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In utero  exposures to environmental factors may result in persistent epigenetic modifications affecting normal development and susceptibility to chronic diseases in later life. We explored the relationship between exposure of the growing fetus to maternal depression or antidepressants and DNA methylation at two differentially methylated regions (DMRs) of the imprinted  Insulin-like Growth Factor 2  ( IGF2 ) gene. Aberrant DNA methylation at the  IGF2  and neighboring  H19  DMRs has been associated with deregulated  IGF2  expression, childhood cancers and several chronic diseases during adulthood. Our study population is comprised of pregnant mothers and their newborns (n = 436), as part of the Newborn Epigenetics Study (NEST). A standardized questionnaire was completed and medical record data were abstracted to ascertain maternal depression and antidepressive drug use. DMR methylation levels in umbilical cord blood leukocytes were quantified using pyrosequencing. From the 436 newborns, laboratory data were obtained for 356 individuals at the  IGF2  DMRs, and for 411 individuals at the  H19  DMRs; about half of each group was African American or Caucasian. While overall no association between depression and methylation profiles was found, we observed a significant hypermethylation of the  H19  DMRs in newborns of African American (n = 177) but not Caucasian (n = 168) mothers who reported the use of antidepressive drugs during pregnancy (β = +6.89, p = 0.01). Of note, our data reveal a race-independent association between smoking during pregnancy and methylation at the  IGF2  DMR (+3.05%, p = 0.01). In conclusion, our findings suggest a race-dependent response related to maternal use of antidepressants at one of the  IGF2  DMRs in the offspring.

clinical epigenetics

The effects of depression and use of antidepressive medicines during pregnancy on the methylation status of the IGF2 imprinted control regions in the offspring