DNA methylation in blood cells is associated with cortisol levels in offspring of mothers who had prenatal post‐traumatic stress disorder

Fransquet, Peter; Hjort, Line; Rushiti, Feride; Wang, Shr‐Jie; Krasniqi, Sebahate P; Çarkaxhiu, Selvi I; Arifaj, Dafina; Devaja, Vjosa; Salihu, Mimoza; Abdullahu‐Leku, Nazmie; Ryan, Joanne

doi:10.1002/smi.3131

Cited by 13 publications

(7 citation statements)

References 93 publications

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“…The current study finding of the association of BDNF DNA M with HCC supplements the previous findings (Unternaehrer et al, 2012;Zhou et al, 2023) by demonstrating that the level of BDNF DNA M in young adults increased in accordance with the HPA axis activity on a long-term basis. In regard to the relationship between BDNF DNA M and cortisol, BDNF DNA M was reported to be positively associated with morning cortisol levels in the offspring of mothers diagnosed with PTSD during pregnancy (Fransquet et al, 2022). The current study finding of the association of BDNF DNA M with HCC was at least partly in line with the previous findings (Fransquet et al, 2022).…”

Section: Discussionsupporting

confidence: 90%

Association of hair cortisol concentration with brain‐derived neurotrophic factor gene methylation: The role of sex as a moderator

Li,

Kong,

Park

et al. 2024

Stress and Health

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Hair cortisol concentration (HCC) reflects the long‐term activity of the hypothalamus‐pituitary‐adrenal (HPA) axis in response to stress. Brain‐derived neurotrophic factor DNA methylation (BDNF DNAM) may affect HCC, and sex and Val66Met may contribute to this association. Thus, the aim of this study was to investigate the associations between HCC and Brain‐derived neurotrophic factor (BDNF) DNAM, and the moderating effects of Val66Met and sex. We recruited 191 healthy young participants (96 women, mean age 23.0 ± 2.6 years) and collected body samples to evaluate HCC, and to determine BDNF DNAM and Val66Met genotypes. We analyzed the effects of BDNF DNAM, sex, and Val66Met on HCC. We also evaluated the associations between BDNF DNAM and HCC in groups separated by sex and genotypes. We found a marked association of BDNF DNAM with HCC across men and women. After dividing the data by sex, a positive correlation of HCC with BDNF DNAM was found only in women. There was no substantial moderation effect of Val66Met genotypes on the association between BDNF DNAM and HCC. Therefore, BDNF DNAM was found to have positive association with HCC only in healthy young women, indicating that sex moderates the association of BDNF DNAM with long‐term HPA axis activity.

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Section: Discussionsupporting

confidence: 90%

Association of hair cortisol concentration with brain‐derived neurotrophic factor gene methylation: The role of sex as a moderator

Li,

Kong,

Park

et al. 2024

Stress and Health

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“…Corroborating prior studies (Fransquet et al, 2022;Muller et al, 2022), we wanted to prove ectopic expression of GCrelated genes due to PS was associated with increased DNA methylation of 11β-HSD2, P-gp, FKBP5, NR3C1 in the placenta. On the basis of RRBS results, MethylTarget technology was used to verify the methylation level of cytosine in all CpG dinucleotides in the target region of candidate genes for the differential methylation sites and regions of placental GC barrier related genes P-gp (abcb1a) and FKBP5.…”

Section: Discussionmentioning

confidence: 98%

Prenatal stress increases corticosterone levels in offspring by impairing placental glucocorticoid barrier function

Liu,

Wang,

Zhu

et al. 2023

Preprint

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Background: Exposure to high cortisol levels in fetus of prenatal stress (PS) has adverse effects on growth, which is related to placental glucocorticoid (GC) barrier. DNA methylation is a potential prenatal planning mechanism in embryonic stage, however, the epigenetic regulation of placental GC barrier related genes on the PS resulting higher GC is unclear. This study was to test the hypothesis that PS would elevate cortisol which was associated with GC-related placenta genes (11β-HSD2, P-gp, NR3C1, and FKBP5) based on the DNA methylation. Method: PS model was established by chronic unpredictable mild stress (CUMS). DNA methylation in GC-related genes was analyzed using reduced representation bisulfite sequencing (RRBS) and confirmed results using MethylTarget™ sequencing. The genes expression were subjected to qRT-PCR and Western blot. Results: Offspring of PS had increased plasma corticosterone levels. GC-related gene (P-gp(abcb1a) and FKBP5) were identified by RRBS. We further verified DNA methylation and gene expression, including 43 differentially methylated sites and 2 differentially methylated regions. We found P-gp was hypermethylation and low expression, FKBP5 was hypermethylation low translational and high transcriptional levels. The expressions of 11β-HSD2 decreased, the NR3C1 mRNA expression was inhibited, and the protein expression increased. Discussion:This study provides an exploratory result: PS disrupts the placental GC barrier through hypermethylation and aberrant expression of GC-related genes, resulting in high corticosterone level in offspring, affecting growth and development. However, the molecular mechanism by which PS regulates the placental GC barrier remains to be further determined.

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“…In two other studies, community/neighbourhood disadvantage was linked to significant differences in DNA methylation of genes implicated in stress reactivity, inflammation, and neurodevelopment [ 65 , 66 ]. Furthermore, among offspring born to mothers with prenatal post-traumatic stress disorder (PTSD), DNA methylation has been associated with cortisol levels [ 67 ]. Indeed, when they compared offspring of mothers with PTSD with those without, offspring had different blood epigenome-wide methylation and fasting cortisol levels.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, when they compared offspring of mothers with PTSD with those without, offspring had different blood epigenome-wide methylation and fasting cortisol levels. Specifically, among the offspring of mothers who suffered PTSD, methylation at several CpG sites within the hypothalamic–pituitary–adrenal (HPA) axis genes, FRMD4A, FBXL2, CHD4 , and CCDC174 were associated with higher cortisol levels, compared to the non-PTSD group [ 67 ].…”

Section: Discussionmentioning

confidence: 99%

Maternal adverse childhood experiences (ACEs) and offspring imprinted gene DMR methylation at birth

Vidal,

Sosnowski,

Marchesoni

et al. 2023

Epigenetics

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Adverse childhood experiences (ACEs) contribute to numerous negative health outcomes across the life course and across generations. Here, we extend prior work by examining the association of maternal ACEs, and their interaction with financial stress and discrimination, with methylation status within eight differentially methylated regions (DMRs) in imprinted domains in newborns. ACEs, financial stress during pregnancy, and experience of discrimination were self-reported among 232 pregnant women. DNA methylation was assessed at PEG10 / SGCE, NNAT, IGF2, H19, PLAGL1 , PEG3 , MEG3-IG , and DLK1/MEG3 regulatory sequences using pyrosequencing. Using multivariable linear regression models, we found evidence to suggest that financial stress was associated with hypermethylation of MEG3-IG in non-Hispanic White newborns; discrimination was associated with hypermethylation of IGF2 and NNAT in Hispanic newborns, and with hypomethylation of PEG3 in non-Hispanic Black newborns. We also found evidence that maternal ACEs interacted with discrimination to predict offspring PLAGL1 altered DMR methylation, in addition to interactions between maternal ACEs score and discrimination predicting H19 and SGCE/PEG10 altered methylation in non-Hispanic White newborns. However, these interactions were not statistically significant after multiple testing corrections. Findings from this study suggest that maternal ACEs, discrimination, and financial stress are associated with newborn aberrant methylation in imprinted gene regions.

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DNA methylation in blood cells is associated with cortisol levels in offspring of mothers who had prenatal post‐traumatic stress disorder

Cited by 13 publications

References 93 publications

Association of hair cortisol concentration with brain‐derived neurotrophic factor gene methylation: The role of sex as a moderator

Association of hair cortisol concentration with brain‐derived neurotrophic factor gene methylation: The role of sex as a moderator

Prenatal stress increases corticosterone levels in offspring by impairing placental glucocorticoid barrier function

Maternal adverse childhood experiences (ACEs) and offspring imprinted gene DMR methylation at birth

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