Depression and glucocorticoid regulation during pregnancy: A pilot study of NR3C1 methylome profiling
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Date
2024-05
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The Ohio State University
Abstract
Introduction: One of every five pregnant individuals are diagnosed with prenatal depression, signifying a maternal mental health crisis. However, little is known about how depressive symptoms affect maternal biology in ways that are pertinent to the health of the pregnancy. In this pilot study, we examined associations among depression diagnoses, depressive symptoms during pregnancy, prenatal glucocorticoid levels, and the epigenetic regulation of NR3C1, the glucocorticoid receptor gene. NR3C1 plays a key role in transmitting cellular signals in response to psychosocial stress and differential expression of NR3C1 has been previously linked to poor birth outcomes. Methods: The parent study enrolled 96 pregnant individuals at 28 weeks 0 days to 32 weeks 6 days of pregnancy, of which we focus on 16 with available epigenome-wide DNA methylation data. All participants completed questionnaires, including the Center for Epidemiological Studies-Depression (CES-D) inventory. Peripheral whole blood was collected, and leukocyte DNA methylation was quantified across approximately 850K cytosine-guanine dinucleotides. After birth, clinical data was abstracted from the medical record. We examined DNA methylation of the 70 dinucleotides in proximity to the NR3C1 gene, identifying dinucleotides with suggestion of a potential association with depression diagnosis, depressive symptoms during pregnancy, and/or prenatal glucocorticoid (i.e., cortisol) levels (α=0.20). Results: Participants (n=16) averaged 25.3 years of age (SD 4.4, range 20-33). Most participants completed some college (n=9) and were multiparous (n=13). Half of participants were nonsmokers (n=8) while half reported smoking in early pregnancy (n=8). Controlling for maternal age, education, smoking status, parity, fetal sex, and white blood cell count, levels of DNA methylation at 13, 7, and 15 cytosine-guanine dinucleotides showed suggested associations with depression diagnosis, depressive symptoms during pregnancy, and prenatal glucocorticoid levels, respectively. Only two dinucleotides were identified more than once. A depression diagnosis and higher prenatal glucocorticoid levels showed suggestive associations with the methylation of cg14621978 (z=1.33, p=0.182; t=1.95, p=0.099, respectively) and cg01751279 (z=1.55, p=0.121; t=-2.03, p=0.088, respectively). Conclusions: In a small pilot study, our findings suggest that prenatal depressive symptoms may shape how the body responds to psychosocial stress and stress hormones. While more work remains to clarify the relationships among depression diagnoses, depressive symptoms, and glucocorticoid regulation during pregnancy, this may provide a unique opportunity to identify targets for the promotion of maternal-infant health.
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Keywords
Depression, glucocorticoid levels, NR3C1, pregnancy