Abstract
Transcriptome-wide screens of peripheral blood during the onset and development of posttraumatic stress disorder (PTSD) indicate widespread immune dysregulation. However, little is known as to whether biological sex and the type of traumatic event influence shared or distinct biological pathways in PTSD. We performed a combined analysis of five independent PTSD blood transcriptome studies covering seven types of trauma in 229 PTSD and 311 comparison individuals to synthesize the extant data. Analyses by trauma type revealed a clear pattern of PTSD gene expression signatures distinguishing interpersonal (IP)-related traumas from combat-related traumas. Co-expression network analyses integrated all data and identified distinct gene expression perturbations across sex and modes of trauma in PTSD, including one wound-healing module downregulated in men exposed to combat traumas, one IL-12-mediated signaling module upregulated in men exposed to IP-related traumas, and two modules associated with lipid metabolism and mitogen-activated protein kinase activity upregulated in women exposed to IP-related traumas. Remarkably, a high degree of sharing of transcriptional dysregulation across sex and modes of trauma in PTSD was also observed converging on common signaling cascades, including cytokine, innate immune, and type I interferon pathways. Collectively, these findings provide a broad view of immune dysregulation in PTSD and demonstrate inflammatory pathways of molecular convergence and specificity, which may inform mechanisms and diagnostic biomarkers for the disorder.
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Acknowledgements
We gratefully acknowledge the individual volunteers and their families, as well as the Marine and Navy volunteers for their military service and for their participation in these studies. Additionally, we thank Segman and colleagues (2005), as well as others, who have placed their data in the public domain. We thank the Marine and Navy volunteers for their military service and for their participation in this study. We also thank Dr Anna Tocheva for further critical reading/assessment of our manuscript.
Author contributions
DST and SJG assembled all the data from independent sources. MSB designed the research question, analyzed the data, and wrote the manuscript with DST. All remaining authors contributed to the generation of the original data and provided critical reading/assessment of the current manuscript.
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Breen, M., Tylee, D., Maihofer, A. et al. PTSD Blood Transcriptome Mega-Analysis: Shared Inflammatory Pathways across Biological Sex and Modes of Trauma. Neuropsychopharmacol. 43, 469–481 (2018). https://doi.org/10.1038/npp.2017.220
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DOI: https://doi.org/10.1038/npp.2017.220
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