The relationship of maternal and child methylation of the glucocorticoid receptor NR3C1 during early childhood and subsequent child psychopathology at school-age in the context of maternal interpersonal violence-related post-traumatic stress disorder.

Autor:	Cordero MI; Department of Psychology, Manchester Metropolitan University, Manchester, United Kingdom., Stenz L; Department of Genetic Medicine and Development, University of Geneva Faculty of Medicine, Geneva, Switzerland., Moser DA; Child and Adolescent Psychiatry Service, Lausanne University Hospital, Lausanne, Switzerland., Rusconi Serpa S; Department of Psychology, University of Geneva Faculty of Psychology, Social Science and Education, Geneva, Switzerland., Paoloni-Giacobino A; Department of Genetic Medicine and Development, University of Geneva Faculty of Medicine, Geneva, Switzerland., Schechter DS; Child and Adolescent Psychiatry Service, Lausanne University Hospital, Lausanne, Switzerland.; Department of Psychiatry, Lausanne University Faculty of Biology and Medicine, Lausanne, Switzerland.; Department of Child and Adolescent Psychiatry, New York University Grossman School of Medicine, New York, NY, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in psychiatry [Front Psychiatry] 2022 Aug 19; Vol. 13, pp. 919820. Date of Electronic Publication: 2022 Aug 19 (Print Publication: 2022).
DOI:	10.3389/fpsyt.2022.919820
Abstrakt:	Introduction: Interpersonal violent (IPV) experiences when they begin in childhood and continue in various forms during adulthood often lead to chronic post-traumatic stress disorder (PTSD) that is associated in multiple studies with hypocortisolism and lower percentage of methylation of the promoter region of the gene coding for the glucocorticoid receptor (NR3C1). This prospective, longitudinal study examined the relationship of NR3C1 methylation among mothers with IPV-related PTSD and their toddlers and then looked at the relationship of maternal NR3C1 methylation and child psychopathology at school age. Methods: Forty-eight mothers were evaluated for life-events history and post-traumatic stress disorder via structured clinical interview when their children were ages 12-42 months (mean age 26.7 months, SD 8.8). Their children's psychopathology in terms of internalizing symptoms and externalizing behaviors was evaluated using the Child Behavior Checklist at ages 5-9 years (mean age 7 years, SD 1.1). Percentage of methylation for the NR3C1 gene promoter region was assessed from DNA extracted from maternal and child saliva using bisulfite pyrosequencing. Data analysis involved parametric and non-parametric correlations and multiple linear and logistic regression modeling. Results: Logistic regression models using child NR3C1 methylation as the dependent variable and maternal NR3C1 methylation and PTSD group status as predictors, as well as the interaction indicated that all three of these significantly predicted child NR3C1 methylation. These findings remained significant when controlling for child age, sex and maternal child abuse history. Overall, maternal NR3C1 methylation when children were toddlers was negatively and significantly associated with child externalizing behavior severity at school age. Discussion: We found that correlations between mothers and their children of NR3C1 methylation levels overall and at all individual CpG sites of interest were significant only in the IPV-PTSD group. The latter findings support that NR3C1 methylation in mothers positively and statistically significantly correlates with NR3C1 methylation in their children only in presence of IPV-PTSD in the mothers. This maternal epigenetic signature with respect to this glucocorticoid receptor is significantly associated with child behavior that may well pose a risk for intergenerational transmission of violence and related psychopathology. Competing Interests: 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. (Copyright © 2022 Cordero, Stenz, Moser, Rusconi Serpa, Paoloni-Giacobino and Schechter.)
Databáze:	MEDLINE
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