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Distinct microRNA signature in human serum and germline after childhood trauma


Jawaid, Ali; Kunzi, Marina; Mansoor, Mahgul; Khan, Zain Yar; Abid, Anooshay; Taha, Muhammad; Rigotti, Serena; Thumfart, Kristina; Faisal, Saba; Chughtai, Omar; Mansuy, Isabelle M (2020). Distinct microRNA signature in human serum and germline after childhood trauma. medRxiv 20168393, Cold Spring Harbor Laboratory.

Abstract

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.

Abstract

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.

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Additional indexing

Item Type:Working Paper
Communities & Collections:04 Faculty of Medicine > Brain Research Institute
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:14 August 2020
Deposited On:02 Feb 2022 14:57
Last Modified:22 Sep 2023 12:29
Series Name:medRxiv
ISSN:0959-535X
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1101/2020.08.11.20168393
  • Content: Accepted Version
  • Language: English
  • Licence: Creative Commons: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)