Enduring effects of severe developmental adversity, including nutritional deprivation, on cortisol metabolism in aging Holocaust survivors.
Enduring effects of severe developmental adversity, including nutritional deprivation, on cortisol metabolism in aging Holocaust survivors.
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严重的发育逆境（包括营养剥夺）对老年大屠杀幸存者的皮质醇代谢产生持久影响。
DOI：
10.1016/j.jpsychires.2008.12.003
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发表时间：
2009
影响因子：
4.8
通讯作者：
Seckl,JonathanR
中科院分区：
文献类型：
--
作者：
Yehuda,Rachel;Bierer,LindaM;Andrew,Ruth;Schmeidler,James;Seckl,JonathanR
在动物模型中，生命早期暴露于主要的环境挑战，如营养不良和压力，导致持续的心脏代谢，神经内分泌和情感影响。虽然这种影响与发病机制有关，但“发育编程”的广泛发生表明它具有适应功能。糖皮质激素可能介导“编程”，已知其代谢受啮齿动物早期生活事件的影响。为了研究这些关系在人类中，皮质醇代谢和心脏代谢疾病的表现进行了检查，在大屠杀幸存者的年龄在曝光和情感功能障碍，特别是终身创伤后应激障碍（PTSD）。METHODS五十一大屠杀幸存者和22名对照组无轴I障碍收集24小时尿样，并进行了评估精神疾病和心脏代谢诊断。用气相色谱-质谱联用（GC-MS）分析皮质类固醇及其代谢产物，用放射免疫分析（RIA）测定皮质醇，用GC-MS分析5α-四氢皮质醇（5α-THF）和总糖皮质激素的含量。后者与5α-还原酶和11β-羟基类固醇脱氢酶（11β-HSD）2型的皮质醇代谢降低相关。最大的递减与大屠杀暴露的最早年龄和不太严重的PTSD相关。心脏代谢表现与11β-HSD-2活性降低相关。在对照组中，5α-还原酶与创伤相关症状呈正相关（即，与大屠杀无关的创伤暴露）。结论：发育过程中的极端营养不良和相关压力与糖皮质激素代谢特定途径的长期改变有关。这些影响可能是适应性的，并与晚年心脏代谢和压力相关疾病的风险降低有关。
OBJECTIVEIn 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).METHODSFifty-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).RESULTSHolocaust survivors showed reduced cortisol by RIA, and decreased levels of 5α-tetrahydrocortisol (5α-THF) and total glucocorticoid production by GC–MS. The latter was associated with lower cortisol metabolism by 5α-reductase and 11β-hydroxysteroid dehydrogenase (11β-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 11β-HSD-2 activity. In controls, 5α-reductase was positively associated with trauma-related symptoms (i.e., to traumatic exposures unrelated to the Holocaust).CONCLUSIONExtreme 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.