Maternal anxiety during pregnancy and newborn epigenome-wide DNA methylation

Sammallahti, Sara; Hidalgo, Andrea P. Cortes; Tuominen, Samuli; Malmberg, Anni; Mulder, Rosa H.; Brunst, Kelly J.; Alemany, Silvia; McBride, Nancy; Yousefi, Paul; Heiss, Jonathan; McRae, Nia; Page, Christian M.; Jin, Jianping; Pesce, Giancarlo; Caramaschi, Doretta; Rifas‐Shiman, Sheryl L.; Koen, Nastassja; Adams, Charleen D.; Magnus, Maria C; Baïz, Nour; Ratanatharathorn, Andrew; Czamara, Darina; Håberg, Siri E.; Colicino, Elena; Baccarelli, Andrea A.; Cárdenas, Andrés; DeMeo, Dawn L.; Lawlor, Debbie A.; Relton, Caroline L; Felix, Janine F.; IJzendoorn, M.H. van; Bakermans‐Kranenburg, Marian J.; Kajantie, Eero; Räikkönen, Katri; Sunyer, Jordi; Sharp, Gemma C; Houtepen, Lotte C; Nøhr, Ellen Aagaard; Sørensen, Thorkild I A; Téllez‐Rojo, Martha María; Wright, Robert O.; Annesi‐Maesano, Isabella; Wright, John; Hivert, Marie‐France; Wright, Rosalind J.; Zar, Heather J.; Stein, Dan J.; London, Stephanie J.; Cecil, Charlotte A.M.; Tiemeier, Henning; Lahti, Jari

doi:10.1038/s41380-020-00976-0

Cited by 29 publications

(24 citation statements)

References 59 publications

(70 reference statements)

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“…The first DMR containing 4 CpGs (cg01987516, cg07044859, cg17888390 and cg23904955) is located on chr10 in an intergenic region between the genes GOT1 and DQ372722 . Higher DNAm of cg01987516 has been previously related to maternal anxiety in umbilical cord blood [ 52 ]. Furthermore, cg23904955 has been negatively correlated with ethanol consumption per day over the course of a year during the blood sample collection in a European population [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of stressful life-events on DNA methylation in panic disorder and major depressive disorder

et al. 2022

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Background Panic disorder (PD) is characterized by recurrent panic attacks and higher affection of women as compared to men. The lifetime prevalence of PD is about 2–3% in the general population leading to tremendous distress and disability. Etiologically, genetic and environmental factors, such as stress, contribute to the onset and relapse of PD. In the present study, we investigated epigenome-wide DNA methylation (DNAm) in respond to a cumulative, stress-weighted life events score (wLE) in patients with PD and its boundary to major depressive disorder (MDD), frequently co-occurring with symptoms of PD. Methods DNAm was assessed by the Illumina HumanMethylation450 BeadChip. In a meta-analytic approach, epigenome-wide DNAm changes in association with wLE were first analyzed in two PD cohorts (with a total sample size of 183 PD patients and 85 healthy controls) and lastly in 102 patients with MDD to identify possible overlapping and opposing effects of wLE on DNAm. Additionally, analysis of differentially methylated regions (DMRs) was conducted to identify regional clusters of association. Results Two CpG-sites presented with p-values below 1 × 10−05 in PD: cg09738429 (p = 6.40 × 10−06, located in an intergenic shore region in next proximity of PYROXD1) and cg03341655 (p = 8.14 × 10−06, located in the exonic region of GFOD2). The association of DNAm at cg03341655 and wLE could be replicated in the independent MDD case sample indicating a diagnosis independent effect. Genes mapping to the top hits were significantly upregulated in brain and top hits have been implicated in the metabolic system. Additionally, two significant DMRs were identified for PD only on chromosome 10 and 18, including CpG-sites which have been reported to be associated with anxiety and other psychiatric phenotypes. Conclusion This first DNAm analysis in PD reveals first evidence of small but significant DNAm changes in PD in association with cumulative stress-weighted life events. Most of the top associated CpG-sites are located in genes implicated in metabolic processes supporting the hypothesis that environmental stress contributes to health damaging changes by affecting a broad spectrum of systems in the body.

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Section: Discussionmentioning

confidence: 99%

Effects of stressful life-events on DNA methylation in panic disorder and major depressive disorder

et al. 2022

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“…These null findings are consistent with previous EWAS investigations examining objective prenatal stressors like stressful life events and mood disorders with DNAm alterations in cord blood. 18 , 37 - 39 Previous candidate-gene studies of prenatal stress have focused largely on DNAm alternations in genes related to HPA-axis functioning, such as NR3C1 or FKBP5 . The secretion of systemic glucocorticoids (eg, increasing serum cortisol) is the product of the HPA-axis’s response to stressors.…”

Section: Discussionmentioning

confidence: 99%

Periconception and Prenatal Exposure to Maternal Perceived Stress and Cord Blood DNA Methylation

et al. 2022

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Background: Maternal prenatal stress is associated with physiologic and adverse mental health outcomes in the offspring, but the underlying biologic mechanisms are unknown. We examined the associations of maternal perceived stress, including preconception exposure, with DNA methylation (DNAm) alterations in the cord blood buffy coats of 358 singleton infants. Methods: Maternal perceived stress was measured prior to and throughout pregnancy in a cohort of women enrolled in Effects of Aspirin in Gestation and Reproduction Trial (EAGeR) trial. Perceived stress assessments based on a standardized Likert-scale were obtained in periconception (~2 months preconception and 2-8 weeks of gestation) and pregnancy (8-36 weeks of gestation). Cumulative perceived stress was estimated by calculating the predicted area under the curve of stress reported prior to and during pregnancy. DNAm was measured by the Infinium MethylationEPIC BeadChip. Multivariable robust linear regression was used to assess associations of perceived stress with individual CpG probes. Results: Based on a 0 to 3 scale, average reported preconception and early pregnancy stress were 0.76 (0.60) and 0.67 (0.50), respectively. Average mid- to late-pregnancy stress, based on a 0 to 10 scale, was 4.9 (1.6). Neither periconception nor pregnancy perceived stress were associated with individual CpG sites in neonatal cord blood (all false discovery rate [FDR] >5%). Conclusion: No effects of maternal perceived stress exposure on array-wide cord blood neonatal methylation differences were found.

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“…These different approaches have been recently summarized in two reviews and a meta-analysis (18, 35,36). When analyzing these studies, a general conclusion on what type of epigenetic signature is observed in prenatally stressed infants is di cult to draw since many methodological differences are still observed in terms of the type and timing of the prenatal insult studied, the age of the child and the tissue employed to detect DNA methylation.…”

Section: Discussionmentioning

confidence: 99%

Maternal-fetal Stress and Dna Methylation Signatures in Neonatal Saliva: an Epigenome-wide Association Study.

Antonelli

2022

Preprint

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Background Maternal stress before, during and after pregnancy has profound effects on the development and life-long function of the infant’s neurocognitive development. We hypothesized that the programming of the Central Nervous System (CNS), Hypothalamic Pituitary Axis (HPA) and Autonomic Nervous System (ANS) induced by prenatal stress (PS) is reflected in electrophysiological and epigenetic biomarkers. In this study, we aimed to find non-invasive epigenetic biomarkers of PS in the newborn salivary DNA. Results 738 pregnant women were screened for stress exposure using Cohen Perceived Stress Scale (PSS), 164 women were enrolled and 114 dyads were analyzed. Prenatal Distress Questionnaire (PDQ) was also administered to assess specific pregnancy worries. Transabdominal fetal Electrocardiograms (taECG) were recorded to derive coupling between maternal and fetal heart rates resulting in a “Fetal Stress Index” (FSI). Upon delivery, we collected maternal hair strands for cortisol measurements and newborn’s saliva for epigenetic analyses. DNA was extracted from saliva samples and DNA methylation was measured using EPIC Bead-Chip array (850k CpG sites). Linear regression was used to identify associations between PSS/PDQ/FSI/Cortisol and DNA methylation. We found epigenome-wide significant associations for 5 CpG with PDQ and cortisol at FDR < 5%. Three CpGs were annotated to genes (Illumina Gene annotation file): YAP1, TOMM20 and CSMD1 and two CpGs were located approximately lay at 50kb from SSBP4 and SCAMP1. In addition, two Differentiated Methylation regions (DMR) related to maternal stress measures PDQ and cortisol were found: DAXX and ARL4D. Conclusions Genes annotated to these CpGs were found to be involved in secretion and transportation, nuclear signaling, Hippo signaling pathways, apoptosis, intra-cellular trafficking and neuronal signaling. Moreover, some CpGs are annotated to genes related to autism, Post Traumatic Stress Disorder (PTSD) and schizophrenia. Early assessment of such non-invasive PS biomarkers will allow timelier detection of babies at risk and a more effective allocation of resources for early intervention programs to improve child development. A biomarker-guided early intervention strategy is the first step in the prevention of future health problems, reducing their personal and societal impact.

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Maternal anxiety during pregnancy and newborn epigenome-wide DNA methylation

Cited by 29 publications

References 59 publications

Effects of stressful life-events on DNA methylation in panic disorder and major depressive disorder

Effects of stressful life-events on DNA methylation in panic disorder and major depressive disorder

Periconception and Prenatal Exposure to Maternal Perceived Stress and Cord Blood DNA Methylation

Maternal-fetal Stress and Dna Methylation Signatures in Neonatal Saliva: an Epigenome-wide Association Study.

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