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Pregnancy associated epigenetic markers of inflammation predict depression and anxiety symptoms in response to discrimination.

ABSTRACT: Latina mothers, who have one of the highest fertility rates among ethnic groups in the United States (US), often experience discrimination. Psychosocial influences during pregnancy, such as discrimination stress, promotes inflammation. However, the role of epigenetic markers of inflammation as a mediator between, and predictor of, maternal discrimination stress and neuropsychiatric outcomes has not been extensively studied. The current study investigates the role of DNA methylation at FOXP3 Treg-cell-specific demethylated region (TSDR), as a marker of regulatory T (Treg) cells that are important negative regulators of inflammation, and the promoter of tumour necrosis factor-alpha (TNF-?) gene, an important pro-inflammatory cytokine, in relation to discrimination stress during pregnancy and depression and anxiety symptomatology. A sample of 148 Latina women residing in the US (mean age 27.6 years) were assessed prenatally at 24-32 weeks' gestation and 4-6 weeks postnatally for perceived discrimination exposure (Everyday Discrimination Scale, EDS), emotional distress (depression, anxiety, perinatal-specific depression), acculturation, and acculturative stress. DNA methylation levels at the FOXP3 and TNF? promoter regions from blood samples collected at the prenatal stage were assessed by bisulphite pyrosequencing. Regression analyses showed that prenatal EDS associated with postnatal emotional distress, depression and anxiety symptoms only in those individuals with higher than mean levels of FOXP3 TSDR and TNF? promoter methylation; no such significant associations were found in those with lower than mean levels of methylation for either. We further found that these relationships were mediated by TNF? only in those with high FOXP3 TSDR methylation, implying that immunosuppression via TNF? promoter methylation buffers the impact of discrimination stress on postpartum symptomatology. These results indicate that epigenetic markers of immunosuppression and inflammation play an important role in resilience or sensitivity, respectively, to prenatal stress.

SUBMITTER: Sluiter F

PROVIDER: S-EPMC7739167 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Pregnancy associated epigenetic markers of inflammation predict depression and anxiety symptoms in response to discrimination.

Sluiter Femke F Incollingo Rodriguez Angela C AC Nephew Benjamin C BC Cali Ryan R Murgatroyd Chris C Santos Hudson P HP

Neurobiology of stress 20201121

Latina mothers, who have one of the highest fertility rates among ethnic groups in the United States (US), often experience discrimination. Psychosocial influences during pregnancy, such as discrimination stress, promotes inflammation. However, the role of epigenetic markers of inflammation as a mediator between, and predictor of, maternal discrimination stress and neuropsychiatric outcomes has not been extensively studied. The current study investigates the role of DNA methylation at <i>FOXP3</ ...[more]

PMID: 33344726

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Project description:BackgroudWe have recently reported that maternal prenatal pregnancy-related anxiety predicts preschoolers' emotional and behavioral development in a gender-dependent manner. This study aims to test for this gender-specific effect in a different cohort and investigate whether the gender difference was specific to placental methylation of genes regulating glucocorticoids.MethodsA total of 2405 mother-child pairs from the Ma'anshan Birth Cohort Study were included in present study. The maternal pregnancy-related anxiety symptoms were evaluated with the Pregnancy-Related Anxiety Questionnaire in the third trimester of pregnancy. Child neurobehavior was assessed with the Strengths and Difficulties Questionnaire at 4 years old. Placental methylation of FKBP5, NR3C1 and HSD11B2 genes was quantified using the MethylTarget approach in 439 pregnant women. After exploratory factor analysis, the associations between methylation factor scores and pregnancy-related anxiety and child neurobehavior were examined using logistic regression analysis.ResultsAfter controlling for confounding factors, pregnancy-related anxiety in the third trimester of pregnancy increased the risk of hyperactivity only in boys and emotional symptoms only in girls. Decreased scores of the factor characterized by FKBP5 methylation were associated with maternal pregnancy-related anxiety only in boys. Furthermore, increased scores of the factors characterized by NR3C1 and HSD11B2 methylation were associated with hyperactivity (NR3C1: adjusted OR = 1.80, 95%CI = 1.15-2.83) and emotional symptoms (HSD11B2: adjusted OR = 0.53, 95%CI = 0.29-0.97; NR3C1: adjusted OR = 1.64, 95%CI = 1.03-2.59) only in boys. However, the scores of the factor characterized by FKBP5, NR3C1 and HSD11B2 did not mediate the relationship between maternal pregnancy-related anxiety and preschoolers' emotional symptoms and hyperactivity.ConclusionsOur results suggested that pregnancy-related anxiety in the third trimester of pregnancy predicted preschoolers' emotional symptoms and hyperactivity in a gender-dependent manner. Although we did not find the mediation role of the placental methylation of genes regulating glucocorticoids, we found it was associated with both maternal pregnancy-related anxiety and preschoolers' emotional symptoms and hyperactivity in a gender-dependent manner.

Dataset Information

Pregnancy associated epigenetic markers of inflammation predict depression and anxiety symptoms in response to discrimination.

Publications

Pregnancy associated epigenetic markers of inflammation predict depression and anxiety symptoms in response to discrimination.

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