Maternal depression is associated with DNA methylation changes in cord blood T lymphocytes and adult hippocampi

Abstract

Depression affects 10–15% of pregnant women and has been associated with preterm delivery and later developmental, behavioural and learning disabilities. We tested the hypothesis that maternal depression is associated with DNA methylation alterations in maternal T lymphocytes, neonatal cord blood T lymphocytes and adult offspring hippocampi. Genome-wide DNA methylation of CD3+ T lymphocytes isolated from 38 antepartum maternal and 44 neonatal cord blood samples were analyzed using Illumina Methylation 450 K microarrays. Previously obtained methylation data sets using methylated DNA immunoprecipitation and array-hybridization of 62 postmortem hippocampal samples of adult males were re-analyzed to test associations with history of maternal depression. We found 145 (false discovery rate (FDR) q<0.05) and 2520 (FDR q<0.1) differentially methylated CG-sites in cord blood T lymphocytes of neonates from the maternal depression group as compared with the control group. However, no significant DNA methylation differences were detected in the antepartum maternal T lymphocytes of our preliminary data set. We also detected 294 differentially methylated probes (FDR q<0.1) in hippocampal samples associated with history of maternal depression. We observed a significant overlap (P=0.002) of 33 genes with changes in DNA methylation in T lymphocytes of neonates and brains of adult offspring. Many of these genes are involved in immune system functions. Our results show that DNA methylation changes in offspring associated with maternal depression are detectable at birth in the immune system and persist to adulthood in the brain. This is consistent with the hypothesis that system-wide epigenetic changes are involved in life-long responses to maternal depression in the offspring.

Prenatal loss of father during World War One is predictive of a reduced lifespan in adulthood

“…NR3C1 is not the only locus where DNA methylation is modified by maternal stress. Other methylation changes in offspring exposed to maternal depression were detectable in the immune system at birth and persisted until adulthood in the hippocampus, a known regulator of HPA activity (54).…”

The impact of psychological distress during pregnancy on the developing fetus: biological mechanisms and the potential benefits of mindfulness interventions

“…For example, a study by Rodney et al [48] found that infants whose mothers had experienced severe war stress during pregnancy had 212 differentially methylated CpG regions in cord blood, compared to non-exposed control infants. Nemoda et al [49] studied T lymphocyte methylation patterns in the neonatal cord blood of both infants whose mothers experienced prenatal depression and infants whose mothers did not experience prenatal depression. They found that infants in the prenatal depression group had 2520 differentially methylated CpG sites as compared to controls, and that 75.5% of these sites were hypomethylated.…”

Dopamine receptor D4 promoter hypermethylation increases the risk of drug addiction

“…A previous study on genome-wide DNA methylation profiling identified that DNA methylation levels were lower in patients with major depressive disorder compared with controls and that the majority of the methylated sites (85.7%) were located on the promoter CpG islands (34). Additionally, a previous study suggested that maternal depression is associated with DNA methylation changes in cord blood T lymphocytes and adult hippocampi (35). In the present study, a positive correlation between CpG5 methylation and depression-dejection was detected in heroin addicts, indicating that the DRD4 CpG5 methylation level may contribute to the onset of depression in heroin addicts.…”