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. 2022 Nov 10:13:945343.
doi: 10.3389/fpsyt.2022.945343. eCollection 2022.

A history of childhood maltreatment is associated with altered DNA methylation levels of DNA methyltransferase 1 in maternal but not neonatal mononuclear immune cells

Rezan Nehir Mavioglu  1 , Laura Ramo-Fernandez  1 , Anja M Gumpp  1 , Iris-Tatjana Kolassa  1 , Alexander Karabatsiakis  1   2
Affiliations

A history of childhood maltreatment is associated with altered DNA methylation levels of DNA methyltransferase 1 in maternal but not neonatal mononuclear immune cells

Rezan Nehir Mavioglu et al. Front Psychiatry. .

Abstract

Childhood maltreatment (CM) is associated with alterations in DNA methylation (DNAm) especially in stress response genes. Due to the higher risk of overall health complications of individuals with a parental history of CM, intergenerational transmission of CM-associated DNAm changes has been investigated but remains unclear. In this study, we investigated if different severities of CM have any influence on the DNAm of DNA methyltransferase 1 (DNMT1), an important enzyme of the DNAm machinery, in immune and buccal cells of mother-newborn dyads. DNAm was assessed by mass spectrometry using immune cell DNA from mothers (N = 117) and their newborns (N = 113), and buccal cell DNA of mother-newborn dyads (N = 68 each). Mothers with a history of CM had lower mean methylation of DNMT1 in immune cells compared to the mothers without a CM history. CM status only influenced maternal DNMT1 gene expression when at least moderate CM was reported. Buccal cell DNAm was not associated with CM status. Maternal history of CM was not linked to any alterations in DNMT1 mean DNAm in any of the cell types studied in newborns. We conclude that the CM-associated alterations in DNMT1 DNAm might point to allostatic load and can be physiologically relevant, especially in individuals with more severe CM experiences, resulting in an activated DNA methylation machinery that might influence stress response genes. Our lack of significant findings in buccal cells shows the tissue-specific effects of CM on DNAm. In our sample with low to moderate maternal CM history, there was no intergenerational transmission of DNMT1 DNAm in newborns.

Keywords: DNA methylation; DNMT1; childhood maltreatment; early life adversity; intergenerational transmission.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
DNA methyltransferase 1 (DNMT1) mean DNA methylation (DNAm) and relative gene expression in peripheral blood mononuclear cells (PBMC) of the mothers. (A) Mothers with none to mild CM experiences (CMlow–) had higher DNMT1 mean DNAm compared to mothers with at least low CM experiences (CMlow+; p = 0.013). (B) Mothers with none to low CM experiences (CMmod–) had higher DNMT1 mean DNAm compared to mothers with at least moderate CM experiences (CMmod+; p = 0.040). (C) DNMT1 mean DNAm had a negative trend level correlation with Childhood Trauma Questionnaire (CTQ) sum score (rs = –0.167, p = 0.083). *p < 0.05.
FIGURE 2
FIGURE 2
DNA methyltransferase 1 (DNMT1) relative gene expression in peripheral blood mononuclear cells (PBMC) of the mothers. (A) There was no significant difference between CMlow– and CMlow+ mothers in terms of their DNMT1 relative gene expression levels. (B) CMmod– mothers had lower DNMT1 relative gene expression compared to CMmod+ mothers (p = 0.015). (C) DNMT1 relative gene expression did not have a significant correlation with CTQ sum score (rs = 0.034, p = 0.782). (D) DNMT1 relative gene expression did not have a significant correlation with DNMT1 mean DNAm (rs = –0.012, p = 0.921). *p < 0.05.
FIGURE 3
FIGURE 3
The association between NR3C1 mean DNA methylation (DNAm) and DNMT1 DNAm and relative gene expression in peripheral blood mononuclear cells (PBMC) of the mothers. (A) DNMT1 mean DNAm did not have a significant correlation with NR3C1 exon 1F mean DNAm (rs = 0.031, p = 0.752). (B) DNMT1 relative gene expression had a positive correlation with NR3C1 exon 1F mean DNAm (rs = 0.444, p < 0.001).
FIGURE 4
FIGURE 4
DNA methyltransferase 1 (DNMT1) mean DNA methylation (DNAm) in buccal cells (BC) of the mothers. (A,B) DNMT1 mean DNA methylation did not differ in mothers categorized with their childhood maltreatment (CM) experiences depending on the low cut-off (CMlow– versus CMlow+) or moderate cut-off (CMmod– versus CMmod+). (C) DNMT1 mean DNAm did not have a significant correlation with CTQ sum score (rs = –0.086, p = 0.504). (D) There was no significant relationship between DNMT1 mean DNAm in immune and buccal cells (rs = –0.006, p = 0.965).
FIGURE 5
FIGURE 5
DNA methyltransferase 1 (DNMT1) mean DNA methylation (DNAm) in umbilical cord blood mononuclear cell (UBMC) of the newborns. (A,B) DNMT1 mean DNA methylation did not differ in newborns with a maternal history of childhood maltreatment (CM) experiences depending on the low cut-off (CMlow– versus CMlow+) or moderate cut-off (CMmod– versus CMmod+). (C) DNMT1 mean DNAm did not have a significant correlation with maternal CTQ sum score (rs = –0.042, p = 0.662). (D) There was no significant correlation between DNMT1 mean DNAm of mothers and newborns (rs = 0.146, p = 0.143).
FIGURE 6
FIGURE 6
DNA methyltransferase 1 (DNMT1) mean DNA methylation (DNAm) in buccal cells (BC) of the newborns. (A,B) DNMT1 mean DNA methylation did not differ in newborns with a maternal history of childhood maltreatment (CM) experiences depending on the low cut-off (CMlow– versus CMlow+) or moderate cut-off (CMmod– versus CMmod+). (C) DNMT1 mean DNAm did not have a significant correlation with maternal CTQ sum score (rs = 0.84, p = 0.505). (D) There was no significant correlation between DNMT1 mean DNAm of mothers and newborns (rs = 0.061, p = 0.647).
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