Department of Genetic Psychology, Faculty of Psychology, Ruhr University Bochum, Bochum, Germany.
Division of Hematology/Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Transl Psychiatry. 2020 Jan 27;10(1):34. doi: 10.1038/s41398-020-0730-0.
Childhood adversity is related to an increased risk for psychopathology in adulthood. Altered regulation of stress response systems, as well as the changes in stress-immune interplay have been suggested as potential mechanisms underlying these long-term effects. We have previously shown altered transcriptional responses to acute psychosocial stress in adults reporting the experience of childhood adversity. Here, we extend these analyses using a network approach. We performed a co-expression network analysis of genome-wide mRNA data derived from isolated monocytes, sampled 3 h after stress exposure from healthy adults, who experienced childhood adversity and a matched control group without adverse childhood experiences. Thirteen co-expression modules were identified, of which four modules were enriched for genes related to immune system function. Gene set enrichment analysis showed differential module activity between the early adversity and control group. In line with previous findings reporting a pro-inflammatory bias following childhood adversity, one module included genes associated with pro-inflammatory function (hub genes: IL6, TM4SF1, ADAMTS4, CYR61, CCDC3), more strongly expressed in the early adversity group. Another module downregulated in the early adversity group was related to platelet activation and wound healing (hub genes: GP9, CMTM5, TUBB1, GNG11, PF4), and resembled a co-expression module previously found over-expressed in post-traumatic stress disorder resilient soldiers. These discovery analysis results provide a system wide and more holistic understanding of gene expression programs associated with childhood adversity. Furthermore, identified hub genes can be used in directed hypothesis testing in future studies.
童年逆境与成年后精神病理学风险增加有关。应激反应系统调节异常，以及应激-免疫相互作用的变化，被认为是这些长期影响的潜在机制。我们之前已经表明，经历过童年逆境的成年人在急性心理社会应激后，其转录反应发生了改变。在这里，我们使用网络方法扩展了这些分析。我们对经历过童年逆境和无不良童年经历的对照组的健康成年人在应激暴露后 3 小时采集的分离单核细胞的全基因组 mRNA 数据进行了共表达网络分析。确定了 13 个共表达模块，其中 4 个模块富含与免疫系统功能相关的基因。基因集富集分析显示，早期逆境组和对照组之间的模块活性存在差异。与之前报告的童年逆境后促炎偏向一致，一个模块包含与促炎功能相关的基因（枢纽基因：IL6、TM4SF1、ADAMTS4、CYR61、CCDC3），在早期逆境组中表达更强。另一个在早期逆境组下调的模块与血小板激活和伤口愈合有关（枢纽基因：GP9、CMTM5、TUBB1、GNG11、PF4），并且与以前在创伤后应激障碍恢复力强的士兵中发现的过表达共表达模块相似。这些发现分析结果提供了与童年逆境相关的基因表达程序的系统全面和更全面的理解。此外，鉴定出的枢纽基因可以在未来的研究中用于有针对性的假设检验。
