The effects of childhood maltreatment on epigenetic regulation of stress-response associated genes: an intergenerational approach

• Type of Material: Article
• Authors: Laura Ramo-Fernandez, Ulm University; Christina Boeck, Ulm University; Alexandra M. Koenig, Ulm University; Katharina Schury, Ulm University; Elisabeth Binder, Emory University; Harald Guendel, Ulm University; Joerg M. Fegert, Ulm University; Alexander Karabatsiakis, Ulm University; Iris-Tatjana Kolassa, Ulm University
• Language: English
• Date: 2019-04-18
• Publisher: Nature Publishing Group
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2019.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41598-018-36689-2
• Title of Journal or Parent Work: Scientific Reports
• Volume: 9
• Issue: 1
• Start Page: 983
• End Page: 983
• Grant/Funding Information: This work was funded by a grant from the Federal Ministry of Education and Research of Germany (funding number: 01KR1304A).; AKo was supported by a scholarship of the Konrad Adenauer Foundation and CB was supported by a scholarship of the Carl Zeiss Foundation.
• Keywords: Maternal exposure; Mechanisms; Corticotropin-releasing hormone; Risk; Glucocorticoid-receptor; FKBP5 Polymorphisms; Cortisol; Science & Technology; Abuse; Trauma; Multidisciplinary Sciences; Science & Technology - Other Topics; DNA Methylation
• Research Categories: Psychology, Behavioral; Psychology, Psychobiology; Biology, Genetics; Health Sciences, Human Development

Abstract

While biological alterations associated with childhood maltreatment (CM) have been found in affected individuals, it remains unknown to what degree these alterations are biologically transmitted to the next generation. We investigated intergenerational effects of maternal CM on DNA methylation and gene expression in N = 113 mother-infant dyads shortly after parturition, additionally accounting for the role of the FKBP5 rs1360780 genotype. Using mass array spectrometry, we assessed the DNA methylation of selected stress-response-associated genes (FK506 binding protein 51 [FKBP5], glucocorticoid receptor [NR3C1], corticotropin-releasing hormone receptor 1 [CRHR1]) in isolated immune cells from maternal blood and neonatal umbilical cord blood. In mothers, CM was associated with decreased levels of DNA methylation of FKBP5 and CRHR1 and increased NR3C1 methylation, but not with changes in gene expression profiles. Rs1360780 moderated the FKBP5 epigenetic CM-associated regulation profiles in a gene × environment interaction. In newborns, we found no evidence for any intergenerational transmission of CM-related methylation profiles for any of the investigated epigenetic sites. These findings support the hypothesis of a long-lasting impact of CM on the biological epigenetic regulation of stress-response mediators and suggest for the first time that these specific epigenetic patterns might not be directly transmitted to the next generation.