), particularly among those whose mothers had been children, rather than adolescents or adults, during World War II (p=.032). The effect of paternal Holocaust exposure could not be reliably investigated in the current sample.
  
  
  CONCLUSIONS
  The inverse association of offspring 11β-HSD-2 activity with maternal age at Holocaust exposure is consistent with the influence of glucocorticoid programming. Whereas a long standing reduction in 11β-HSD-2 activity among survivors is readily interpreted in the context of Holocaust related deprivation, understanding the directional effect on offspring will require replication and further exploration.
authors: James J. Peters VA Medical Center, Bronx, NY, United States; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
authors: Linda M
authors: LM
authors: Bierer
authors: James J. Peters VA Medical Center, Bronx, NY, United States; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
authors: Heather N
authors: HN
authors: Bader
authors: James J. Peters VA Medical Center, Bronx, NY, United States; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
authors: Nikolaos P
authors: NP
authors: Daskalakis
authors: James J. Peters VA Medical Center, Bronx, NY, United States; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
authors: Amy L
authors: AL
authors: Lehrner
authors: James J. Peters VA Medical Center, Bronx, NY, United States; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
authors: Iouri
authors: I
authors: Makotkine
authors: University of Edinburgh, Queen's Medical Research Institute, Edinburgh EH16 4TJ, UK.
authors: Jonathan R
authors: JR
authors: Seckl
authors: James J. Peters VA Medical Center, Bronx, NY, United States; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States. Electronic address: Rachel.yehuda@va.gov.
authors: Rachel
authors: R
authors: Yehuda
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D032721:Adult Children / Q000523:psychology; D002648:Child; D002675:Child, Preschool; D015988:Cohort Effect; D005260:Female; D017767:Holocaust / Q000523:psychology*; D006801:Humans; D007585:Jews / Q000523:psychology; D008297:Male; D008423:Maternal Age; D018811:Maternal Exposure / Q000009:adverse effects; D008875:Middle Aged; D018812:Paternal Exposure / Q000009:adverse effects; D011247:Pregnancy; D013313:Stress Disorders, Post-Traumatic / Q000201:enzymology / Q000378:metabolism; D017741:Survivors / Q000523:psychology*; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2
keywords: 11β-Hydroxysteriod dehydrogenase type 2; Biomarkers; Cortisol; Developmental programming; Glucocorticoid metabolism; HPA axis; Holocaust; Intergenerational; Offspring; PTSD