Mental Health
Maternal antenatal depression and offspring DNA methylation Diane Putnick* Diane Putnick Putnick Putnick Putnick Putnick Putnick Eunice Kennedy Shriver National Institute of Child Health and Human Development
Antenatal depression may affect child development through prenatal programming of the Hypothalamic-Pituitary-Adrenal axis by epigenetic modifications. Research on the link between antenatal depression and alterations in offspring DNA methylation is sparse and inconsistent. We aimed to test the association between maternal antenatal depression and offspring DNA methylation in neonatal and middle childhood periods.
Moderate to severe maternal antenatal depression was identified via a combination of diagnosis codes from outpatient and inpatient encounters during pregnancy and self-reported symptom severity on birth certificates. Offspring DNA methylation was quantified from dried blood spot and venous blood samples in the neonatal and middle childhood periods, respectively. Robust linear regression models with antenatal depression as the exposure and CpG M-values as outcomes were run adjusted for covariates and corrected for false discovery rate (FDR).
Of 733 mothers with available data in the neonatal period, 53 (7%) experienced moderate to severe antenatal depression. In middle childhood, 15 (9%) of the 161 mothers with available data experienced moderate to severe antenatal depression. In the neonatal period, no probes passed FDR correction. In middle childhood (Table 1), antenatal depression was associated with hypomethylation at two probes after adjustment and FDR correction: cg06112204 (in MAD1L1; β=-1.68, SE=0.29) and cg17830140 (in POLRMT, β=-1.94, SE=0.36). Both probes had a similar direction and magnitude when adjusting postnatal depression (β=-1.71, SE=0.34 and β=-1.78, SE=0.42, respectively). cg06112204 was also hypomethylated in the neonatal sample (β=-0.49, SE=0.21), but cg17830140 was not (β=0.07, SE=0.22).
Hypomethylation in the MAD1L1 gene has previously been associated with depression phenotypes in adolescents and adults, lending credibility to the finding that antenatal depression is associated with hypomethylation of cg06112204 in offspring.
