Prenatal Developmental Origins of Future Psychopathology: Mechanisms and Pathways

Abstract

The developmental origins of health and disease hypothesis applied to neurodevelopmental outcomes asserts that the fetal origins of future development are relevant to mental health. There is a third pathway for the familial inheritance of risk for psychiatric illness beyond shared genes and the quality of parental care: the impact of pregnant women's distress—defined broadly to include perceived stress, life events, depression, and anxiety—on fetal and infant brain–behavior development. We discuss epidemiological and observational clinical data demonstrating that maternal distress is associated with children's increased risk for psychopathology: For example, high maternal anxiety is associated with a twofold increase in the risk of probable mental disorder in children. We review several biological systems hypothesized to be mechanisms by which maternal distress affects fetal and child brain and behavior development, as well as the clinical implications of studies of the developmental origins of health and disease that focus on maternal distress. Development and parenting begin before birth.

Maternal prenatal stress phenotypes associate with fetal neurodevelopment and birth outcomes

“…Lack of social support during pregnancy is associated with poor birth outcomes as well as perinatal depression (44,(74)(75)(76)(77). Preclinical (78) and translational studies (79,80) indicate that social isolation hampers effective hypothalamic-pituitary-adrenal-axis regulation, reduces brain-derived neurotrophic factor expression, and amplifies proinflammatory processes identified at the molecular level-each potentially involved in maternal mental and physical health and contributing to offspring outcomes (81). From the perspective of solution-oriented research (82), these findings suggest that social support is a modifiable target for clinical engagement that could benefit women and their future children (83).…”

Positive Roles of Resveratrol in Early Development of Testicular Germ Cells against Maternal Restraint Stress in Mice

“…It is important to understand mechanisms such as altered placental activity, which allows more stress hormone cortisol to move through the fetus [43] and affects the essential role of the maternal immune system [44]. Faster physical development as well as more anxiety can be caused by prenatal stress in the neonate [45]. Here, we provided shreds of evidence that MRS across generations of timed pregnant mice has downstream impacts on germ cell development and testicular weight.…”

Cell-type specific impact of glucocorticoid receptor activation on the developing brain

“…This is because the concept of a dot-plot relies heavily on the absence of expression of a gene in all but a few cells. In order to ensure compatibility between combat-correction and dot plot visualisations of marker genes, we adjusted the expression matrix in the following way: (1) we computed the median expression of each gene after combat correction while excluding all values from the median calculation that were zero before combat correction; (2) we set all entries in the post-combat expression matrix to zero which were zero before combat correction and at the same time were below the previously computed median expression value of the respective gene. This way, we only allowed combat to activate the expression of genes if the combat-corrected expression value was above the median expression value of that gene.…”