Abstract
BackgroundPrenatal and early postnatal exposure to maternal depression may “program” childhood behavior via epigenetic processes such as DNA methylation. Methylenetetrahydro-folate reductase (MTHFR) is an important enzyme in the generation of methyl groups for DNA methylation. The common MTHFR C677T variant is associated with depression in men and non-pregnant women, and with global changes in DNA methylation. This study investigated the effect of maternal MTHFR C677T genotype on antenatal maternal mood, and their impact on the gene-specific methylation in pregnant women and their newborn infants. The methylation status of SLC6A4, which encodes the transmembrane serotonin transporter, and BDNF, which encodes brain derived neurotrophic factor, were assessed because of their potential role in behaviour.Methods/Principal FindingsDepressed mood was assessed by the Edinburgh Postnatal Depression Scale (EPDS) and the Hamilton Rating Scale for Depression (HAM-D) in women (n = 82, all taking folate) during the 2nd and 3rd trimesters of pregnancy. The methylation status of SLC6A4 and BDNF were assessed in 3rd trimester maternal peripheral leukocytes and in umbilical cord leukocytes collected from their infants at birth. Women with the MTHFR 677TT genotype had greater 2nd trimester depressed mood (p<0.05). Increased 2nd trimester maternal depressed mood (EPDS scores) was associated with decreased maternal and infant SLC6A4 promoter methylation (p<0.05), but had no effect on BDNF promoter methylation.ConclusionsThese findings show that the MTHFR C677T variant is associated with greater depressed mood during pregnancy. We further showed that prenatal exposure to maternal depressed mood affects gene-specific DNA methylation patterns. These findings support the concept that alterations in epigenetic processes may contribute to developmental programming of behaviour by maternal depression.
Highlights
15% of mothers experience mood disturbances during pregnancy and up to one third are treated with a serotonin reuptake inhibitor antidepressant (SRI) medication [1]
These findings show that the Methylenetetrahydro-folate reductase (MTHFR) C677T variant is associated with greater depressed mood during pregnancy
We recently reported an association between exposure to increased 3rd trimester maternal depressed mood and NR3C1 promoter methylation in newborn infants, and HPA stress reactivity at 3 months [7], even when mothers had been treated with a selective serotonin reuptake inhibitor antidepressant
Summary
15% of mothers experience mood disturbances during pregnancy and up to one third are treated with a serotonin reuptake inhibitor antidepressant (SRI) medication [1]. Studies in a rodent model have shown that variations in early life experience (maternal care over the first week of life) is associated with decreased HPA stress responsivity in early infancy, and involves changes in the methylation status of the hippocampal glucocorticoid receptor (GR) gene (Nr3c1) and Nr3c1 expression [6]. This phenomena has been demonstrated in humans. The methylation status of SLC6A4, which encodes the transmembrane serotonin transporter, and BDNF, which encodes brain derived neurotrophic factor, were assessed because of their potential role in behaviour
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