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Chunk #31 — Developmental Stress Exposure — Gestational stressors

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Epigenetic mechanisms in alcohol- and adversity-induced developmental origins of neurobehavioral functioning.
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Because glucocorticoid receptors (GRs) play a regulatory role in HPA axis functionality and negative feedback (Herman et al., 2012) and altered levels of GRs have been associated with anxiety and depression (Ridder et al., 2005; Yehuda et al., 1993; Yehuda et al., 1991), research has focused on the methylation patterns of NR3C1, which codes for the GR protein in humans. Numerous studies have found increased methylation of NR3C1 and concomitant reduced gene expression with gestational stress exposure. For example, women pregnant during the Tutsi genocide and their children have reduced levels of cortisol, increased mineralocorticoid receptor levels, increased methylation of NR3C1 in leukocytes, and reduced GR levels (Perroud et al., 2014). Psychosocial stress (i.e. exposure to war) incurred by the mother during gestation was positively correlated with NR3C1 methylation in the umbilical cord blood of offspring, an effect that was not observed in methylation of the mother’s blood suggesting this was reflective of the intrauterine environment (Mulligan et al., 2012). Stress was also negatively correlated with newborn birthweight (Mulligan et al., 2012). A similar effect was observed with intimate partner