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. 2024 Sep 4:129.
doi: 10.48101/ujms.v129.10603. eCollection 2024.

Personality vulnerability to depression, resilience, and depressive symptoms: epigenetic markers among perinatal women

Rita T Amiel Castro  1 , Elena Gardini  1 , Stavros I Iliadis  2 , Ulrike Ehlert  1 , Theodora Kunovac Kallak #  2 , Alkistis Skalkidou #  2
Affiliations

Personality vulnerability to depression, resilience, and depressive symptoms: epigenetic markers among perinatal women

Rita T Amiel Castro et al. Ups J Med Sci. .

Abstract

Background: We 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.

Methods: N = 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.

Results: NR3C1 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.

Conclusions: This 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.

Keywords: Trauma; depressive symptoms; epigenetics; pregnancy; resilience.

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Conflict of interest statement

All authors confirm they have no conflicts of interests to declare. This work was funded by the University of Zurich Foundation for Research in Science and the Humanities (RAC and UE: STWF-18-019), the Swedish Research Council (AS: 523-2014-2342, 523-2014-07605, and 521-2013-2339), the Swedish Brain Foundation (AS: FO2022-0098), and the Marianne and Marcus Wallenberg Foundation (AS: MMW2011.0115).

Figures

Figure 1
Figure 1
The upper panel represents the diagram of the first exon in the NR3C1 promoter region. The lower panel depicts the NR3C1 exon 1F sequence, chr5 (hg19): 142,783,586–142,783,903 located in the 5′untranslated region of the NR3C1. CpG 1–4 correspond to CpG sites 37, 36, 26, and 16 described by Palma-Gudiel (37). Underlined sequences correspond to the primer’s positions.
Figure 2
Figure 2
The upper panel represents the FKBP5 locus including intron 7 GR. Black bars represent the 11 exons. The lower panel depicts the FKBP5 intron 7 sequence, chr6 (hg19): 35558441–35558783. The CpG sites are represented in bold boxes as described by Klengel et al. (18) In Klengel et al. and Yehuda et al. (10), our CpG 1 corresponds to their CpG 3, our CpG 2 corresponds to their CpG 4, our CpG 3 corresponds to their CpG 5, and our CpG 4 corresponds to their CpG 6. Underlined sequences correspond to the primer’s positions.
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