Distinct microRNA signature in human serum and germline after childhood trauma

Traumatic experiences during childhood can persistently alter mental and physical health in humans and have been implicated in transmission of symptoms to the progeny in animal models. Molecular evidence from these models implicates epigenetic/non-genetic factors, such as microRNAs (miRNAs), in the expression of trauma-induced symptoms and their transmission to the offspring. To confirm these findings in humans, we assembled three cohorts of subjects exposed to childhood trauma and examined selected miRNAs linked to psychological and pathophysiological manifestations of childhood trauma. Children aged 7-12 years (n = 72, control n = 30) exposed to paternal loss and maternal separation (PLMS) exhibited increase in two miRNAs, miR-16 and miR-375 in serum and reduced level of high-density lipoproteins (HDL) compared to control children. Comparable miRNA changes were observed in serum of adult men aged 18-25 years (n = 13, control n = 17) who had been exposed to PLMS at a young age. Finally, the same miRNAs were altered in sperm of adult men aged 21-50 years (n = 23, control n = 35) exposed to two or more significant traumatic events in childhood, assessed retrospectively using the standardized childhood trauma questionnaire (CTQ). In vitro experiments show that regulation of these miRNA involves the HDL receptor SRB-1, suggesting a link between trauma-associated miRNAs and metabolic alterations. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the University of Zurich, the Swiss Federal Institute of Technology, ETH-10 15-2 and ETH-17 13-2 and the Swiss National Science Foundation (NF 31003A_135715). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The research design and study procedures were reviewed and approved by two over-sight bodies: 1. National directorate of the SOS Children's Villages, Lahore, Pakistan 2. Executive board of the Chughtai Laboratories, Lahore, Pakistan (Authorization forms from both over-sight bodies have been added to the manuscript) All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All raw data is available upon request