Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany; Department of Clinical Psychology and Psychotherapy, University of Koblenz-Landau, Landau, Germany.
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany.
Psychoneuroendocrinology. 2019 May;103:219-224. doi: 10.1016/j.psyneuen.2019.01.017. Epub 2019 Jan 18.
Prenatal stress (PS) has been related to altered hypothalamic-pituitary-adrenal (HPA) axis activity later in life. So far, studies in children assessing HPA axis functioning have focused on salivary cortisol, reflecting daytime activity. The present work is part of a prospective study and aims to extend knowledge about the association between PS and HPA axis regulation in children. To do so, we investigated cortisol, cortisone, and the ratio cortisone/(cortisone + cortisol) in the first morning urine of 45-month-old children in relation to several measures of maternal stress during pregnancy. Urinary cortisol and cortisone were measured by online turbulent flow chromatography coupled with high performance liquid chromatography-tandem mass spectrometry. PS was defined as: perceived stress for aim 1 (Perceived Stress Scale; n = 280); presence of self-reported (n = 371) and expert-rated psychopathology for aim 2 (Mini International Neuropsychiatric Interview; n = 281); continuous measures of anxiety and depression for exploratory aim 3 (State-Trait Anxiety Inventory and Edinburgh Postnatal Depression Scale; n = 280). Aim 1: Perceived maternal PS showed negative associations with cortisol and cortisone levels. Aim 2: The presence of expert-rated maternal psychopathology was associated with reduced morning cortisone. Aim 3: Continuous measures of anxiety and depression showed negative associations with cortisol and cortisone levels. After correcting for multiple testing, perceived maternal PS (aim 1) and prenatal level of anxiety (aim 3) were significant predictors of children's urinary cortisol and cortisone in the morning (and, in the case of cortisone, also prenatal level of depression). The ratio cortisone/(cortisone + cortisol) as a global marker for the balance between the enzymes metabolizing cortisol to cortisone and vice versa (11β-hydroxysteroid dehydrogenases type 1 and 2; 11β-HSD1 and 2) was not associated with any measure of maternal PS (aims 1-3). The present study provides insight into possible programming effects of PS on nocturnal HPA axis activity and a proxy of 11β-HSD in a large sample. The results suggest that the nocturnal rate of cortisol production is lower in children exposed to PS, but do not support the hypothesis of divergent 11β-HSD activity.
产前应激（PS）与生命后期下丘脑-垂体-肾上腺（HPA）轴活性改变有关。迄今为止，评估儿童 HPA 轴功能的研究主要集中在唾液皮质醇上，反映了日间活动。本工作是一项前瞻性研究的一部分，旨在扩展关于 PS 与儿童 HPA 轴调节之间关联的知识。为此，我们研究了 45 个月大儿童晨尿中的皮质醇、皮质酮和皮质酮/（皮质酮+皮质醇）比值与怀孕期间母亲应激的几个测量值之间的关系。尿液中的皮质醇和皮质酮通过在线紊流色谱法与高效液相色谱-串联质谱法相结合进行测量。PS 定义为：目标 1 的感知压力（感知压力量表；n=280）；存在自我报告（n=371）和专家评定的精神病理学（迷你国际神经精神访谈；n=281）；探索性目标 3 的焦虑和抑郁的连续测量（状态-特质焦虑量表和爱丁堡产后抑郁量表；n=280）。目标 1：感知到的母亲 PS 与皮质醇和皮质酮水平呈负相关。目标 2：专家评定的母亲精神病理学与早晨皮质酮减少有关。目标 3：焦虑和抑郁的连续测量与皮质醇和皮质酮水平呈负相关。经过多次测试校正后，感知到的母亲 PS（目标 1）和产前焦虑水平（目标 3）是儿童晨尿中皮质醇和皮质酮的显著预测因子（皮质酮也是产前抑郁水平的预测因子）。皮质酮/（皮质酮+皮质醇）作为反映代谢皮质醇为皮质酮和反之亦然的酶（11β-羟类固醇脱氢酶 1 型和 2 型；11β-HSD1 和 2）平衡的全局标志物，与任何母亲 PS 测量值（目标 1-3）无关。本研究提供了关于 PS 对夜间 HPA 轴活动和 11β-HSD 大样本中替代物的编程影响的见解。结果表明，暴露于 PS 的儿童的夜间皮质醇生成率较低，但不支持 11β-HSD 活性不同的假说。
