LAUSR

Can traumatic experiences occurring before conception influence fetal development? In this issue of Biological Psychiatry, Moog et al. (1) report diminished intracranial volume and cortical gray matter in newborns of mothers exposed to childhood maltreatment, suggesting that this may be the case. The importance of the question is matched by the complexity involved in parsing out maternal influences—those originating at preconception and lasting throughout pregnancy—from postnatal maternal factors and other experiences of the child. Neuroimaging of neonates removes complications of the postnatal environment, allowingadeeper focuson theassociationbetween postdelivery maternal phenotype and fetal neurodevelopment. The findingsofMooget al. (1) are consistentwith previous reports ofmaternal influences on fetal neurodevelopment using neonatal neuroimaging (2), but they raise questions regarding the origin of these effects and its moderators. There is, of course, great interest in the hypothesis that intergenerational transmission occurs as a result of traumainduced epigenetic effects that may include alterations to the germline. These epigenetic changes might then be maintained through embryogenesis or re-established after conception and influence the intrauterine and placental environment (3). Although no direct evidence links trauma-induced epigenetic changes in oocytes to postconception epigenetic changes in either the fetus or the newborn, findings from rodent studies demonstrating epigenetically inherited changes in the sperm of offspring with paternal stress exposure indicate that this explanation is at least biologically feasible (4). That said, the issue here is that of “non–DNA sequence–based intergenerational transmission,” for which there are alternative mechanisms (e.g., prion proteins, transposons, RNAs) (3). Nongenetic inheritance should not necessarily be assumed to be epigenetic. Fetal development might be affected by an interaction between maternal childhood trauma exposure, maternal phenotype, and intrauterine sources of variation, including those mediated through the placenta (5). The placenta, a fetal tissue, reflects both maternal and fetal signals and is an important site for reciprocal transmission. Fetal biology may therefore partially reflect a response to intrauterine signals originating from enduring maternal trauma–induced cellular changes that affect fetal growth and development. This may explain why childhood maltreatment advances the age of puberty and is associated with enduring endocrine effects, including those on hypothalamic-pituitary-gonadal function (6). Although the study was underpowered for mediational analysis, the authors make a commendable attempt to control