Abstract
AbstractChildhood 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.
Funder
Deutsche Forschungsgemeinschaft
Publisher
Springer Science and Business Media LLC
Subject
Biological Psychiatry,Cellular and Molecular Neuroscience,Psychiatry and Mental health
Reference85 articles.
1. Cecil, C. A. M., Viding, E., Fearon, P., Glaser, D. & McCrory, E. J. Disentangling the mental health impact of childhood abuse and neglect. Child Abus. Negl. 63, 106–119 (2017).
2. Danese A. et al. Adverse childhood experiences and adult risk factors for age-related disease. Arch. Pediatr. Adolesc. Med. 163, 1135–1143 (2009).
3. Hughes, K. et al. The effect of multiple adverse childhood experiences on health: a systematic review and meta-analysis. Lancet Public Health 2, e356–e366 (2017).
4. Kessler, R. C. et al. Childhood adversities and adult psychopathology in the WHO World Mental Health Surveys. Br. J. Psychiatry 197, 378–385 (2010).
5. Danese, A. & Baldwin, J. R. Hidden wounds? Inflammatory links between childhood trauma and psychopathology. Annu. Rev. Psychol. 68, 517–544 (2017).
Cited by
20 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献