Cited by 14Epigenetics and DNA MethylationIntimate Partner and Family ViolenceChild Abuse and Trauma

Methylation of the glucocorticoid receptor gene (NR3C1) in dyads mother-child exposed to intimate partner violence in Cameroon: Association with anxiety symptoms

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Wadji, Dany Laure, Morina, Naser, Martin-Soelch, Chantal, Wicky, Chantal·2023·PLOS ONE

Published version of a preprint

Abstract

Background: The glucocorticoid receptor (GR), which is encoded by the NR3C1 (Nuclear Receptor Subfamily 3 Group C Member 1) gene plays an important role in the modulation of the hypothalamic-pituitary-adrenal (HPA) axis activity by providing feedback regulation which allows termination of the stress response. Little is known about epigenetic programming at the level of NGFI-A (nerve growth factor-inducible protein A) putative binding site (CpG) of the NR3C1 exon 1F in dyads mother-child exposed to intimate partner violence (IPV) more specifically in an unstudied region such as the sub-Saharan Africa where levels of violence are very high. Objective: Examine NR3C1 exon 1F methylation in response to IPV and possible association with cortisol concentration and mental health. Method: We recruited 20 mother–child dyads exposed to IPV and a control group of 20 mother–child dyads not exposed to IPV. We administered self-reported questionnaires to measure mother’s mental health and collected saliva samples for cortisol dosage and bisulfite sequencing of DNA methylation. Results: Regarding the mothers, our results showed a significant difference in methylation level at CpG 16–21 sites of the NR3C1 exon 1F promoter region between the groups. In the exposed group as compared to the control group, there was a significant positive association between the level of methylation at CpG 16–21 sites and mother’s mental health in particular anxiety symptoms. However, we did not find any significant correlation between methylation level and cortisol concentration. In children, we did not find any significant results. Conclusion: This study highlights a NGFI-A putative binding site (CpG 16–21) that is more methylated in mothers exposed to IPV and which may have the potential to confer vulnerability for psychopathologies.

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  • Additional studies link IPV exposure to altered methylation of NR3C1, corresponding with differences in stress reactivity and anxiety-related symptoms.

    “Additional studies link IPV exposure to altered methylation of NR3C1, corresponding with differences in stress reactivity and anxiety-related symptoms (55).”

    From Epigenetic changes associated with multi-generational trauma: characterization, mechanisms, and therapeutics (2026) · cites this paper as [55]

    The Discussion reports different NR3C1 methylation at CpG 16–21 in IPV-exposed mothers and an association with their anxiety symptoms. The Results (Cortisol measures) find no significant cortisol difference between exposed and control groups, so this study does not establish corresponding differences in stress reactivity. (LLM, conf=0.88)

    Experimental — accuracy not yet measured
  • A substantial proportion of studies have focused on a limited number of stress-response genes, most notably FKBP5 and NR3C1.

    “A substantial proportion of studies have focused on a limited number of stress-response genes, most notably FKBP5 and NR3C1 (55, 65, 83, 84, 121, 129).”

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  1. [2]Anderson K, van Ee E. Mothers and Children Exposed to Intimate Partner Violence: A Review of Treatment Interventions. Int J Environ Res Public Health 2018. doi: 10.3390/ijerph15091955 30205465 PMC6163939 · DOI
  2. [3]Ahinkorah BO, Dickson KS, Seidu A-A. Women decision-making capacity and intimate partner violence among women in sub-Saharan Africa. Arch Public Health. 2018; 76: 5. doi: 10.1186/s13690-018-0253-9 29423218 PMC5787915 · DOI
  3. [4]Campbell JC. Health consequences of intimate partner violence. The Lancet. 2002; 359: 1331– 6. doi: 10.1016/S0140-6736(02)08336-8 11965295 · DOI · Paper page
  4. [6]Agüero JM, Herrera-Almanza C, Villa K. Do human capital investments mediate the intergenerational transmission of domestic violence? SSM Popul Health. 2022; 17: 100985. doi: 10.1016/j.ssmph.2021.100985 35024419 PMC8733314 · DOI
  5. [7]Wadji DL, Ketcha Wanda GJM, Wicky C, Morina N, Martin-Soelch C. From the Mother to the Child: The Intergenerational Transmission of Experiences of Violence in Mother-Child Dyads Exposed to Intimate Partner Violence in Cameroon. J Interpers Violence. 2020; 37:NP3346-NP3376. doi: 10.1177/0886260520948148 32783520 · DOI
  6. [8]Roldós MI, Corso P. The economic burden of intimate partner violence in ecuador: setting the agenda for future research and violence prevention policies. West J Emerg Med. 2013; 14: 347– 53. doi: 10.5811/westjem.2013.2.15697 23930148 PMC3735382 · DOI
  7. [9]Dunlavey CJ. Introduction to the Hypothalamic-Pituitary-Adrenal Axis: Healthy and Dysregulated Stress Responses, Developmental Stress and Neurodegeneration. J Undergrad Neurosci Educ. 2018; 16: R59– R60. doi: 10.1186/1742-2094-11-34 30057514 PMC6057754 · DOI · Paper page
  8. [10]Bibi S, Shah M, Malik MO, Goosens KA. T3 is linked to stress-associated reduction of prolactin in lactating women. J Neuroendocrinol. 2021; 33: e13003. doi: 10.1111/jne.13003 34241933 · DOI
  9. [11]Mourtzi N, Sertedaki A, Charmandari E. Glucocorticoid Signaling and Epigenetic Alterations in Stress-Related Disorders. Int J Mol Sci 2021. doi: 10.3390/ijms22115964 34073101 PMC8198182 · DOI
  10. [12]Hinds JA, Sanchez ER. The Role of the Hypothalamus–Pituitary–Adrenal (HPA) Axis in Test-Induced Anxiety: Assessments, Physiological Responses, and Molecular Details. Stresses. 2022; 2: 146– 55. doi: 10.3390/stresses2010011 · DOI
  11. [13]Farrell C, Doolin K, O’ Leary N, Jairaj C, Roddy D, Tozzi L, et al. DNA methylation differences at the glucocorticoid receptor gene in depression are related to functional alterations in hypothalamic-pituitary-adrenal axis activity and to early life emotional abuse. Psychiatry Res. 2018; 265: 341– 8. doi: 10.1016/j.psychres.2018.04.064 29793048 · DOI · Paper page
  12. [14]Klatzkin RR, Baldassaro A, Rashid S. Physiological responses to acute stress and the drive to eat: The impact of perceived life stress. Appetite. 2019; 133: 393– 9. doi: 10.1016/j.appet.2018.11.019 30472407 · DOI
  13. [15]Borrow AP, Heck AL, Miller AM, Sheng JA, Stover SA, Daniels RM, et al. Chronic variable stress alters hypothalamic-pituitary-adrenal axis function in the female mouse. Physiol Behav. 2019; 209: 112613. doi: 10.1016/j.physbeh.2019.112613 31299374 PMC6693655 · DOI · Paper page
  14. [16]Pinto RJ, Correia-Santos P, Costa-Leite J, Levendosky AA, Jongenelen I. Cortisol awakening response among women exposed to intimate partner violence. Psychoneuroendocrinology. 2016; 74: 57– 64. doi: 10.1016/j.psyneuen.2016.08.024 27587076 · DOI
  15. [17]Wadji DL, Gaillard C, Ketcha Wanda GJM, Wicky C, Morina N, Martin-Soelch C. HPA-axis activity and the moderating effect of self-esteem in the context of intimate partner violence in Cameroon. Eur J Psychotraumatol. 2021; 12: 1930897. doi: 10.1080/20008198.2021.1930897 34290846 PMC8279150 · DOI
  16. [18]Boeckel MG, Viola TW, Daruy-Filho L, Martinez M, Grassi-Oliveira R. Intimate partner violence is associated with increased maternal hair cortisol in mother-child dyads. Compr Psychiatry. 2017; 72: 18– 24. doi: 10.1016/j.comppsych.2016.09.006 27693887 · DOI
  17. [21]Tomas C, Newton J, Watson S. A review of hypothalamic-pituitary-adrenal axis function in chronic fatigue syndrome. ISRN Neurosci. 2013; 2013: 784520. doi: 10.1155/2013/784520 24959566 PMC4045534 · DOI
  18. [22]Clemens V, Bürgin D, Eckert A, Kind N, Dölitzsch C, Fegert JM, et al Hypothalamic-pituitary-adrenal axis activation in a high-risk sample of children, adolescents and young adults in residential youth care—Associations with adverse childhood experiences and mental health problems. Psychiatry Res. 2020; 284: 112778. doi: 10.1016/j.psychres.2020.112778 32004894 · DOI
  19. [23]Smith SM, Vale WW. The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress. Dialogues Clin Neurosci. 2006; 8: 383– 95. doi: 10.31887/DCNS.2006.8.4/ssmith 17290797 PMC3181830 · DOI · Paper page
  20. [25]Gjerstad JK, Lightman SL, Spiga F. Role of glucocorticoid negative feedback in the regulation of HPA axis pulsatility. Stress. 2018; 21: 403– 16. doi: 10.1080/10253890.2018.1470238 29764284 PMC6220752 · DOI · Paper page
  21. [26]Palma-Gudiel H, Córdova-Palomera A, Leza JC, Fañanás L. Glucocorticoid receptor gene (NR3C1) methylation processes as mediators of early adversity in stress-related disorders causality: A critical review. Neurosci Biobehav Rev. 2015; 55: 520– 35. doi: 10.1016/j.neubiorev.2015.05.016 26073068 · DOI · Paper page
  22. [27]Assis Pinheiro J de, Freitas FV, Borçoi AR, Mendes SO, Conti CL, Arpini JK, et al. Alcohol consumption, depression, overweight and cortisol levels as determining factors for NR3C1 gene methylation. Sci Rep. 2021; 11: 6768. doi: 10.1038/s41598-021-86189-z 33762648 PMC7990967 · DOI
  23. [28]Ostlund BD, Conradt E, Crowell SE, Tyrka AR, Marsit CJ, Lester BM. Prenatal Stress, Fearfulness, and the Epigenome: Exploratory Analysis of Sex Differences in DNA Methylation of the Glucocorticoid Receptor Gene. Front Behav Neurosci. 2016; 10: 147. doi: 10.3389/fnbeh.2016.00147 27462209 PMC4940423 · DOI
  24. [29]McGowan PO, Sasaki A, D’Alessio AC, Dymov S, Labonté B, Szyf M, et al. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci. 2009; 12: 342– 8. doi: 10.1038/nn.2270 19234457 PMC2944040 · DOI · Paper page
  25. [30]Chatzittofis A, Boström ADE, Ciuculete DM, Öberg KG, Arver S, Schiöth HB, et al. HPA axis dysregulation is associated with differential methylation of CpG-sites in related genes. Sci Rep. 2021; 11: 20134. doi: 10.1038/s41598-021-99714-x 34635736 PMC8505644 · DOI · Paper page
  26. [31]Suh JS, Fiori LM, Ali M, Harkness KL, Ramonas M, Minuzzi L, et al. Hypothalamus volume and DNA methylation of stress axis genes in major depressive disorder: A CAN-BIND study report. Psychoneuroendocrinology. 2021; 132: 105348. doi: 10.1016/j.psyneuen.2021.105348 34229186 · DOI
  27. [32]Parade SH, Ridout KK, Seifer R, Armstrong DA, Marsit CJ, McWilliams MA, et al. Methylation of the Glucocorticoid Receptor Gene Promoter in Preschoolers: Links With Internalizing Behavior Problems. Child Dev. 2016; 87: 86– 97. doi: 10.1111/cdev.12484 26822445 PMC4869528 · DOI
  28. [33]Daskalakis NP, Yehuda R. Site-specific methylation changes in the glucocorticoid receptor exon 1F promoter in relation to life adversity: systematic review of contributing factors. Front Neurosci. 2014; 8: 369. doi: 10.3389/fnins.2014.00369 25484853 PMC4240065 · DOI · Paper page
  29. [34]Berretta E, Guida E, Forni D, Provenzi L. Glucocorticoid receptor gene (NR3C1) methylation during the first thousand days: Environmental exposures and developmental outcomes. Neurosci Biobehav Rev. 2021; 125: 493– 502. doi: 10.1016/j.neubiorev.2021.03.003 33689802 · DOI
  30. [37]Serpeloni F, Nätt D, Assis SG de, Wieling E, Elbert T. Experiencing community and domestic violence is associated with epigenetic changes in DNA methylation of BDNF and CLPX in adolescents. Psychophysiology 2019. doi: 10.1111/psyp.13382 31059136 PMC7003421 · DOI · Paper page
  31. [38]Straus MA, Hamby SL, Boney-McCoy S, Sugarman DB. The revised Conflict Tactics Scales (CTS2): Development and preliminary psychometric data. Journal of Family Issues. 1996; 17: 283– 316.
  32. [40]Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983; 67: 361– 70. doi: 10.1111/j.1600-0447.1983.tb09716.x 6880820 · DOI · Paper page
  33. [41]Lepine JP, Godchau M, Brun P. Anxiety and depression in inpatients. The Lancet. 1985; 326: 1425– 6. doi: 10.1016/s0140-6736(85)92589-9 2867417 · DOI
  34. [42]Perroud N, Paoloni-Giacobino A, Prada P, Olié E, Salzmann A, Nicastro R, et al. Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: a link with the severity and type of trauma. Transl Psychiatry. 2011; 1: e59. doi: 10.1038/tp.2011.60 22832351 PMC3309499 · DOI · Paper page
  35. [44]Ewels P, Magnusson M, Lundin S, Käller M. MultiQC: summarize analysis results for multiple tools and samples in a single report. Bioinformatics. 2016; 32: 3047– 8. doi: 10.1093/bioinformatics/btw354 27312411 PMC5039924 · DOI · Paper page
  36. [46]Thorvaldsdóttir H, Robinson JT, Mesirov JP. Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration. Brief Bioinform. 2013; 14: 178– 92. doi: 10.1093/bib/bbs017 22517427 PMC3603213 · DOI · Paper page
  37. [47]Barturen G, Rueda A, Oliver JL, Hackenberg M. MethylExtract: High-Quality methylation maps and SNV calling from whole genome bisulfite sequencing data. F1000Res. 2013; 2: 217. doi: 10.12688/f1000research.2-217.v2 24627790 PMC3938178 · DOI
  38. [48]Pruessner JC, Kirschbaum C, Meinlschmid G, Hellhammer DH. Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change. Psychoneuroendocrinology. 2003; 28: 916– 31. doi: 10.1016/s0306-4530(02)00108-7 12892658 · DOI · Paper page
  39. [49]Cohen J. Statistical power analysis for the behavioral sciences. 2nd ed. New York, London: Psychology Press; Taylor & Francis Group; 1988.
  40. [50]Wu H-C, Wang Q, Chung WK, Andrulis IL, Daly MB, John EM, et al. Correlation of DNA methylation levels in blood and saliva DNA in young girls of the LEGACY Girls study. Epigenetics. 2014; 9: 929– 33. doi: 10.4161/epi.28902 24756002 PMC4143407 · DOI
  41. [51]Stalder T, Kirschbaum C, Kudielka BM, Adam EK, Pruessner JC, Wüst S, et al. Assessment of the cortisol awakening response: Expert consensus guidelines. Psychoneuroendocrinology. 2016; 63: 414– 32. doi: 10.1016/j.psyneuen.2015.10.010 26563991 · DOI · Paper page
  42. [52]Sikweyiya Y, Addo-Lartey AA, Alangea DO, Dako-Gyeke P, Chirwa ED, Coker-Appiah D, et al. Patriarchy and gender-inequitable attitudes as drivers of intimate partner violence against women in the central region of Ghana. BMC Public Health. 2020; 20: 682. doi: 10.1186/s12889-020-08825-z 32404153 PMC7222313 · DOI
  43. [53]Rani M, Bonu S, Diop-Sidibe N. An Empirical Investigation of Attitudes towards Wife-Beating among Men and Women in Seven Sub-Saharan African Countries. Afr J Reprod Health. 2004; 8: 116. doi: 10.2307/3583398 17348330 · DOI

Cited by

Sorted by citations

Authors
Wadji, D. L., Morina, N., Martin-Soelch, C., & Wicky, C.
Affiliations
  • University of Fribourg (CH)
  • University of Zurich (CH)
Corresponding author
Wadji, Dany Laure
Venue
PLOS ONE
Published
2023-04-06
Volume
18
Issue
4
Pages
e0273602
ISSN
1932-6203 (ISSN-L)
OpenAlex
W4362658281
Cited by
14
References
5
Citations by year
2026: 2 · 2025: 4 · 2024: 6 · 2023: 2
FWCI
1.25
Type
journal article
Language
en
Open access
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Swiss Government Excellence Scholarships (2018.0801)
  • Swiss National Science Foundation (P1FRP1_199872)
  • University of Fribourg Research Pool
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Social Sciences › Health › Intimate Partner and Family Violence
  • Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
Keywords
glucocorticoid receptor, NR3C1, DNA methylation, intimate partner violence, mother-child dyads, anxiety symptoms, cortisol, hypothalamic-pituitary-adrenal axis, epigenetic programming, maternal mental health, Cameroon
MeSH terms
Intimate Partner Violence, Anxiety, Cameroon, Female, Glucocorticoids, Humans, Hydrocortisone, Mother-Child Relations, Promoter Regions, Genetic, Receptors, Glucocorticoid, CpG Islands, DNA Methylation

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