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Children and adolescents exposed to maltreatment already exhibit epigenetic patterns suggestive of heightened low-grade inflammation

Published online by Cambridge University Press:  01 September 2022

H. Palma-Gudiel
Affiliation:
Centre for Biomedical Research Network on Mental Health (CIBERSAM), Instituto De Salut Carlos Iii, Madrid, Spain
L. Marques Feixa*
Affiliation:
Centre for Biomedical Research Network on Mental Health (CIBERSAM), Instituto De Salut Carlos Iii, Madrid, Spain University of Barcelona, Evolutionary Biology, Ecology And Environmental Sciences, Barcelona, Spain
S. Romero
Affiliation:
Centre for Biomedical Research Network on Mental Health (CIBERSAM), Instituto De Salut Carlos Iii, Madrid, Spain Hospital Clínic, Department Of Child And Adolescent Psychiatry And Psychology, Barcelona, Spain
M. Rapado-Castro
Affiliation:
Centre for Biomedical Research Network on Mental Health (CIBERSAM), Instituto De Salut Carlos Iii, Madrid, Spain Hospital General Universitario Gregorio Marañón, Department Of Child And Adolescent Psychiatry, Madrid, Spain
H. Blasco-Fontecilla
Affiliation:
Centre for Biomedical Research Network on Mental Health (CIBERSAM), Instituto De Salut Carlos Iii, Madrid, Spain Hospital Puerta de Hierro, Department Of Child And Adolescent Psychiatry, Majadahona, Spain
I. Zorrilla
Affiliation:
Centre for Biomedical Research Network on Mental Health (CIBERSAM), Instituto De Salut Carlos Iii, Madrid, Spain Hospital Santiago Apostol, Department Of Psychiatry, Vitoria-Gasteiz, Spain
M. Martín
Affiliation:
Hospital Benito Menni, Unitat De Crisis D’adolescents, Sant Boi, Spain
Á. Castro Quintas
Affiliation:
Centre for Biomedical Research Network on Mental Health (CIBERSAM), Instituto De Salut Carlos Iii, Madrid, Spain University of Barcelona, Evolutionary Biology, Ecology And Environmental Sciences, Barcelona, Spain
J.L. Monteserin-Garcia
Affiliation:
Centre for Biomedical Research Network on Mental Health (CIBERSAM), Instituto De Salut Carlos Iii, Madrid, Spain University of Barcelona, Evolutionary Biology, Ecology And Environmental Sciences, Barcelona, Spain
E. Font
Affiliation:
Centre for Biomedical Research Network on Mental Health (CIBERSAM), Instituto De Salut Carlos Iii, Madrid, Spain Hospital Clínic, Department Of Child And Adolescent Psychiatry And Psychology, Barcelona, Spain
M. Ramirez
Affiliation:
Centre for Biomedical Research Network on Mental Health (CIBERSAM), Instituto De Salut Carlos Iii, Madrid, Spain Galdakao Mental Health Services, Child And Adolescent Mental Health, Galdakao, Spain
D. Moreno
Affiliation:
Centre for Biomedical Research Network on Mental Health (CIBERSAM), Instituto De Salut Carlos Iii, Madrid, Spain Hospital General Universitario Gregorio Marañón, Department Of Child And Adolescent Psychiatry, Madrid, Spain
M. Marín-Vila
Affiliation:
Centre for Biomedical Research Network on Mental Health (CIBERSAM), Instituto De Salut Carlos Iii, Madrid, Spain Hospital Puerta de Hierro, Department Of Child And Adolescent Psychiatry, Majadahona, Spain
N. Moreno
Affiliation:
Centre for Biomedical Research Network on Mental Health (CIBERSAM), Instituto De Salut Carlos Iii, Madrid, Spain University of Barcelona, Evolutionary Biology, Ecology And Environmental Sciences, Barcelona, Spain
E. Binder
Affiliation:
Max-Planck Institute of Psychiatry, Translational Research In Psychiatry, Munich, Germany
L. Fañanas
Affiliation:
Centre for Biomedical Research Network on Mental Health (CIBERSAM), Instituto De Salut Carlos Iii, Madrid, Spain University of Barcelona, Evolutionary Biology, Ecology And Environmental Sciences, Barcelona, Spain
*
*Corresponding author.

Abstract

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Introduction

Childhood maltreatment (CM) is one of the best described environmental risk factors for developing any psychiatric disorder, while it also confers increased odds for obesity, cardiometabolic disorders and all-cause mortality. Inflammation has been suggested to mediate the widespread clinical effects of CM. Previously, Ligthart et al. (2016) identified a polyepigenetic signature of circulating CRP levels, a measure of chronic low-grade inflammation, that has been reliably associated with a wide array of complex disorders. The study of this biomarker could dilucidate the mechanistic relationship between CM and psychiatric outcomes.

Objectives

Thus, CRP-associated epigenetic modifications were explored regarding proximal exposure to CM.

Methods

Genomic DNA was extracted from peripheral blood mononuclear cells of 157 children and adolescents (7 to 17 years old). Exposure to CM was assessed following the TASSCV criteria. Genome-wide DNA methylation was assessed by means of the EPIC array. Fifty-two out of the 58 original CRP-associated CpG sites surpassed quality control and were included in the analysis. Age, sex, psychopathological status and cell type proportions were included as covariates.

Results

DNA methylation at 12 out of 52 CpG sites (23%) was significantly associated with exposure to CM (p < .05); 8 of these associations survived correction for multiple testing (q < .05).

Conclusions

This is the first study to date to explore the relationship between childhood maltreatment and an epigenetic signature of chronic low-grade inflammation. Our findings underscore the presence of immune dysregulation early after exposure to CM; further studies are needed to assess the long-term clinical implications of this signature in psychiatric patients.

Disclosure

No significant relationships.

Type
Abstract
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
© The Author(s), 2022. Published by Cambridge University Press on behalf of the European Psychiatric Association
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