Abstract 2754: Maternal use of antidepressants in pregnancy is associated with hypermethylation at the IGF2 imprinted control regions in the offspring in a race-dependent fashion

In utero exposures to environmental factors may result in persistent epigenetic modifications affecting normal development and susceptibility to chronic diseases in later life. We determined whether exposure of the growing fetus to maternal depression or antidepressants is associated with aberrant DNA methylation at two differentially methylated regions (DMRs) of the imprinted Insulin-like Growth Factor 2 (IGF2) gene, namely the DMRs upstream of the imprinted IGF2 promoters (IGF2 DMR) and the DMRs upstream of H19 (H19 DMR). Aberrant DNA methylation at these DMRs has been associated with deregulated IGF2 expression, childhood cancers and several chronic diseases during adulthood. Our study population comprises pregnant mothers and their newborns (n=436), recruited between 2005 and 2008 in Durham, NC. A standardized questionnaire was completed and medical record data were abstracted to ascertain prenatal and periconceptional depression and antidepressive drug use. DMR methylation percentages in umbilical cord blood leukocytes were quantified using pyrosequencing. While an association between depression and methylation profiles was not found, we discovered significant hypermethylation of the H19 DMRs in newborns of African American -but not Caucasian- mothers who were taking antidepressive drugs during pregnancy (β=+6.89, p=0.01). Our findings suggest that changes in the IGF2/H19-domain methylation in response to maternal exposure to antidepressants are race-dependent. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2754. doi:10.1158/1538-7445.AM2011-2754