• Rita T Amiel Castro, Elena Gardini, Stavros I Iliadis, Ulrike Ehlert, Theodora Kunovac Kallak, and Alkistis Skalkidou.
• Department of Clinical Psychology and Psychotherapy, University of Zurich, Institute of Psychology, Zurich, Switzerland.
• Ups. J. Med. Sci. 2024 Jan 1; 129.

BackgroundWe examined differences in DNA methylation patterns in the NR3C1 and FKBP5 genes in relation to personality vulnerability to depression, resilience, and perinatal depressive symptoms, whilst also considering possible moderating effects of childhood traumatic events.MethodsN = 160 perinatal women were assessed at late pregnancy and 1 year postpartum for personality vulnerability to depression, resilience, depressive symptoms, and childhood traumatic events with self-reported questionnaires. NR3C1 and FKBP5 methylation markers were analyzed via sodium bisulfite sequencing. Associations of methylation markers with the above mentioned variables were tested using multivariable regressions.ResultsNR3C1 methylation at CpGs 1, 4 and average methylation sites were negatively associated with resilience; NR3C1 methylation at CpG 2 was positively associated with postpartum depressive symptoms; methylation at CpG 4 was positively associated with prenatal depressive symptoms. The interaction between current distress due to interpersonal traumatic events and NR3C1 CpG sites in relation to personality vulnerability was significant on CpG sites 3 and 4, whereas the interaction between current distress due to total traumatic events and NR3C1 in relation to personality vulnerability was significant on CpG site 2. FKBP5 showed no significant associations with the outcomes.ConclusionsThis study identified associations between NR3C1 methylation and resilience as well as perinatal depressive symptoms. Interestingly, an interaction between early trauma and personality vulnerability was noted. Our findings on these specific DNA methylation markers may, if replicated and integrated into risk prediction models, contribute to early diagnosis of mothers at risk, targeted health promotion, and early interventions.© 2024 The Author(s). Published by Upsala Medical Society.

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