Elevation of 11β-hydroxysteroid dehydrogenase type 2 activity in Holocaust survivor offspring: Evidence for an intergenerational effect of maternal trauma exposure
Elevation of 11β-hydroxysteroid dehydrogenase type 2 activity in Holocaust survivor offspring: Evidence for an intergenerational effect of maternal trauma exposure
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DOI：
10.1016/j.psyneuen.2014.06.001
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发表时间：
2014-10-01
影响因子：
3.7
通讯作者：
Yehuda, Rachel
中科院分区：
文献类型：
--
作者：
Bierer, Linda M.;Bader, Heather N.;Yehuda, Rachel
背景资料：大屠杀幸存者的成年后代组成了一个信息队列，在其中研究创伤暴露影响的代际传递。先前已在患有PTSD的大屠杀幸存者和与母亲PTSD相关的大屠杀幸存者的后代中证实了较低的皮质醇和增强的糖皮质激素敏感性。在另一项研究中，与年龄匹配的未暴露的犹太对照组相比，大屠杀幸存者中的11 β-羟类固醇脱氢酶2型（11 β-HSD-2）的活性降低，这种酶使皮质醇失活。因此，我们调查了大屠杀幸存者后代的糖皮质激素代谢，以评估是否会观察到类似的酶减量，这可能有助于解释先前显示的大屠杀后代的糖皮质激素改变。采用临床诊断访谈和自评量表对大屠杀后代（n = 85）和对照受试者（n = 27）进行评估，并要求收集24小时尿样，通过GCMS测定其中皮质醇和糖皮质激素代谢物的浓度。11 β-HSD-2的活性被确定为尿皮质醇的比率cortisol.Results：显着减少皮质醇的排泄量被观察到在大屠杀的后代相比，对照组（p = 0.046），已被证明为大屠杀幸存者。然而，与对照组相比，后代的11 β-HSD-2活性升高（p = 0.008），特别是在第二次世界大战期间，母亲是儿童而不是青少年或成年人的那些人中（p = 0.032）。父亲的大屠杀暴露的影响不能可靠地调查在当前sample.Conclusions：后代11 β-HSD-2活性与母亲的年龄在大屠杀暴露的负相关性是一致的糖皮质激素编程的影响。虽然幸存者中11 β-HSD-2活性的持续降低很容易解释，但在大屠杀相关剥夺的背景下，理解对后代的定向影响将需要复制和进一步探索。爱思唯尔有限公司出版
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 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-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. 11 beta-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, 11 beta-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 11 beta-HSD-2 activity with maternal age at Holocaust exposure is consistent with the influence of glucocorticoid programming. Whereas a tong standing reduction in 11 beta-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. Published by Elsevier Ltd.