Meta-analysis is Consistent With Dopaminergic Perceptual and Cognitive Prediction Errors

Background: Evidence from candidate-gene and epigenome-wide studies suggests that epigenetic alterations may contribute to the demonstrated relationship between maternal prenatal depression and adverse offspring outcomes. Preliminary studies indicate that maternal prenatal depression may lead to “epigenetic age deceleration” in newborns, which in turn has been suggested as a risk factor for later developmental delays and psychopathology. Replication of these studies is warranted, as is further empirical testing of potentially co-occurring maternal risk factors including elevated rates of stress and antidepressant use in pregnancy. Methods: The present study examined the relationship between maternal prenatal exposures (i.e., depression, stress, and SSRI use) and offspring epigenetic age deceleration in a prospective cohort of mother-offspring dyads (n1⁄4303). Mothers were recruited from the Emory Women’s Mental Health Program in the first trimester of pregnancy and followed longitudinally until delivery. Offspring epigenetic age was determined via cord blood samples. Results: Findings indicated that maternal prenatal stress was unrelated to newborn epigenetic age (p1⁄40.51). Maternal prenatal depression was associated with decelerated epigenetic age in newborns (p1⁄40.03), but this relationship was not significant when statistically controlling for maternal use of SSRIs (p1⁄40.41). Conversely, maternal SSRI use in pregnancy significantly predicted newborn epigenetic age deceleration over and above the influence of maternal depression (p1⁄40.001). Conclusions: These findings suggest that maternal prenatal SSRI use may significantly contribute to the previously documented associations between maternal prenatal depression and epigenetic age deceleration. Further studies are needed to examine how these epigenetic differences at birth may contribute to adverse outcomes in later development. Supported By: NIH Grants MD009746, MH088609, and MH68036; NSF Graduate Research Fellowship (to B. McKenna)