Although animal models and correlational studies support a model of fetal programming as a mechanism in the transmission of risk for psychopathology from parents to children, the experimental studies that are required to empirically test the model with the human prenatal dyad are scarce. With a systematic review and meta-analysis of the literature, we critically examined the evidence regarding the neurobiological and behavioral changes in infants as a function of randomized clinical trials to prevent or reduce maternal depression during pregnancy, treating randomized clinical trials as experiments testing the fetal programming model. Based on 25 articles that met inclusion criteria, we found support for interventions designed to change maternal prenatal mood being associated with changes in offspring functioning, but with a very small effect size. Effect sizes ranged broadly, and were higher for younger children. The findings enhance understanding of putative mechanisms in the transmission of risk from women's prenatal depression to infants’ vulnerabilities to, and early signs of, the development of psychopathology. We note limitations of the literature and suggest solutions to advance understanding of how preventing or treating depression in pregnant women might disrupt the transmission of risk to the infants.

Psychotropic medication use and psychiatric symptoms during pregnancy each are associated with adverse neurodevelopmental outcomes in offspring. Commonly, studies considering medication effects do not adequately assess symptoms, nor evaluate children when the effects are believed to occur, the fetal period. This study examined maternal serotonin reuptake inhibitor and polypharmacy use in relation to serial assessments of five indices of fetal neurobehavior and Bayley Scales of Infant Development at 12 months in N = 161 socioeconomically advantaged, non-Hispanic White women with a shared risk phenotype, diagnosed major depressive disorder. On average fetuses showed the expected development over gestation. In contrast, infant average Bayley psychomotor and mental development scores were low (M = 84.10 and M = 89.92, range of normal limits 85–114) with rates of delay more than 2–3 times what would be expected based on this measure's normative data. Controlling for prenatal and postnatal depressive symptoms, prenatal medication effects on neurobehavioral development were largely undetected in the fetus and infant. Mental health care directed primarily at symptoms may not address the additional psychosocial needs of women parenting infants. Speculatively, prenatal serotonin reuptake inhibitor exposure may act as a plasticity rather than risk factor, potentially enhancing receptivity to a nonoptimal postnatal environment in some mother–infant dyads.

Associations between infants' frontal EEG asymmetry and temperamental negative affectivity (NA) across infants' first year of life and the potential moderating role of maternal prenatal depressive symptoms were examined prospectively in infants (n = 242) of mothers at elevated risk for perinatal depression. In predicting EEG, in the context of high prenatal depressive symptoms, infant NA and frontal EEG asymmetry were negatively associated at 3 months of age and positively associated by 12 months of age. By contrast, for low depression mothers, infant NA and EEG were not significantly associated at any age. Postnatal depressive symptoms did not add significantly to the models. Dose of infants' exposure to maternal depression mattered: infants exposed either pre- or postnatally shifted from a positive association at 3 months to a negative association at 12 months; those exposed both pre- and postnatally shifted from a negative association at 3 months to a positive association at 12 months. Prenatal relative to postnatal exposure did not matter for patterns of association between NA and EEG. The findings highlight the importance of exploring how vulnerabilities at two levels of analysis, behavioral and psychophysiological, co-occur over the course of infancy and in the context of mothers' depressive symptomatology.

Recent studies have focused on the behavioral and neurobiological sequella of exposure to early adverse events. We hypothesize that early adverse experiences result in an increased sensitivity to the effects of stress later in life and render an individual vulnerable to stress-related psychiatric disorders. This vulnerability may be mediated by persistent changes in corticotropin-releasing-factor (CRF)-containing neurons, the hypothalamic–pituitary–adrenal axis, and the sympathetic nervous system. We therefore present an overview of the CRF system and its role as a mediator in the development of the stress response, major depression, and posttraumatic stress disorder. The literature pertaining to behavioral and neurobiological alterations associated with exposure to early adverse life events in rodents, nonhuman primates, and humans is reviewed. We focus on animal models that precipitate depressive and anxiety symptoms while producing neuroendocrine alterations that mimic those seen in adults with those disorders. The literature integrating neurobiological and behavioral consequences of early life stress is also reviewed, focusing primarily on infants born to mothers with depression and on infants who were abused or neglected.