Gene expression in cord blood links genetic risk for neurodevelopmental disorders with maternal psychological distress and adverse childhood outcomes.
Gene expression in cord blood links genetic risk for neurodevelopmental disorders with maternal psychological distress and adverse childhood outcomes.
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DOI：
10.1016/j.bbi.2018.05.016
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发表时间：
2018-10
期刊：
影响因子：
--
通讯作者：
Stein DJ
中科院分区：
文献类型：
--
作者：
Breen MS;Wingo AP;Koen N;Donald KA;Nicol M;Zar HJ;Ressler KJ;Buxbaum JD;Stein DJ
产前暴露于母亲的压力和抑郁已被确定为儿童早期不良行为和神经发育结果的危险因素。然而，母体精神病理学塑造后代发育的分子机制仍然知之甚少。我们对来自创伤后应激障碍(n = 20)、抑郁症(n = 31)和创伤后应激障碍合并抑郁(n = 13)母亲的新生儿脐带血样本进行了转录全组筛查，并与仔细匹配的创伤暴露对照组(n = 23)和健康母亲(n = 62)进行了比较。对母亲诊断的分析揭示了明确的基因表达特征模式，将有精神病史的母亲所生的新生儿与没有病史的母亲所生的新生儿区分开来。共表达网络分析发现，在母体诊断中存在明显的基因表达扰动，包括与轴突引导和mRNA稳定性有关的两个抑郁相关模块，以及与肿瘤坏死因子信号转导和细胞应激反应有关的两个PTSD相关模块。值得注意的是，这些与疾病相关的模块丰富了大脑表达的基因和自闭症谱系障碍和精神分裂症的遗传风险基因，这可能意味着发育结果受损的因果作用。这些分子变化先于24个月后临床测量的变化，包括受影响婴儿认知和社会情绪结果的降低。总而言之，这些发现表明，产前暴露在母亲的心理痛苦中会导致受影响后代的神经元、免疫学和行为异常，并支持寻找宫内环境中暴露于不利环境的早期生物标记物，并对有发育障碍风险的儿童进行分类。
Prenatal exposure to maternal stress and depression has been identified as a risk factor for adverse behavioral and neurodevelopmental outcomes in early childhood. However, the molecular mechanisms through which maternal psychopathology shapes offspring development remain poorly understood. We applied transcriptome-wide screens to 149 umbilical cord blood samples from neonates born to mothers with posttraumatic stress disorder (PTSD; n = 20), depression (n = 31) and PTSD with comorbid depression (n = 13), compared to carefully matched trauma exposed controls (n = 23) and healthy mothers (n = 62). Analyses by maternal diagnoses revealed a clear pattern of gene expression signatures distinguishing neonates born to mothers with a history of psychopathology from those without. Co-expression network analysis identified distinct gene expression perturbations across maternal diagnoses, including two depression-related modules implicated in axon-guidance and mRNA stability, as well as two PTSD-related modules implicated in TNF signaling and cellular response to stress. Notably, these disease-related modules were enriched with brain-expressed genes and genetic risk loci for autism spectrum disorder and schizophrenia, which may imply a causal role for impaired developmental outcomes. These molecular alterations preceded changes in clinical measures at twenty-four months, including reductions in cognitive and socio-emotional outcomes in affected infants. Collectively, these findings indicate that prenatal exposure to maternal psychological distress induces neuronal, immunological and behavioral abnormalities in affected offspring and support the search for early biomarkers of exposures to adverse in utero environments and the classification of children at risk for impaired development.
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影响因子：
--
作者：
Grote, Nancy K.;Bridge, Jeffrey A.;Gavin, Amelia R.;Melville, Jennifer L.;Iyengar, Satish;Katon, Wayne J.
通讯作者：
Katon, Wayne J.
影响因子：
2.2
作者：
DiPietro, Janet A.
通讯作者：
DiPietro, Janet A.
影响因子：
7.6
作者：
Breen, Michael S.;Tylee, Daniel S.;Glatt, Stephen J.
通讯作者：
Glatt, Stephen J.
影响因子：
3
作者：
Hoffman GE;Schadt EE
通讯作者：
Schadt EE
DOI：
10.1126/science.aag3194
发表时间：
2016-08-19
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Estes ML;McAllister AK
通讯作者：
McAllister AK