产前重度抑郁症、胎盘糖皮质激素和血清素信号传导以及婴儿皮质醇反应。
Prenatal Major Depressive Disorder, Placenta Glucocorticoid and Serotonergic Signaling, and Infant Cortisol Response.
作者信息
Stroud Laura R, Papandonatos George D, Parade Stephanie H, Salisbury Amy L, Phipps Maureen G, Lester Barry M, Padbury James F, Marsit Carmen J
机构信息
From the Department of Psychiatry and Human Behavior (Stroud, Parade, Salisbury, Lester), Warren Alpert Medical School, Brown University; Providence, Rhode Island; Centers for Behavioral and Preventive Medicine (Stroud), The Miriam Hospital, Providence, Rhode Island; Department of Biostatistics, School of Public Health (Papandonatos), Brown University, Providence, Rhode Island; Bradley/Hasbro Children's Research Center (Parade), Providence, Rhode Island; Department of Pediatrics (Salisbury, Lester, Padbury), Warren Alpert Medical School, Brown University, Providence, Rhode Island; Women & Infants' Hospital of Rhode Island (Salisbury, Phipps, Lester, Padbury), Providence, Rhode Island; Department of Obstetrics and Gynecology (Phipps), Warren Alpert Medical School, Brown University, Providence, Rhode Island; and Department of Environmental Health (Marsit), Rollins School of Public Health, Emory University, Atlanta, Georgia.
出版信息
Psychosom Med. 2016 Nov/Dec;78(9):979-990. doi: 10.1097/PSY.0000000000000410.
OBJECTIVES
Extending prior studies of prenatal adversity and depressive symptoms, we tested associations between maternal prenatal major depressive disorder (MDD) and infant cortisol regulation. Based on prior findings by our group, we also tested placenta glucocorticoid (HSD11B2 methylation) and serotonin (SLC6A4 gene expression) signaling as moderators of links between prenatal MDD and infant cortisol.
METHODS
Participants were 153 mother-infant pairs from a low-income, diverse sample (M [SD] age = 26 [6] years). Repeated structured diagnostic interviews were used to identify mothers with (a) prenatal MDD, (b) preconception-only MDD, and (c) controls. Placenta samples were assayed for HSD11B2 methylation and SLC6A4 gene expression. Infant salivary cortisol response to a neurobehavioral examination was assessed at 1 month.
RESULTS
Daughters of prenatal MDD mothers had 51% higher baseline (ratio = 1.51; 95% confidence interval [CI] = 1.01-2.27; p = .045) and 64% higher stress responsive cortisol (ratio = 1.64; 95% CI = 1.05-2.56; p = .03) than daughters of controls and 75% higher stress-responsive cortisol (ratio = 1.75; 95% CI = 1.04-2.94; p = .04) than daughters of preconception-only MDD mothers. HSD11B2 methylation moderated links between prenatal MDD and baseline cortisol (p = .02), with 1% methylation decreases associated with 9% increased baseline cortisol in infants of prenatal MDD mothers (ratio = 1.09; 95% CI = 1.01-1.16). SLC6A4 expression moderated links between prenatal MDD and cortisol response among boys alone (p = .007), with 10-fold increases in expression associated with threefold increases in stress-responsive cortisol (ratio = 2.87; 95% CI = 1.39-5.93) in sons of control mothers.
CONCLUSIONS
Results highlight specificity of associations between prenatal versus preconception MDD and cortisol regulation and the importance and complexity of placenta glucocorticoid and serotonergic pathways underlying the intergenerational transmission of risk from maternal adversity.
目的
在先前关于产前逆境与抑郁症状研究的基础上，我们测试了母亲产前重度抑郁症（MDD）与婴儿皮质醇调节之间的关联。基于我们小组先前的研究结果，我们还测试了胎盘糖皮质激素（HSD11B2甲基化）和血清素（SLC6A4基因表达）信号作为产前MDD与婴儿皮质醇之间联系的调节因素。
方法
参与者为153对母婴，来自低收入、多样化样本（平均年龄[标准差]=26[6]岁）。通过重复的结构化诊断访谈来识别患有（a）产前MDD、（b）仅孕前MDD和（c）对照组的母亲。对胎盘样本进行HSD11B2甲基化和SLC6A4基因表达检测。在婴儿1个月大时评估其唾液皮质醇对神经行为检查的反应。
结果
产前MDD母亲的女儿的基线皮质醇水平比对照组母亲的女儿高51%（比值=1.51；95%置信区间[CI]=1.01 - 2.27；p = 0.045），应激反应性皮质醇水平高64%（比值=1.64；95%CI = 1.05 - 2.56；p = 0.03），比仅孕前MDD母亲的女儿的应激反应性皮质醇水平高75%（比值=1.75；95%CI = 1.04 - 2.94；p = 0.04）。HSD11B2甲基化调节了产前MDD与基线皮质醇之间的联系（p = 0.02），在产前MDD母亲的婴儿中，甲基化每降低1%，基线皮质醇水平就会升高9%（比值=1.09；95%CI = 1.01 - 1.16）。SLC6A4表达仅在男孩中调节了产前MDD与皮质醇反应之间的联系（p = 0.007），在对照组母亲的儿子中，表达增加10倍与应激反应性皮质醇增加两倍相关（比值=2.87；95%CI = 1.39 - 5.93）。
结论
结果突出了产前与孕前MDD与皮质醇调节之间关联的特异性，以及胎盘糖皮质激素和血清素能途径在母亲逆境风险代际传递中的重要性和复杂性。
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